Shin Nishio

Lenvatinib plus pembrolizumab in previously treated advanced endometrial cancer: 5-year outcomes from the randomized, phase 3 Study 309/KEYNOTE-775

Background In Study 309/KEYNOTE-775 ( NCT03517449 ), lenvatinib+pembrolizumab versus chemotherapy significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) in advanced endometrial cancer (EC). We report 5-year follow-up results. Methods Participants had advanced/recurrent/metastatic EC with progressive disease after one prior platinum-based chemotherapy regimen, measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), and no prior receipt of anti-programmed cell death protein 1 or anti-programmed cell death ligand 1 agents. Participants were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks or chemotherapy (doxorubicin or paclitaxel). Pembrolizumab was given for ≤35 cycles. Primary endpoints were OS and PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included ORR per RECIST v1.1 by BICR and safety. Efficacy endpoints were analyzed using Cox regression, Kaplan-Meier, and Miettinen and Nurminen methodology. Results 827 participants were randomized. At data cut-off (February 26, 2025), overall median follow-up was 68.8 months; 139 participants were alive (lenvatinib+pembrolizumab, n=86; chemotherapy, n=53), and all had ended their treatment in this study. Five-year OS rate was 16.7% with lenvatinib+pembrolizumab versus 7.3% with chemotherapy in mismatch repair-proficient EC, 36.5% versus 9.8% in mismatch repair-deficient EC, and 19.9% versus 7.7% in all-comers. Five-year PFS rates were 6.3% versus 2.1%, 26.4% versus 10.8%, and 9.8% versus 3.2%, respectively. In all-comers, treatment-related adverse events led to any treatment discontinuation in 32.3% versus 5.9%. Subsequent systemic anticancer therapy was used by 44.8% versus 51.2% (lenvatinib+pembrolizumab by 2.4% vs 10.1%). Conclusions Results were consistent with the primary analysis despite increased use of subsequent systemic anticancer therapy and crossover to lenvatinib+pembrolizumab in the chemotherapy group. The continued durable benefit, including OS, with lenvatinib+pembrolizumab and no new safety signals lend further support for this regimen as a standard of care therapy for EC.

Phase III double-blind randomized placebo controlled trial of atezolizumab in combination with carboplatin and paclitaxel in women with advanced/recurrent endometrial carcinoma: the Asian cohort of the AtTEnd/ENGOT-EN7 trial

This post-hoc analysis of the AtTEnd trial explored differences in the prognostic characteristics and in the efficacy of atezolizumab between Asians and non-Asians. The role of Asian race was evaluated on progression-free survival (PFS) using Cox-models and on time to appearance of new lesions using Fine and Gray models. From October 2018 to February 2022, 549 patients were randomized, of whom, 20.4% were Asian. Asians showed a better prognostic profile in terms of age, body mass index, Eastern Cooperative Oncology Group performance status, disease status and previous treatments. The prognostic impact of Asian race on PFS was confirmed in the placebo arm (adjusted hazard ratio [HR]=0.41; 95% confidence interval [CI]=0.24-0.70). In proficient mismatch repair (pMMR) tumors, the HRs for PFS comparing atezolizumab versus placebo were 0.82 (95% CI=0.63-1.05) in non-Asians, and 1.42 (95% CI=0.80-2.50) in Asians. In the pMMR population randomized to atezolizumab, the subdistribution HRs comparing Asians to non-Asians were 0.68 (95% CI=0.43-1.09) for progression with new lesions and 1.21 (95% CI=0.73-2.03) for progression without new lesions. Asians showed a higher occurrence of severe adverse events in atezolizumab compared to placebo arm (Asians: 82.1% vs. 64.3%, p=0.036; non-Asian: 63.3% vs. 63.6%, p=0.949). Race seems to affect the safety of the addition of atezolizumab and, in pMMR tumors, also its efficacy. In the atezolizumab arm, Asian patients seem to have a lower cumulative incidence of new lesions when primary tumor regrowth was considered a competing risk, and a higher cumulative incidence of primary tumor regrowth when new lesions appearance was the competing risk. ClinicalTrials.gov Identifier: NCT03603184.

Adjuvant Chemotherapy for Endometrial Cancer (ACE) trial: A randomized phase II study for advanced endometrial carcinoma

AbstractThis study evaluated the feasibility and efficacy of three postoperative adjuvant chemotherapy regimens for endometrial cancer. Endometrioid cancer patients with intermediate‐risk stage I and II or high‐risk stage III and IV disease were randomly assigned to receive six cycles of either paclitaxel‐epirubicin‐carboplatin (TEC), paclitaxel‐anthracycline (doxorubicin)‐carboplatin (TAC), or dose‐dense paclitaxel‐carboplatin (ddTC). The primary end‐point was the completion rate (CRate) of six cycles of treatment. The secondary end‐points were progression‐free survival (PFS) and overall survival (OS). One hundred and one patients were treated as follows: 33 received TEC, 33 TAC, and 35 ddTC. The CRates for TEC, TAC, and ddTC were 94%, 64%, and 69%, respectively (P = .005). The TEC CRate was significantly higher than for the other two groups. However, the PFS and OS outcomes were not statistically different between the three groups. The 2‐year survival rates were 94%, 97%, and 97% for TEC, TAC, and ddTC, respectively. When compared to the current standard treatments for endometrial cancer, TEC is a promising candidate for a phase III trial based on its significantly superior CRate and equivalent PFS and OS. This study is registered with UMIN Clinical Trials Registry (UMIN000008911).

