Ritu Salani

Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian Cancer: ASCO Guideline Update

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and 2 (online only) for more . PURPOSE To provide updated guidance regarding neoadjuvant chemotherapy (NACT) and primary cytoreductive surgery (PCS) among patients with stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer (epithelial ovarian cancer [EOC]). METHODS A multidisciplinary Expert Panel convened and updated the systematic review. RESULTS Sixty-one studies form the evidence base. RECOMMENDATIONS Patients with suspected stage III-IV EOC should be evaluated by a gynecologic oncologist, with cancer antigen 125, computed tomography of the abdomen and pelvis, and chest imaging included. All patients with EOC should be offered germline genetic and somatic testing at diagnosis. For patients with newly diagnosed advanced EOC who are fit for surgery and have a high likelihood of achieving complete cytoreduction, PCS is recommended. For patients fit for PCS but deemed unlikely to have complete cytoreduction, NACT is recommended. Patients with newly diagnosed advanced EOC and a high perioperative risk profile should receive NACT. Before NACT, patients should have histologic confirmation of invasive ovarian cancer. For NACT, a platinum-taxane doublet is recommended. Interval cytoreductive surgery (ICS) should be performed after ≤four cycles of NACT for patients with a response to chemotherapy or stable disease. For patients with stage III disease, good performance status, and adequate renal function treated with NACT, hyperthermic intraperitoneal chemotherapy may be offered during ICS. After ICS, chemotherapy should continue to complete a six-cycle treatment plan with the optional addition of bevacizumab. Patients with EOC should be offered US Food and Drug Administration–approved maintenance treatments. Patients with progressive disease on NACT should have diagnosis reconfirmed via tissue biopsy. Patients without previous comprehensive genetic or molecular profiling should be offered testing. Treatment options include alternative chemotherapy regimens, clinical trials, and/or initiation of end-of-life care. Additional information is available at www.asco.org/gynecologic-cancer-guidelines . This guideline has been endorsed by the Society of Gynecologic Oncology.

Real-world outcomes of first-line maintenance niraparib monotherapy in patients with epithelial ovarian cancer

To assess real-world progression-free survival (rwPFS) and time to next treatment (rwTTNT) among patients with epithelial ovarian cancer (EOC) who received first-line maintenance (1LM) niraparib monotherapy. In this US-nationwide, electronic health record-derived, deidentified database study, eligible patients with EOC initiated 1LM niraparib monotherapy (1 January 2017-1 December 2022) following first-line platinum-based chemotherapy. Median rwPFS and rwTTNT were estimated with Kaplan-Meier methodology overall and in a homologous recombination-deficient (HRd) subgroup (further stratified as Observed median rwPFS was 11.4 (95% CI, 10.1-12.7) months overall ( The real-world observed median rwPFS and rwTTNT were longer for patients with EOC who received 1LM niraparib monotherapy in the HRd subgroup (specifically for the

Preoperative predictors of endometrial cancer at time of hysterectomy for endometrial intraepithelial neoplasia or complex atypical hyperplasia

Endometrial intraepithelial neoplasia, also known as complex atypical hyperplasia, is a precancerous lesion of the endometrium associated with a 40% risk of concurrent endometrial cancer at the time of hysterectomy. Although a majority of endometrial cancers diagnosed at the time of hysterectomy for endometrial intraepithelial neoplasia are low risk and low stage, approximately 10% of patients ultimately diagnosed with endometrial cancers will have high-risk disease that would warrant lymph node assessment to guide adjuvant therapy decisions. Given these risks, some physicians choose to refer patients to a gynecologic oncologist for definitive management. Currently, few data exist regarding preoperative factors that can predict the presence of concurrent endometrial cancer in patients with endometrial intraepithelial neoplasia. Identification of these factors may assist in the preoperative triaging of patients to general gynecology or gynecologic oncology. To determine whether preoperative factors can predict the presence of concurrent endometrial cancer at the time of hysterectomy in patients with endometrial intraepithelial neoplasia; and to describe the ability of preoperative characteristics to predict which patients may be at a higher risk for lymph node involvement requiring lymph node assessment at the time of hysterectomy. We conducted a retrospective cohort study of women undergoing hysterectomy for pathologically confirmed endometrial intraepithelial neoplasia from January 2004 to December 2015. Patient demographics, imaging, pathology, and outcomes were recorded. The "Mayo criteria" were used to determine patients requiring lymphadenectomy. Unadjusted associations between covariates and progression to endometrial cancer were estimated by 2-sample t-tests for continuous covariates and by logistic regression for categorical covariates. A multivariable model for endometrial cancer at the time of hysterectomy was developed using logistic regression with 5-fold cross-validation. Of the 1055 charts reviewed, 169 patients were eligible and included. Of these patients, 87 (51.5%) had a final diagnosis of endometrial intraepithelial neoplasia/other benign disease, whereas 82 (48.5%) were ultimately diagnosed with endometrial cancer. No medical comorbidities were found to be strongly associated with concurrent endometrial cancer. Patients with endometrial cancer had a thicker average endometrial stripe compared to the patients with no endometrial cancer at the time of hysterectomy (15.7 mm; standard deviation, 9.5) versus 12.5 mm; standard deviation, 6.4; P = .01). An endometrial stripe of ≥2 cm was associated with 4.0 times the odds of concurrent endometrial cancer (95% confidence interval, 1.5-10.0), controlling for age. In all, 87% of endometrial cancer cases were stage T1a (Nx or N0). Approximately 44% of patients diagnosed with endometrial cancer and an endometrial stripe of ≥2 cm met the "Mayo criteria" for indicated lymphadenectomy compared to 22% of endometrial cancer patients with an endometrial stripe of <2 cm. Endometrial stripe thickness and age were the strongest predictors of concurrent endometrial cancer at time of hysterectomy for endometrial intraepithelial neoplasia. Referral to a gynecologic oncologist may be especially warranted in endometrial intraepithelial neoplasia patients with an endometrial stripe of ≥2 cm given the increased rate of concurrent cancer and potential need for lymph node assessment.

