Patients with Newly Diagnosed Stage III or IV Ovarian Cancer and Atezolizumab

2020 Year in Review - Ovarian Cancer

Due to a variety of factors, first-line therapy with atezolizumab failed to demonstrate significant activity in patients with newly diagnosed stage III or stage IV ovarian cancer.

Atezolizumab is a monoclonal antibody that targets PD-L1. The IMagyn050A trial was a phase 3, multicenter, double-blind, 2-arm, randomized study examining the safety and efficacy of atezolizumab compared with placebo administered in combination with paclitaxel, carboplatin, and bevacizumab. Patients in the study were those with newly diagnosed stage III or IV ovarian, fallopian tube, or primary peritoneal cancer who underwent either primary cytoreductive surgery with gross residual disease or neoadjuvant chemotherapy and interval surgery (this patient subgroup was capped at 25% of the total study population). Of the total patient population, >75% had high-grade serous ovarian cancer.

Patients were randomized to either atezolizumab 1200 mg every 3 weeks (N = 650) or placebo for 22 cycles (N = 651) combined with paclitaxel (175 mg/m2) plus carboplatin (at AUC 6; cycles 1-6) and bevacizumab (15 mg/kg for cycles 2-22; bevacizumab was excluded in perioperative cycles). Stratification factors were stage III versus stage IV cancer and European Cooperative Oncology Group performance status of 0 versus 1 or 2. Patients were not stratified by homologous recombination deficiency (HRD) or BRCA status. The primary end points were progression-free survival (PFS) assessed per Response Evaluation Criteria in Solid Tumors and overall survival (OS) in both the intent-to-treat (ITT) and the PD-L1–positive populations.

The primary end point of improvement of PFS in the ITT population was not met (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.79-1.07); median PFS rates were 19.5 months and 18.4 months in the atezolizumab and placebo arms, respectively. In the subgroup of patients with PD-L1–positive tumors, PFS was also not significant (HR, 0.80; 95% CI, 0.65-0.99); median PFS rates were 20.8 months and 18.5 months in patients receiving atezolizumab (N = 391) and those in the placebo arm (N = 393), respectively. A subgroup analysis of PFS by baseline characteristic showed a trend toward improvement with treatment with atezolizumab in patients with stage III disease. Based on an interim analysis, OS showed that treatment with atezolizumab did not accord significant benefit in the ITT population (HR, 0.96; 95% CI, 0.74-1.26) or the PD-L1–positive subgroup (HR, 0.98; 95% CI, 0.68-1.41). However, an exploratory analysis for PFS in the subgroup of patients whose tumors had PD-L1 IC ≥5% (defined as the area of PD-L1 stained tumor-infiltrating immune cells as a percentage of the total tumor area) showed a trend favoring treatment with atezolizumab (HR, 0.64; 95% CI, 0.43-0.96). In this subgroup, median PFS rates were 20.2 months and not reached in the placebo and atezolizumab arms, respectively.

In patients with ovarian cancer, the incidence of treatment-emergent adverse events (AEs) was consistent with that of previous data regarding treatment with atezolizumab. The rate of treatment discontinuation because of AEs was comparable between the study arms; 22% of patients receiving placebo discontinued because of AEs and 26% of patients received atezolizumab doing so. Febrile neutropenia occurred in 8.4% and 3.7% of patients receiving atezolizumab and in the placebo group, respectively. Grade 3 or 4 AEs occurred in 67% and 75% of patients in the placebo and atezolizumab arms, respectively.

Authors concluded that as first-line therapy, atezolizumab failed to show significant activity in patients with newly diagnosed stage III or stage IV ovarian cancer. This may be attributable to study-related factors, including lack of stratification for HRD/BRCA, timing of PFS assessment, use of PFS as one of the primary study end points, and diagnostic performance limitations of the PD-L1 test. Exploratory biomarker subgroup analyses are ongoing.

Source: Moore KN, et al. Ann Oncol. 2020;31(4_suppl). Abstract LBA31.

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