A phase II, open-labeled, single-arm study of dose-dense paclitaxel plus carboplatin in advanced or recurrent uterine endometrial cancer treatment: a KCOG-G1303, DOENCA trial

To determine the safety and efficacy of dose-dense (dd) paclitaxel (PTX) and carboplatin (CBDCA) in treating advanced or recurrent endometrial cancer. Women aged 20-75 years with histologically confirmed endometrial cancer, the International Federation of Gynecology and Obstetrics (FIGO) stage III disease with some residual tumor, FIGO stage IV disease, recurrence after front-line curative treatment, or recurrence after second-line chemotherapy or radiotherapy were enrolled in this study. PTX (80 mg/m²) was administered intravenously (IV) to every participant on days 1, 8, and 15, and CBDCA (area under the curve of 5) was administered IV on day 1 once every 3 weeks until the disease progressed, unacceptable adverse events occurred, or consent was withdrawn. The primary endpoint was the response rate (RR), while the secondary endpoints were progression-free survival, overall survival, and adverse effects. Forty-eight participants were enrolled, and 46 were eligible to receive treatment. The patients' median age was 61 years (range, 43-76 years). Twenty-two participants had experienced recurrence, and the remaining patients had primary advanced endometrial cancer. There were 10 cases of serous carcinoma, 3 cases of endometrioid carcinoma G3, 2 cases of carcinosarcoma, and 2 cases of clear-cell carcinoma according to histology. Twenty-nine participants (63.0%) received ≥6 cycles of chemotherapy. The RR (complete, 13 cases; partial, 20 cases) was 71.3% (95% confidence interval: 59.0%-84.5%). The dd PTX with CBDCA is feasible and available as a treatment option for advanced or recurrent endometrial cancer. UMIN Clinical Trials Registry Identifier: UMIN000017138.

Subcategorization of atypical glandular cells is useful to identify lesion site

AbstractBackgroundIn the subcategorization of atypical glandular cells (AGCs), origin of cells should be mentioned to estimate lesion sites for diagnosis. However, cases without subcategorization are often encountered due to limited reproducibility. We evaluated whether the subcategorization of AGC based on the Bethesda terminology can estimate lesion sites.MethodsWe retrospectively investigated cases whose cervical smears were interpreted as AGC and underwent pathological assessment at our institution between June 2009 and September 2017. AGC was subcategorized based on the Bethesda System. Not‐otherwise‐specified (NOS) was subcategorized into endocervical cells (NOS‐EC), endometrial cells (NOS‐EM), or glandular cells (NOS‐G). Favor neoplastic (FN) was subcategorized into endocervical cells (FN‐EC) or glandular cells (FN‐G). FN‐G was further subcategorized into endometrial cells (FN‐EM) or unknown origin (FN‐UO). Clinicopathological data were retrieved from the medical records.ResultsOf 88 AGC cases, there were 30 NOS‐EC (34.1%), 2 NOS‐EM (2.3%), 25 FN‐EC (28.4%), 22 FN‐EM (25.0%), and 9 FN‐UO (10.2%). A significantly higher proportion of neoplastic lesions occurred in FN than in NOS (P <.001). The concordance of AGC subclass and lesion site was 88.0%, 70.7%, and 77.3% in FN‐EC, FN‐G, and FN‐EM, respectively. The concordance of FN‐EM and lesion site increased to 88.9% in patients aged >50 years. Of nine cases of FN‐UO, six experienced nonendometrioid endometrial cancer and extrauterine malignancy.ConclusionSubcategorization of NOS and FN would be useful in estimating neoplastic lesions. Further subcategorization into FN‐EC, FN‐EM, and FN‐UO would similarly be beneficial in estimating the lesion site, especially for small endometrial and extrauterine lesions.

A new hyaluronate gel spacer and injection technique for cervical cancer brachytherapy: a technical report

Abstract Spacers separating the tumor from adjacent organs help improve irradiation dose parameters. We introduce a new hyaluronate gel spacer with MEIJI (ADANT®) as an alternative to the previously used Suvenyl® and its injection technique for cervical cancer brachytherapy. Five patients with cervical cancer underwent hyaluronate gel injection (HGI) with the MEIJI hyaluronate gel in their rectovaginal and vesicovaginal septa. The minimum doses covering 90% of the high-risk clinical target volume (CTVHRD90%), the most exposed 2 cc (D2cc) of organs at risk per session, as well as the total doses for combined external beam radiotherapy (with a central shield) and brachytherapy, were assessed. The median CTVHRD90% was 9.3 (range, 6.4–9.7) Gy per session and 92.2 Gy in the equivalent dose in 2 Gy fractions (EQD2) (80.3–93.3 Gy-EQD2) overall. The median rectum D2cc was 2.9 (1.8–5.0) Gy per session and 45.4 (43.4–57.1) Gy-EQD2 overall. The median D2cc of the bladder (bladder D2cc) was 4.8 (2.4–6.5) Gy per session and 64.6 (62.3–69.6) Gy-EQD2 overall. The MEIJI spacer disappeared within 3 or 7 days with no adverse events associated with HGI or deterioration of the patients’ quality of life. MEIJI HGI facilitates a sufficient CTVHRD90% while keeping the rectal and bladder D2cc within dose constraints, even when the rectum and bladder are in close proximity to the CTVHR. In conclusion, the MEIJI spacer may help appropriately meet dose constraints, thereby potentially contributing to improving local control and/or reducing adverse events for patients receiving radiotherapy for cervical cancer.

Efficacy of Rikkunshito on Chemotherapy-Induced Nausea and Vomiting in Patients With Uterine Corpus or Cervical Cancer Treated With Cisplatin-Based Regimen-Placebo-controlled, Double-Blind, Randomized Confirmatory Study (JORTC-KMP03)

Background: The current standard treatment for chemotherapy-induced nausea and vomiting (CINV) with standard antiemetics is insufficient. Rikkunshito, a Japanese traditional herbal medicine, has been shown to improve cisplatin-induced anorexia and functional dyspepsia, and our exploratory study found that rikkunshito has an additive beneficial effect on CINV in patients with uterine corpus and cervical cancer receiving cisplatin containing chemotherapy (JORTC KMP-02). Methods: One hundred eighty patients with uterine corpus or cervical cancer who were scheduled to receive treatment with a cisplatin based regimen as initial chemotherapy were enrolled across 17 Japanese institutions. Patients were randomized with a 1:1 equal allocation ratio to the rikkunshito group or placebo groups and given oral administration on days 1 to 5 with standard antiemetics (granisetron, aprepitant, and dexamethasone). The primary endpoint was complete response (CR; no vomiting or rescue medication) during the delayed phase (24-120 hours after cisplatin treatment). The secondary endpoints were complete control (CC; CR without significant nausea) and total control (TC; CR without nausea) rates during the overall (0-120 hours), acute (0-24 hours), and delayed phases, as well as the CR rate during the overall and acute phases, time to treatment failure, degree of nausea and appetite during the overall phase, and adherence to the intervention. Results: The CR rate in the delayed phase was similar between the rikkunshito group and control groups (50.6% vs 58.9%, P  = .2631), as were the secondary endpoints: CR rates in the overall and acute phases, CC and TC rates in the overall, acute, and delayed phases, degrees of nausea and appetite, and time to treatment failure. Conclusion: Rikkunshito had no additive effect on CINV prevention in patients with uterine corpus or cervical cancer who were treated with a cisplatin based regimen and standard antiemetics. Clinical Trial Registration: https://jrct.mhlw.go.jp/re/reports/detail/66957 , identifier jRCT1011190007