A non-comparative, randomized, phase II trial of atezolizumab or atezolizumab plus tiragolumab for programmed death-ligand 1-positive recurrent cervical cancer (SKYSCRAPER-04)

To evaluate tiragolumab (anti-TIGIT) and atezolizumab (anti-PD-L1) as second- or third-line therapy for PD-L1-positive persistent/recurrent cervical cancer. In the open-label, non-comparative, randomized phase II SKYSCRAPER-04 trial (NCT04300647), patients with PD-L1-positive (SP263 tumor area positivity ≥5%) recurrent/persistent cervical cancer after 1-2 chemotherapy lines (≥1 platinum-based) were randomized 3:1 to atezolizumab 1200 mg with/without tiragolumab 600 mg every 3 weeks until disease progression or unacceptable toxicity. Stratification factors were performance status, prior (chemo)radiotherapy, and disease status. The primary endpoint was independent review committee-assessed confirmed objective response rate per RECIST v1.1 in patients receiving tiragolumab plus atezolizumab. An objective response rate ≥21% (one-sample z-test p≤0.0245) was required for statistical significance versus a historical reference. Protocol-defined independent review committee-assessed objective response rates were 19.0% (95% CI 12.6 to 27.0) in 126 patients receiving tiragolumab plus atezolizumab (p=0.0787 vs historical reference) and 15.6% (95% CI 6.5 to 29.5) in 45 atezolizumab-treated patients. Response rates were higher in PD-L1 The objective response rate with the tiragolumab-plus-atezolizumab combination was numerically higher than the historical reference but did not reach statistical significance.

Exploratory evaluation of the somatic and immunologic landscape of primary and metastatic cervical cancer to better inform future clinical trial development.

To explore the somatic and immunologic landscape of cervical primary versus metastatic tumors for differential sensitivity of metastatic cervical sites and potential therapeutic implications. Patients with sequenced squamous cell cervical cancer were selected from the Tempus Database (2016-2023). The cohort included 136 unmatched samples (73 primary, 63 metastatic sites). Pathogenic somatic mutations and gene expression patterns of immune cells were evaluated for relative intratumor abundance. Immune cell percentages, tumor mutational burden, and tumor neoantigen burden (tumor mutational burden) were compared across tumor sites. χ The median cohort age was 52 years (interquartile range; 42-60). High tumor mutational burden (≥ 10 mut/Mb) was seen in 9.6% (9% primary, 0% lung, 17% liver, 17% lymph node, p = .7) of patients. High microsatellite instability (MSI) was noted in 1.5% (p = .7) of patients. PD-L1 status was positive in 78% (76% primary, 88% lung, 71% liver, and 80% lymph node, p = .8) of patients. Median tumor neoantigen burden was 1.71 (interquartile range; 0.98-3.20). Liver lesions had the lowest percentage of B cells (p = .001) and a higher percentage of macrophages (p = .053) compared with other sites. There was a trend toward lower percentages of CD4 cells (p = .053) and natural killer cells (p = .090) in lymph nodes compared with other sites. PIK3CA was the most common pathogenic somatic alteration but not statistically different across sites (q = 0.9). Molecular and immune profiling of primary and metastatic lesions indicated that liver lesions had a less immunogenic microenvironment. Further interrogation of the molecular landscape across paired samples is needed to better inform the development and use of novel therapies.

