Angiolo Gadducci

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.

Management of ovarian cancer: guidelines of the Italian Medical Oncology Association (AIOM)

Introduction: Ovarian cancer is the most lethal gynecologic malignancy. Over 5200 new cases of this tumor are diagnosed yearly in Italy, resulting in more than 3600 deaths. In terms of molecular biology, five different ovarian cancer subtypes should be distinguished. Method: This article summarizes the evidence-based guidelines that the Italian Medical Oncology Association (AIOM) has developed with a multidisciplinary panel of experts, including pathologists, gynecologic oncologists, medical oncologists, and radiotherapists, with the support of methodologists, to help clinicians involved in the management of patients with ovarian cancer in their daily clinical practice. Results: The most relevant randomized clinical trials regarding surgery, chemotherapy, and molecularly targeted agents (bevacizumab and PARP inhibitors) in early, advanced, and recurrent disease have been critically analyzed. The levels of evidence and strength of recommendation have been reported for any issue. Conclusion: Women with a clinical suspicion of ovarian cancer should be centralized in referral centers. The BRCA test should be requested for all women with nonmucinous and nonborderline tumors, regardless of age and family history. BRCA testing could be preferentially performed on neoplastic tissue. In the presence of a positive tumor test, a genetic test should always be performed on a blood sample to differentiate between germline mutations, which require counseling and genetic testing of family members, and somatic mutations.

MRI-based radiomics: promise for locally advanced cervical cancer treated with a tailored integrated therapeutic approach

Objective: To assess prognostic factors by analyzing clinical and radiomic data of patients with locally advanced cervical cancer (LACC) treated with definitive concurrent cisplatin-based chemoradiotherapy (CCRT) using magnetic resonance imaging (MRI). Methods: We analyzed radiomic features from MRI in 60 women with FIGO (International Federation of Gynecology and Obstetrics) stage IB2–IVA cervical cancer who underwent definitive CCRT 45–50.4 Gy (in 25–28 fractions). Thirty-nine (65.0%) received EBRT sequential boost (4–20 Gy) on primary tumor site and 56 (93.3%) received high-dose-rate brachytherapy boost (6–28 Gy) (daily fractions of 5–7 Gy). Moreover, 71.7% of patients received dose-dense neoadjuvant chemotherapy for 6 cycles. The gross tumor volume was defined on T2-weighted sequences and 29 features were extracted from each MRI performed before and after CCRT, using dedicated software, and their prognostic value was correlated with clinical information. Results: In univariate analysis, age ⩾60 years and FIGO stage IB2–IIB had significantly better progression-free survival (PFS) ( p = 0.022 and p = 0.009, respectively). There was a trend for significance for worse overall survival (OS) in patients with positive nodes ( p = 0.062). In multivariate analysis, only age ⩾60 years and FIGO stage IB2–IIB reached significantly better PFS ( p = 0.020 and p = 0.053, respectively). In radiomic dataset, in multivariate analysis, pregray level p75 was significantly associated with PFS ( p = 0.047), pre-D3D value with OS ( p = 0.049), and preinformation measure of correlation value with local control ( p = 0.031). Conclusion: The combination of clinical and radiomics features can provide information to predict behavior and prognosis of LACC and to make more accurate treatment decisions.

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.