Tegafur-uracil maintenance chemotherapy post-chemoradiotherapy for cervical cancer: Randomized trial

Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer (LACC), but recurrence rates remain high. This multicenter phase-3 randomized trial (GOTIC-002) evaluated the efficacy of low-dose oral tegafur-uracil (UFT) as maintenance chemotherapy following curative CCRT for LACC. Between 2010 and 2018, 351 patients with stage Ib2-IVa cervical cancer were enrolled. After achieving complete or partial remission post-CCRT, patients were randomized 1:1 into observation (arm O) or UFT maintenance therapy (arm UFT). UFT doses were 300-400 mg/day based on body surface area for 2 years, disease progression or adverse effects occurred. The primary endpoint was progression-free survival (PFS), with overall survival (OS) and safety as secondary endpoints. Patient characteristics were similar between the groups (n = 178 in arm O, n = 173 in arm UFT). During a median follow-up of 3 years, median PFS was not reached in either group. 5-year PFS rates were similar between them (arm O: 61.3 %, arm UFT: 62.0 %, hazard ratio: 0.92, P = .634). 5-year OS rates were also comparable (77.6 % vs 76.1 %, hazard ratio: 1.04, P = .869). Compliance with UFT ranged from 87.8 % to 98.8 %. Although adverse events were more frequent in arm UFT (93.5 % vs 73.9 %, odds ratio: 5.05), most were mild or moderate. Despite its tolerability, UFT did not improve PFS or OS. These findings suggest the need to reconsider maintenance therapy strategies after CCRT for potentially shifting away from cytotoxic chemotherapy towards alternative methods to enhance survival outcomes in patients with LACC.

Treatment specialty‐specific characteristics and outcomes in women with vulvo‐vaginal melanoma: A JGOG‐JSCS joint study

Clinical outcomes and prognostic factors of adjuvant radiotherapy for vulvar cancer: a Japanese Gynecologic Oncology Group nationwide survey study

Abstract This study aimed to analyze the clinical outcomes and prognostic factors of postoperative adjuvant radiotherapy (RT) for vulvar cancer based on a retrospective Japanese nationwide survey. Data were collected from 108 institutions for patients diagnosed with vulvar cancer between January 2001 and December 2010. Patients with histologically confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma who underwent curative surgery and adjuvant radiotherapy were included in this study. Survival outcomes were estimated using the Kaplan–Meier method, and prognostic factors were analyzed via univariate and multivariate models. A total of 139 patients were included, with a median follow-up of 44 months (range: 3–169). The 5-year overall survival (OS) rates (95% confidence interval [CI]) for stages I, II, III, and IV were 71.8% (50.8–92.8%), 61.3% (40.1–82.5%), 58.0% (45.8–70.2%), and 47.3% (27.5–67.1%), respectively. The corresponding 5-year cause-specific survival (CSS) rates (95% CI) for stages I, II, III, and IV were 71.8% (50.8–92.8%), 73.4% (53.0–93.8%), 62.2% (50.0–74.4%), and 47.3% (27.5–67.1%). Multivariate analysis identified age ≥70 years as an independent adverse prognostic factor for OS (hazard ratio [HR]: 1.848; 95% CI: 1.039–3.281; P = 0.042), while the presence of ≥2 inguinofemoral lymph node metastases was significantly associated with poorer CSS (HR: 2.179; 95% CI: 1.109–4.280; P = 0.030). Our analysis identified advanced age and a higher nodal burden as significant predictors of poorer survival outcomes in patients with vulvar cancer receiving postoperative adjuvant RT.

Significance of definitive concurrent chemoradiotherapy for vulvar cancer: a Japanese Gynecologic Oncology Group nationwide survey study

Abstract Objective This study aimed to show the results of radical radiation therapy (RT) and concurrent chemoradiotherapy (CCRT) for vulvar cancer (VC) based on data from a Japanese nationwide survey. Materials and methods We collected data from 108 institutions on cases of VC diagnosed between January 2001 and December 2010. Patients with histologically proven squamous cell carcinoma and adenocarcinoma with curative intent were selected, and 172 patients with VC were included in this study. The collected data were analyzed for overall survival (OS) using the Kaplan–Meier method. Univariate and multivariate analyses were performed to examine the prognostic factors for patients with VC. Results The median follow-up period was 16.8 (range; 3.2–154.8) months. Fifty-five patients received CCRT, and 117 patients received RT alone. The 2-year OS rates (95% confidence interval [CI]) for stages I, II, III, and IV were 77.9% (55.8–100.0), 71.9% (53.8–89.9), 55.4% (42.5–68.3), and 41.5% (27.3–55.7) respectively. Univariate analyses showed that the FIGO stage (p = 0.001), tumor diameter (p = 0.005), and lymph node (LN) status (p = 0.001) were associated with OS. The concurrent use of chemotherapy resulted in a significantly longer OS in Stage III (p = 0.013). Multivariate analysis showed that the hazard ratios (95% CI) for tumor diameter, positivity for LN metastasis, and RT alone (no concurrent chemotherapy) were 1.502 (1.116–2.021), 1.801 (1.287–2.521), and 1.936 (1.187–3.159), respectively. Conclusions Our analysis revealed that CCRT should be recommended, especially for Stage III VC patients. Further studies are warranted to determine who benefits from CCRT, considering primary tumor size and LN status. The study was registered at the University Hospital Medical Information Network (protocol number: UMIN000017080) on April 8th, 2015.