Mirvetuximab soravtansine in the ovarian cancer treatment landscape: influence of prior taxane exposure on outcomes.

To evaluate prescribing patterns, toxicities, and outcomes among patients receiving mirvetuximab for platinum-resistant ovarian cancer. This retrospective study included patients with platinum-resistant ovarian cancer with high folate receptor alpha expression treated with mirvetuximab at a single institution (2018-2023). Patients were categorized based on treatment immediately preceding mirvetuximab: the taxane group received taxane treatment; the non-taxane group received other therapy. An age-matched cohort of platinum-resistant patients not treated with mirvetuximab was included for survival comparison. Statistical analyses included descriptive statistics, Kaplan-Meier curves, log-rank tests, Wilcoxon rank-sum tests, and Cox models. Forty-one patients received mirvetuximab, with a median of 8 cycles (range; 1-47). Grade ≥3 adverse events included ocular (n = 6; 15%), hematologic (n = 1; 2%), neuropathy (n = 1; 2%), and pneumonitis (n = 1; 2%). Dose reductions and delays occurred in 26 (63%) and 21 (51%) patients, respectively. Mirvetuximab was discontinued in 40 patients (98%), most commonly due to disease progression (n = 35; 88%). Mirvetuximab-treated patients had longer median overall survival from diagnosis compared to the age-matched cohort without mirvetuximab exposure (83.12 vs 52.14 months; HR 0.34, 95% CI 0.18 to 0.64, p < .001). Among patients who received taxane therapy immediately before mirvetuximab (n = 9), average treatment duration was 5 months (9 cycles), with no grade ≥3 neuropathy. In those who received a non-taxane regimen immediately before mirvetuximab (n = 32), average treatment duration was 6 months (8 cycles), with 1 patient (3%) experiencing grade ≥3 neuropathy. Median progression-free survival was similar between groups (5.49 vs 6.28 months; HR 1.30, 95% CI 0.61 to 2.78, p = .50), but overall survival was shorter in the taxane group (11.28 vs 21.02 months; HR 2.47, 95% CI 1.01 to 6.04, p = .048). Real-world experience with mirvetuximab demonstrated a favorable safety profile and clinical benefit in platinum-resistant ovarian cancer. Taxane therapy immediately preceding mirvetuximab was associated with shorter overall survival but not increased neurotoxicity.

Real-world duration of first-line maintenance niraparib monotherapy in patients with epithelial ovarian cancer in the United States: the CHAR1ZMA study

The CHAR1ZMA study described real-world duration of first-line maintenance niraparib monotherapy among patients with epithelial ovarian cancer. This retrospective study used a US nationwide, electronic-health-record-derived, de-identified database. Eligible patients were aged ≥18 years with epithelial ovarian cancer who initiated first-line maintenance niraparib monotherapy (January 2017-December 2022 [inclusive]) following first-line platinum-based chemotherapy. Niraparib monotherapy duration was measured as the time to treatment discontinuation, estimated using Kaplan-Meier methodology, overall and stratified by treatment duration (early discontinuers [≤90 days]; non-early discontinuers [>90 days or did not discontinue]). Analyses were repeated in a sub-group of patients with homologous recombination-deficient tumors. Toxicity was the most common reason for niraparib discontinuation among early discontinuers (67.7%) and was less frequent among non-early discontinuers (18.1%). Dose modifications were less frequent among early discontinuers (29.8%) than non-early discontinuers (53.6%). Disease progression was the most common reason for niraparib discontinuation among non-early discontinuers (74.8%) and was less frequent among early discontinuers (30.4%). The observed median treatment duration was 7.2 months (95% CI 6.0 to 8.1) overall (N = 560) and was 4.5 months longer among non-early discontinuers (11.7 months [95% CI 9.8 to 14.7]; n = 399). In the homologous recombination-deficient sub-group (n = 144), the observed median treatment duration was 11.6 months (95% CI 7.8. to 16.1) and was 5.1 months longer among non-early discontinuers (16.7 months [95% CI 12.0 to 22.8]; n = 114). In this real-world study of patients with epithelial ovarian cancer receiving first-line maintenance niraparib monotherapy, drug toxicity was the most common reason for treatment discontinuation in early discontinuers. Effective and early clinical management of drug toxicity may help mitigate these adverse events, allowing patients to remain on niraparib maintenance treatment longer and experience the potential full therapeutic benefit.

A Study of Tiragolumab Plus Atezolizumab and Atezolizumab Monotherapy in Participants With Metastatic and/or Recurrent PD-L1-Positive Cervical Cancer

The purpose of this study is to evaluate the efficacy and safety of tiragolumab in combination with atezolizumab and atezolizumab monotherapy in patients with programmed death-ligand 1 (PD-L1)-positive cervical cancer (metastatic and/or recurrent).