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by Dr. C.H. Weaver M.D. 9/2022

Combination strategies of PD-1/PD-L1 inhibition with anti-angiogenic therapy have the potential for improved anti-cancer activity and represent a potential therapeutic opportunity for the treatment of advanced ovarian cancer.

In order to evaluate this approach doctors at Dana Farber Cancer Institute in Boston reported the results of a small single-arm clinical trial of 38 patients with relapsed epithelial ovarian cancer to assess the effectiveness of the checkpoint inhibitor Opdivo (nivolumab) plus Avastin (bevacizumab) therapy in recurrent ovarian cancer.

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Patients were eligible for inclusion in the trial if they had been given 1 to 3 previous lines of therapy and had disease recurrence within 12 months of their last platinum-based therapy. Of these patients, 18 had platinum-resistant disease and 20 had platinum-sensitive disease.

Overall the combination therapy with Opdivo-Avastin was generally well tolerated and led to response rates of 40% and 17% in patients with platinum-sensitive and platinum-resistant disease. The average duration of survival without ovarian cancer progression was 8.1 months.

The checkpoint inhibitor Avastin combination appeared to represent another treatment option for patients with relapsed ovarian cancer.

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Larger Studies Fail to Confirm Benefit

The ATALANTE clinical trial evaluated the addition of the checkpoint inhibitor Tecentriq (atezolizumab) to platinum-based chemotherapy plus bevacizumab for platinum-sensitive ovarian cancer and failed to show significant benefit. 

The ATALANTE trial is the first phase 3 trial to evaluate the addition of Tecentiriq to standard therapy in patients with recurrent, platinum-sensitive ovarian cancer. A total of 614 patients were treated with the investigator’s choice of platinum-based chemotherapy regimen and Avastin with or without Tecentriq and directly compared between October 2016 and September 2019. Patients were stratified by platinum-free survival, PD-L1 status, and type of chemotherapy.

With a median follow-up was 36 months the median survival duration without cancer progression was 13.5 months for Tecentriq compared to 11.2 months for placebo.  In the PD-L1-positive population it was 15.2 months compared to 13.1 months with placebo.2

Median overall survival was increased from 31 to 35 months with the addition of Tecentriq. The encouraging survival data warrant further analyses with longer follow-up.

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Reference:

  1. JAMA Oncol. 2019 Oct 10. Epub ahead of print.
  2. Kurtz JE, Pujade-Lauraine E, Oaknin A, et al. Phase III ATALANTE/ov29 trial: Atezolizumab (Atz) versus placebo with platinum-based chemotherapy (Cx) plus bevacizumab (bev) in patients (pts) with platinum-sensitive relapse (PSR) of epithelial ovarian cancer (OC). Presented at: ESMO Congress; September 9-13, 2022. Paris, France and virtual. Abstract LBA30.