Current status of vulvar cancer in Japan: analysis of the Japanese Gynecologic Oncology Group nationwide survey study

Abstract This review provides an overview of the current status of vulvar cancer in Japan, focusing specifically on the findings from the Japanese Gynecologic Oncology Group nationwide survey study. The author offers a comprehensive summary of the current status of vulvar cancer in Japan, along with an exploration of the molecular mechanisms underlying the disease. Notably, the review highlights the concerning upward trend of vulvar cancer in older age groups and advanced stages in Japan. The author concludes that addressing these challenges may require the centralization of resources and expertise. By bridging knowledge gaps and identifying areas for improvement, this review contributes to enhancing the understanding and management of vulvar cancer in Japan.

Validation of the 2021 FIGO staging schema for advanced vulvar cancer

The International Federation of Gynecology and Obstetrics (FIGO) revised the vulvar cancer staging schema in 2021. Previous stage IIIA-B diseases were reclassified based on nodal size (≤5 mm for stage IIIA compared with >5 mm for stage IIIB), and previous stage IVA1 disease based on non-osseous organ extension was reclassified to stage IIIA whereas osseous extension remained as stage IVA. This study sought to validate the 2021 FIGO vulvar cancer staging schema. This retrospective cohort study examined 889 women with stage III-IV vulvar cancer from 2010 to 2015 in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Stage shift and overall survival were assessed by comparing the 2021 and 2009 FIGO staging schemas. Stage shift occurred in 229 (25.8%) patients (upstaged 17.7% and downstaged 8.1%). When comparing the new and previous staging schemas, 5 year overall survival rates were 45.6% versus 48.9% for stage IIIA, 47.0% versus 44.2% for stage IIIB, and 13.9% versus 25.1% (interval change -11.2%) for stage IVA diseases. According to the revised staging schema, 5 year overall survival rates were similar for stage IVA and IVB diseases (13.9% vs 14.5%) and for stage IIIA and IIIB disease (45.6% vs 47.0%). For new stage IIIA disease, 5 year overall survival rates differed significantly based on the staging factors (nodal involvement vs non-nodal organ involvement, 48.9% vs 38.7%, difference 10.2%, p=0.038). The 2021 FIGO staging schema results in one in four cases of advanced vulvar cancer being reclassified. Survival rates of patients with new stage IVA disease worsened significantly whereas those of patients with new stage IIIA disease were heterogenous based on the staging factors. The discriminatory ability of the revised 2021 FIGO staging schema for 5 year overall survival rate between patients with stage IIIA and IIIB tumors and those with IVA and IVB tumors is limited in this study population.

Characteristics and outcomes of women with adenocarcinoma versus squamous cell carcinoma of the vulva: A Japanese Gynecologic Oncology Group study

Studies on vulvar adenocarcinoma are lacking. Thus, we aimed to compare the characteristics and survival outcomes between vulvar adenocarcinoma and squamous cell carcinoma (SCC). This was a preplanned sub-analysis of a previously organized nationwide retrospective observational study in Japan conducted between 2001 and 2010 (JGOG-1075S). Surgically treated women with stage I-IV vulvar invasive adenocarcinoma were compared to those with SCC. Multivariable analysis was performed to identify patient and tumor characteristics related to adenocarcinoma. Inverse probability of treatment weighting was used to balance the background differences, and a Cox proportional hazards regression model was fitted to estimate the effect of the histological type on survival. Forty-eight women with adenocarcinoma were compared with 537 women with SCC. On multivariable analysis, women with adenocarcinoma were younger (median age, 64.5 vs. 70 years, adjusted odds ratio [OR] per age 0.975, 95% confidence interval [CI] 0.955-0.995, P = 0.016) and had higher positive surgical margin rates (31.2% vs. 18.4%, adjusted OR 2.376, 95% CI 1.188-4.754, P = 0.014) than those with SCC. However, according to the weighted model, the survival outcomes were comparable (hazard ratio for progression-free survival, 1.088, 95% CI 0.740-1.601, P = 0.667 and hazard ratio for overall survival, 1.008, 95% CI 0.646-1.573, P = 0.973). Similar associations were observed when the cohort was stratified by age (≤70 or >70 years), stage (I-II or III-IV), and surgical margin (negative or positive) (all, P > 0.05). Vulvar adenocarcinoma is characterized by a younger age at diagnosis and higher positive surgical margin rates than SCC, but the survival outcomes are comparable.

A randomized phase III trial of adjuvant chemotherapy versus concurrent chemoradiotherapy for postoperative cervical cancer: Japanese Gynecologic Oncology Group study (JGOG1082)

The standard treatment for stage IB-IIB cervical cancer is radiotherapy or radical hysterectomy; after radical hysterectomy, adjuvant concurrent chemoradiotherapy is recommended for patients with high risk factors. However, adjuvant concurrent chemoradiotherapy can cause severe gastrointestinal and urinary toxicity. To assess whether postoperative adjuvant chemotherapy is not inferior to adjuvant concurrent chemoradiotherapy for overall survival in patients with high risk cervical cancer. Adjuvant chemotherapy is not inferior to adjuvant concurrent chemoradiotherapy for overall survival and will reduce severe toxicities. Patients with high risk factors after radical hysterectomy will be randomized 1:1 to receive adjuvant concurrent chemoradiotherapy or adjuvant chemotherapy. Treatment will be started within 6 weeks of surgery. The concurrent chemoradiotherapy group will receive whole pelvis irradiation (50.4 Gy) and cisplatin (40 mg/m Patients with high risk stage IB-IIB cervical cancer (squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma) who underwent radical hysterectomy are eligible for the study. High risk is defined as the presence of pelvic lymph node metastasis and/or parametrial invasion. The primary endpoint is overall survival. 250 patients in total are required. This study began in November 2019, and 250 patients will be accrued within 5 years. The study has been registered with the Japan Registry of Clinical Trials (jRCTs041190042).

