Frederik Marmé, MD, PhD, Heidelberg University, Mannheim, Germany, discusses results from the phase 3 AGO-OVAR 2.29/ENGOT-ov34 study, evaluating the efficacy of atezolizumab plus bevacizumab and chemotherapy (paclitaxel or pegylated liposomal doxorubicin) among patients with recurrent ovarian cancer. In this study, the addition of atezolizumab was not associated with a benefit in survival outcomes.

As Dr Marmé summarized, “What we've…learned is that all the potential combination with bevacizumab as well as chemo and with PARP inhibitors do not lead to a clinically meaningful benefit of immunotherapy. However, in each of these trials we see a minority of patients benefiting significantly in terms of OS, but we've not been able to identify these patients.”

Transcript:

Hello, my name is Frederik Marmé, I'm a gynecologic oncologist at the medical faculty Mannheim of the University of Heidelberg. I'm here at ASCO 2024 and I've presented our data of the AGO 2.29/ENGOT-ov34 study today.

Just to give you an idea of what this study was about, it's a study investigating immunotherapy (IO) in recurrent platinum-resistant ovarian cancer. We specifically investigated the combination of IO, atezolizumab in that case, with chemotherapy and bevacizumab.

The trial enrolled 574 patients with up to 3 prior lines of therapy. They were allowed to have a prior therapy with bevacizumab and were stratified by prior lines of therapy, use of the chemotherapeutic agent in this study, paclitaxel or pegylated liposomal doxorubicin, the chemotherapy backbone, and also stratified by prior use of bevacizumab, and PD-L1 status. They were randomized 1-to-1 to receive either atezolizumab as a PD-L1 inhibitor or placebo in combination with chemotherapy plus bevacizumab. The primary end points of the study were overall survival (OS) as well as progression free survival (PFS) with a split alpha for OS of .045 and .005 for PFS. There were some secondary end points reported as well, duration of response, overall response rate, safety, and tolerability.

To conclude, the study didn't meet its primary end point. At a maturity of 88% of events, there was no benefit in terms of progression-free survival by the addition of atezolizumab to chemotherapy and bevacizumab and similarly looking at the overall survival, that was not significantly improved with a median overall survival of 14.2 versus 13 months by the addition of atezolizumab to chemotherapy and bevacizumab.

We observed some signals of efficacy looking at the response and specifically at the duration of response. Response rates were similar between both treatment arms but there was a numerically longer duration of response in the atezolizumab arm with more than 2 months difference. If you look at a landmark analysis of overall survival at 24 months, which is shorter than the median follow-up time, there's an 8% difference in overall survival favoring atezolizumab and the Kaplan-Meier curves stay separate until the end of observation. Obviously, that came at the cost of increased toxicities, we had more immune-related adverse events (AEs) in the atezolizumab arm, that was 12% versus 6% in the placebo arm, but they were largely manageable. The discontinuation rate due to AEs for atezolizumab was 16% versus 14% in the placebo arm.

To conclude what we've seen here in a combination with bevacizumab, immunotherapy (atezolizumab), and chemotherapy really is in line with many other trials that have been conducted investigating immunotherapy in ovarian cancer from the first-line over the platinum-sensitive setting and in the platinum-resistant setting. What we've seen and learned is that all the potential combination with bevacizumab as well as chemotherapy and with PARP inhibitors do not lead to a clinically meaningful benefit of immunotherapy. However, in each of these trials we see a minority of patients benefiting significantly in terms of OS, but we've not been able to identify these patients. Also in our trial, PD-L1 status is not predictive for benefit of atezolizumab.

Source:

Marmé F, Harter P, Redondo A, et al. Atezolizumab versus placebo in combination with bevacizumab and non-platinum-based chemotherapy in recurrent ovarian cancer: Final overall and progression-free survival results from the AGO-OVAR 2.29/ENGOT-ov34 study. Presented at the 2024 ASCO Annual Meeting. May 31-June 4, 2024; Chicago, IL. Abstract #LBA5501