Pembrolizumab plus chemotherapy in Japanese patients with persistent, recurrent or metastatic cervical cancer: Results from KEYNOTE‐826

AbstractPembrolizumab plus chemotherapy with or without bevacizumab demonstrated prolonged progression‐free survival (PFS) and overall survival (OS) versus chemotherapy in patients with persistent, recurrent, or metastatic cervical cancer in the phase 3, randomized, double‐blind, placebo‐controlled KEYNOTE‐826 study. We report outcomes in patients enrolled in Japan. Patients received pembrolizumab 200 mg or placebo Q3W for up to 35 cycles plus chemotherapy (paclitaxel 175 mg/m2 + cisplatin 50 mg/m2 or carboplatin AUC 5) with or without bevacizumab 15 mg/kg. Dual primary endpoints were PFS per RECIST v1.1 by investigator assessment and OS in the global population; these were evaluated in patients with tumors with PD‐L1 combined positive score (CPS) ≥1, all‐comers, and PD‐L1 CPS ≥10. Fifty‐seven patients from Japan were randomized (pembrolizumab plus chemotherapy, n = 35; placebo plus chemotherapy, n = 22). Pembrolizumab plus chemotherapy improved PFS versus placebo plus chemotherapy in patients with PD‐L1 CPS ≥1 (n = 51; hazard ratio [HR; 95% CI], 0.36 [0.16–0.77]), all‐comers (n = 57; 0.45 [0.22–0.90]), and patients with PD‐L1 CPS ≥10 (n = 25; 0.36 [0.12–1.07]). HRs (95% CI) for OS were 0.38 (0.14–1.01), 0.41 (0.17–1.00), and 0.37 (0.10–1.30), respectively. Incidence of grade 3–5 AEs was 94% in the pembrolizumab group and 100% in the placebo group. Consistent with findings in the global KEYNOTE‐826 study, pembrolizumab plus chemotherapy with or without bevacizumab may prolong survival versus placebo plus chemotherapy with or without bevacizumab and had a manageable safety profile in Japanese patients with persistent, recurrent, or metastatic cervical cancer.

Analysis of postoperative adjuvant therapy in 102 patients with gastric-type mucinous carcinoma of the uterine cervix: A multi-institutional study

Gastric-type mucinous carcinoma (GAS) is a novel variant of uterine cervix mucinous carcinoma. GAS is a distinct entity that can be distinguished from typical endocervical adenocarcinoma (UEA). In Japan, postoperative adjuvant therapy for cervical cancer includes not only radiation therapy (RT) or concurrent chemoradiotherapy (CCRT) but also chemotherapy in many cases. However, no previous studies have analyzed adjuvant therapy for GAS. In the present study, we investigated the efficacy of adjuvant therapy for GAS. This was a preplanned secondary analysis of a dataset from previous nationwide, retrospective, observational study. The study population comprised women with stage I-II GAS who underwent surgery. Progression-free survival (PFS) and overall survival (OS) were compared among patients who did and did not receive adjuvant therapy using the Kaplan-Meier method. Data were analyzed for a total of 102 enrolled patients, who were classified as low- (17 patients), intermediate- (37 patients), or high risk (48 patients) based on the risk of postoperative cervical cancer recurrence. In the intermediate-risk group, median survival could not be assessed due to a lack of sufficient events, but the no-adjuvant and RT groups tended to exhibit better prognoses. In contrast, within the high-risk group, patients in the RT subgroup exhibited a trend towards better PFS and OS than those in the CCRT and chemotherapy groups. The prognosis of GAS was confirmed to be poor, even in cases of early-stage cancer and following surgical resection. Chemotherapy strategies, including CCRT as postoperative adjuvant therapy, tend to have a poor prognosis.

A survey of carboplatin desensitization therapy in Japan: A multicenter retrospective study

AbstractIntroductionHypersensitivity reactions (HSRs) to chemotherapy are serious adverse events associated with cancer drug therapy and can occur with any antitumor drug. This study investigated the safety and efficacy of carboplatin desensitization therapy in Japan and established a method for treating carboplatin HSRs.MethodsPatients diagnosed with gynecological (ovarian, endometrial, or cervical) cancers who underwent carboplatin desensitization therapy between 2016 and 2020 at the Gynecologic Cancer Study Group of Japan Clinical Oncology Group were included. The carboplatin desensitization therapy at each institution and the implementation cases were registered in an online case report form.ResultsThis retrospective study enrolled 136 patients (ovarian, 108; endometrial, 17; and cervical cancer, 11). Pre‐existing allergies were present in 37 (27.2%) patients, and 32 (23.5%) patients exhibited prodromal symptoms during treatment before HSR onset. Erythema was the most common symptom at HSR onset, affecting 93 (68.4%) patients, followed by itching in 72 (52.9%) patients and decreased oxygen saturation in 43 (31.6%) patients. Loss of consciousness occurred in three (2.2%) patients. The most common timing of HSR onset was during the first recurrence treatment (47%). The mean total carboplatin dose until HSR onset was 7331 (2620–18,282) mg, and the mean number of doses was 14 (4–63). Desensitization treatment was completed in 75% of cases, and breakthrough HSRs occurred in 25% (34/136). No deaths occurred in the study cohort. The risk factors for HSRs were not identified.ConclusionAlthough carboplatin desensitization therapy has high success rates in Japan, erythema and pruritus are important HSRs to consider.

Durvalumab with carboplatin/paclitaxel and bevacizumab followed by durvalumab and bevacizumab with or without olaparib maintenance in newly diagnosed non-BRCA-mutated advanced ovarian cancer

Despite treatment advances in newly diagnosed advanced-stage ovarian cancer (aOC), improved outcomes are needed. DUO-O (NCT03737643), a phase III placebo-controlled trial, enrolled patients with newly diagnosed aOC. Following one cycle of carboplatin/paclitaxel ± bevacizumab, patients without a tumor BRCA mutation (non-tBRCAm) were randomly assigned (1 : 1 : 1) at cycle 2 to carboplatin/paclitaxel plus bevacizumab followed by bevacizumab (control); carboplatin/paclitaxel, bevacizumab plus durvalumab followed by bevacizumab plus durvalumab (durvalumab arm); or carboplatin/paclitaxel, bevacizumab plus durvalumab followed by bevacizumab, durvalumab plus olaparib (durvalumab + olaparib arm). Investigator-assessed progression-free survival (PFS; primary endpoint) was tested for the durvalumab + olaparib arm versus control in the non-tBRCAm homologous recombination deficiency (HRD)-positive and non-tBRCAm intention-to-treat (ITT) populations. One thousand one hundred and thirty patients were randomly allocated to the study. The prespecified interim PFS analysis [data cut-off (DCO): 5 December 2022] qualified as the primary analysis; PFS hazard ratio (HR) for the durvalumab + olaparib arm versus control was 0.49 [95% confidence interval (CI) 0.34-0.69, P < 0.0001; median (m) PFS 37.3 versus 23.0 months] in the non-tBRCAm HRD-positive and 0.63 (95% CI 0.52-0.76, P < 0.0001; mPFS 24.2 versus 19.3 months) in the non-tBRCAm ITT population. For the durvalumab arm versus control, PFS HR was 0.87 (95% CI 0.73-1.04, P = 0.13; mPFS 20.6 versus 19.3 months) in the non-tBRCAm ITT population. At final PFS and interim overall survival (OS) analysis (DCO: 18 September 2023), PFS results were consistent with primary analysis; interim OS HR for the durvalumab + olaparib arm versus control was 0.95 (95% CI 0.76-1.20, P = 0.68; 39.0% maturity) in the non-tBRCAm ITT population. Safety was generally consistent with the profiles of the individual agents. DUO-O met its primary PFS endpoints for first-line durvalumab plus carboplatin/paclitaxel and bevacizumab followed by durvalumab, bevacizumab plus olaparib maintenance versus carboplatin/paclitaxel and bevacizumab followed by bevacizumab in the non-tBRCAm HRD-positive and non-tBRCAm ITT populations. Further insight into long-term benefit is anticipated with additional follow-up.

Atezolizumab, bevacizumab, and platinum chemotherapy in cervical cancer: results of Japanese population from BEATcc

This study analyzed the efficacy of add-on atezolizumab to standard first-line bevacizumab-containing therapy in 56 Japanese patients with metastatic and recurrent cervical cancer treated across 8 sites under the Japanese Gynecologic Oncology Group between October 2018 and August 2021 in the BEATcc trial. Patients were randomized to standard arm (standard therapy: cisplatin 50 mg/m² or carboplatin area under the curve of 5, paclitaxel 175 mg/m², and bevacizumab 15 mg/kg) or experimental arm (standard therapy with atezolizumab 1,200 mg). Of 56 patients, 30 were in experimental arm vs. 26, standard arm (age: 53.2±12.9 vs. 54.7±12.2 years). Median progression-free survival was 15.8 months (95% confidence interval [CI]=10.4-26.1) in experimental arm vs. 11.1 months (8.4-16.5) in standard arm (hazard ratio [HR]=0.51; 95% CI=0.26-1.01). Median overall survival was 34.1 months (23.2-38.6) in the experimental arm vs. 31.6 months (16.4-36.5), standard arm (HR=0.53; 95% CI=0.23-1.21). Objective response rate was 86.7% in experimental arm vs. 84.6%, standard arm. Complete response and partial response, respectively, were 23.3% and 63.3% in experimental arm and 26.9% and 57.7% in standard arm. Grade ≥3 adverse events occurred in 80.0%, experimental arm and 88.5%, standard arm. Gastrointestinal/genitourinary fistula incidence was lower in Japanese patients (1 patient receiving atezolizumab), likely due to stricter inclusion criteria. Overall, add-on atezolizumab enhances the efficacy of bevacizumab and chemotherapy in Japanese patients as those in overall BEATcc population and could be considered a new first-line treatment option for metastatic, persistent, or recurrent cervical cancer in Japan. ClinicalTrials.gov Identifier: NCT03556839.

Pembrolizumab plus chemotherapy with or without bevacizumab in East Asian participants with persistent, recurrent, or metastatic cervical cancer: results from KEYNOTE-826 final analysis

In the phase 3 KEYNOTE-826 study (NCT03635567), pembrolizumab plus chemotherapy with or without bevacizumab significantly improved progression-free survival (PFS) and overall survival (OS) in participants with persistent, recurrent, or metastatic cervical cancer. We report an exploratory analysis of outcomes for participants enrolled in East Asia based on the final analysis of KEYNOTE-826. Participants were randomized 1:1 to receive pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles. All participants received chemotherapy with paclitaxel and cisplatin or carboplatin for up to 6 cycles, and optionally received bevacizumab at the investigator's discretion. PFS and OS were dual primary endpoints. Ninety-seven participants from East Asia were enrolled in the intention-to-treat population. At data cutoff (October 3, 2022), in the intention-to-treat population, median PFS in the pembrolizumab plus chemotherapy and placebo plus chemotherapy groups was 18.0 and 10.4 months, respectively (hazard ratio [HR]=0.42; 95% confidence interval [CI]=0.23-0.77); median OS was not reached and 20.4 months, respectively (HR=0.53; 95% CI=0.28-0.99). In the programmed cell death ligand 1 combined positive score (CPS) ≥1 population, median PFS was 29.3 and 10.9 months, respectively (HR=0.36; 95% CI=0.19-0.68); median OS was not reached and 17.4 months, respectively (HR=0.43; 95% CI=0.22-0.86). The most common adverse events with pembrolizumab plus chemotherapy versus placebo plus chemotherapy were alopecia (75% vs. 68%) and anemia (67% vs. 65%). These data support the use of pembrolizumab plus chemotherapy with or without bevacizumab for the treatment of persistent, recurrent, or metastatic cervical cancer in East Asian patients. ClinicalTrials.gov Identifier: NCT03635567.

Durvalumab plus carboplatin/paclitaxel followed by durvalumab with or without olaparib as first-line treatment for newly diagnosed advanced or recurrent endometrial cancer: Japan subset from the phase III DUO-E trial

DUO-E/GOG-3041/ENGOT-EN10 (NCT04269200) demonstrated statistically significant and clinically meaningful progression-free survival (PFS) improvement with durvalumab plus carboplatin/paclitaxel, followed by durvalumab with or without olaparib, vs. carboplatin/paclitaxel alone (intention-to-treat [ITT] population) in patients with newly diagnosed advanced or recurrent endometrial cancer. We evaluated efficacy and safety in the Japan subset of DUO-E. Patients with newly diagnosed International Federation of Gynecology and Obstetrics stage III/IV or recurrent endometrial cancer were randomized 1:1:1 to control arm (carboplatin/paclitaxel + durvalumab placebo [6 cycles] followed by durvalumab placebo + olaparib placebo), durvalumab arm (carboplatin/paclitaxel + durvalumab [1,120 mg every 3 weeks] [6 cycles] followed by durvalumab [1,500 mg every 4 weeks] + olaparib placebo), or durvalumab + olaparib arm (carboplatin/paclitaxel + durvalumab [6 cycles] followed by durvalumab + olaparib [300 mg twice a day]). Dual primary endpoints were investigator-assessed PFS for durvalumab and durvalumab + olaparib arms vs. control. This prespecified exploratory analysis evaluated PFS and safety in the Japan subset. In the Japan subset (n=88) PFS favored durvalumab (hazard ratio=0.61, 95% confidence interval [CI]=0.32-1.12) and durvalumab + olaparib (0.44, 95% CI=0.22-0.85) vs. control; median PFS was 9.9 and 15.1 vs. 9.5 months, and the 18-month PFS rate was 37.0% and 42.1% vs. 22.2%, respectively. The safety profile in the Japan subset was generally consistent with the full safety analysis set and the established profiles of the individual agents. Efficacy and safety in the Japan subset were generally consistent with outcomes in the DUO-E ITT population. This Japanese subset analysis of DUO-E supports carboplatin/paclitaxel + durvalumab followed by durvalumab with or without olaparib as new treatment options in patients with advanced or recurrent endometrial cancer and is the first to report on these regimens in Japanese patients alone.

Diagnostic accuracy and prognostic factors of uterine serous carcinoma in Japanese women: a multi-center study

This multi-center retrospective study aimed to clarify the characteristics, diagnostic accuracy, treatment outcomes, and prognostic factors of uterine serous carcinoma (USC) in Japanese women. The medical records of 193 patients who were treated between 2006 and 2008 at 24 participating institutions in the Japanese Clinical Oncology Group were examined, and pathological slides of 188 patients were re-checked through central pathology review (CPR), hematoxylin-eosin staining, and immunohistochemistry. USC was confirmed in 144 of the 188 (76.6%) patients using CPR, and only 50% were correctly diagnosed preoperatively. Forty-three patients were diagnosed with non-serous carcinoma, whereas one patient had metastasis from another organ. The average age was 65.7 years, and 19% of patients had a history of other cancers. The incidence of stage III-IV disease was 52.8%, and lymph node metastasis was found in 28.5% of patients. Extrauterine spread and distant metastasis occurred in 39% and 14% of patients, respectively. The 2-year overall survival and progression-free survival (PFS) rates were 56% and 42%, respectively. The PFS of patients with stage I and II who underwent complete staging surgery was 92.3%, and that of those without lymph node dissection or omentectomy was 33.3%. Patients with USC had a significantly worse prognosis than 43 patients with non-serous carcinoma. USC in Japanese women has characteristics different from those of endometrioid carcinoma, worse prognosis, and is difficult to diagnose preoperatively. Complete surgical staging is necessary even for early-stage disease. Additionally, new adjuvant treatment strategies, including molecular targeted therapy, should be explored.

Pharmacokinetic and Exposure–Response Modeling Support Body Surface Area‐Based Dosing of Farletuzumab Ecteribulin in Japanese Patients with Solid Tumors

AbstractThe first‐in‐human, Phase 1 Study 101 showed antitumor activity and a tolerable safety profile of farletuzumab ecteribulin in Japanese patients with platinum‐resistant ovarian and non‐small cell lung cancer. A pharmacometric assessment evaluated farletuzumab ecteribulin pharmacokinetics and exposure–response (E‐R) relationships for efficacy and safety to support dose optimization. Patients received 0.3‐1.2 mg/kg of farletuzumab ecteribulin intravenously every 3 weeks. A pharmacokinetics (PK) model was developed and used for E‐R analyses. Efficacy was assessed via tumor response and safety via known treatment‐emergent adverse events (TEAEs) of farletuzumab ecteribulin, particularly pneumonitis/interstitial lung disease (ILD). Dosing scenarios were simulated to identify dosing that maximizes the probability of an objective response while minimizing the risk of ILD. The farletuzumab ecteribulin PK dataset included 1261 observations from 82 patients. The final model included an estimated population mean value for farletuzumab ecteribulin clearance of 0.0162 L/h. Body surface area (BSA) was a significant PK covariate and was included in the model. Body weight (BW) was associated with higher farletuzumab ecteribulin exposure. Using BW‐based dosing, farletuzumab ecteribulin AUC (area under the serum concentration–time curve) was higher in patients with tumor response or stable disease versus patients with progressive disease and higher in patients with ILD and other TEAEs. Dosing simulations showed that BSA‐based dosing (33 mg/m2) yielded similar tumor responses to BW‐based dosing (0.9 mg/kg) and decreased ILD rates. This study showed that BW‐based dosing resulted in higher risks of ILD events for patients with a high BW versus low BW, whereas BSA‐based dosing is predicted to reduce this risk while maintaining clinical efficacy.

Niraparib in Japanese patients with platinum-sensitive recurrent ovarian cancer: final results of a multicenter phase 2 study

This study evaluated the long-term safety and efficacy of niraparib in Japanese patients with platinum-sensitive recurrent ovarian cancer. This was a follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with platinum-sensitive, relapsed ovarian cancer. Participants received niraparib (starting dose 300 mg) once daily in continuous 28-day cycles. The primary endpoint was the incidence of Grade 3 or 4 thrombocytopenia-related events (defined as the overall incidence of the MedDRA Preferred Terms "thrombocytopenia" and "platelet count decreased") occurring in the 30 days after initial administration of niraparib, and secondary endpoints included evaluation of treatment-emergent adverse events and progression-free survival. Nineteen patients (median age, 62 years; median body weight, 53.9 kg) were enrolled. As previously reported, the incidence of Grade 3 or 4 thrombocytopenia-related events during the first 30 days of treatment was 31.6%. At data cutoff, median (range) treatment exposure was 504.0 (56-1,054) days and mean ± standard deviation dose intensity was 154.4±77.5 mg/day. The most common treatment-emergent adverse events were nausea (n=14, 73.7%), decreased platelet count (n=12, 63.2%), decreased neutrophil count (n=11, 57.9%), anemia, vomiting, and decreased appetite (all n=9, 47.4%). One patient was diagnosed with treatment-related leukemia, which resulted in death. Median (95% confidence interval) progression-free survival was 18.0 (5.6-26.7) months. Overall, the safety profile of niraparib was considered manageable in this study population of Japanese patients with platinum-sensitive, relapsed ovarian cancer and was consistent with that observed in studies of non-Japanese patients. ClinicalTrials.gov Identifier: NCT03759587.

Olaparib maintenance therapy for platinum‐sensitive relapsed ovarian cancer at a single institution: A retrospective study

Abstract Aim In this study, we aimed to investigate patient characteristics, efficacy, prognostic factors, and safety of olaparib maintenance therapy for platinum‐sensitive recurrent ovarian cancer at our institution. Methods Patients responding to platinum‐based therapy and starting olaparib maintenance therapy for recurrent epithelial ovarian, fallopian tube, or peritoneal cancer at Kurume University Hospital between January 2018 and November 2021 were enrolled in the study. Their data were extracted retrospectively from medical records. Results In all, 50 patients were included. The median (range) age of the patients, follow‐up time, and duration of olaparib maintenance therapy were 62 (39–87) years, 21.6 (2.2–45.9) months, and 7.2 (2–45.9) months, respectively. Among the 29 patients tested for homologous recombination (HR) status, 22 (75.9%) were positive for HR deficiency (HRD), 12 (54.5%) of whom had BRCA ‐positive tumors. The median progression‐free survival was 8.9 months (95% confidence interval: 6.2–12.6), and the median overall survival was 27.1 months (95% confidence interval: 22.5–40.3). Multivariate analysis of prognostic factors revealed that HRD was an independent prognostic factor for both progression‐free survival and overall survival. The most common adverse event was nausea (any grade, n  = 30, 60%), resulting in drug interruption ( n  = 23, 46%), dose reduction ( n  = 17, 34%), and discontinuation of treatment ( n  = 1, 2%). Conclusion Olaparib maintenance therapy for recurrent platinum‐sensitive ovarian cancer at our institution was effective, with acceptable adverse events. HRD was the most significant prognostic factor for patients with recurrent platinum‐sensitive ovarian cancer.

Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial

PURPOSE Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)–deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. METHODS This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control. RESULTS Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P &lt; .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1–positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents. CONCLUSION Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer.

Tisotumab vedotin in Japanese patients with recurrent or metastatic cervical cancer: results from the innovaTV 301/ENGOT-cx12/GOG-3057 trial

Tisotumab vedotin resulted in significantly longer overall survival compared with chemotherapy as second- or third-line therapy for recurrent or metastatic cervical cancer in the phase III, multi-national, open-label innovaTV 301/ENGOT-cx12/GOG-3057 trial. We report the results of a sub-group analysis of enrolled Japanese patients. Patients were randomized 1:1 to tisotumab vedotin or investigator-choice chemotherapy (topotecan [nogitecan hydrochloride], vinorelbine, gemcitabine, irinotecan, or pemetrexed). The primary end point was overall survival. Among 502 randomized patients, 101 were Japanese (tisotumab vedotin, n = 50; chemotherapy, n = 51). With 13.7 months of median follow-up in Japanese patients, median overall survival was 15.0 months (95% confidence interval [CI] 9.7 to not estimable) with tisotumab vedotin and 8.5 months (95% CI 6.8 to 10.6) with chemotherapy, representing a 55% lower risk of death with tisotumab vedotin than chemotherapy (hazard ratio 0.45, 95% CI 0.27 to 0.77). Median progression-free survival was 4.0 months (95% CI 3.0 to 4.4) with tisotumab vedotin and 2.0 months (95% CI 1.5 to 3.0) with chemotherapy (hazard ratio 0.63, 95% CI 0.42 to 0.95). The confirmed objective response rate was 24.0% (95% CI 13.1 to 38.2) with tisotumab vedotin and 2.0% (95% CI 0.0 to 10.4) with chemotherapy. All patients in the tisotumab vedotin and chemotherapy arms had ≥1 treatment-emergent adverse event; grade ≥3 events occurred in 42.9% and 66.0%, respectively. Six patients (12.2%) discontinued tisotumab vedotin due to treatment-emergent adverse events. Consistent with global findings, tisotumab vedotin resulted in clinical improvement compared with chemotherapy across all efficacy end points, and demonstrated a manageable adverse event profile in Japanese patients with recurrent or metastatic cervical cancer.

Atezolizumab Trial in Endometrial Cancer - AtTEnd

Atezolizumab is an engineered humanised monoclonal immunoglobulin G1 antibody that binds selectively to PD-L1 and prevents its interaction with PD-1 and B7-1. In May 2016 atezolizumab was approved by the FDA for patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following any platinum-containing chemotherapy, or within 12 months of receiving chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant); in October 2016 it was approved by the FDA for patients with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy, and have progressed on an appropriate FDA-approved targeted therapy if their tumor has EGFR or ALK gene abnormalities. Finally, in April 2017 atezolizumab was granted accelerated approval by FDA for the first-line treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin chemotherapy. Combinations of atezolizumab with chemotherapeutic agents and/or targeted therapies were studied in different solid tumors such as melanoma, NSCLC, renal cell carcinoma and colorectal carcinoma. From these studies the AE profile of atezolizumab combinations were consistent with that of the individual agents. Finally, preliminary results of a Phase Ia study of Atezolizumab (NCT01375842) monotherapy in relapsed endometrial cancer were reported as abstract at ASCO 2017. Fifteen patients were evaluated for safety and efficacy with a minimum follow-up of 11.2 months. No G4-5 related AEs occurred. Regarding efficacy ORR was 13% \[2/15\] by RECIST. Atezolizumab seemed to have a favorable safety profile, with durable clinical benefit in some patients. Further studies with atezolizumab are warranted given its promising results in advanced endometrial cancer and the limited efficacy of current treatment options.