Phase II study of atezolizumab in combination with bevacizumab in patients with advanced cervical cancer

Abstract

BackgroundThere are limited treatment options for patients with metastatic or recurrent cervical cancer. Platinum-based chemotherapy plus the anti-vascular endothelial growth factor antibody bevacizumab remains the mainstay of advanced treatment. Pembrolizumab is Food and Drug Agency approved for programmed death ligand 1 (PD-L1) positive cervical cancer with a modest response rate. This is the first study to report the efficacy and safety of the PD-L1 antibody atezolizumab in combination with bevacizumab in advanced cervical cancer.MethodsWe report the results from a phase II, open-label, multicenter study (NCT02921269). Patients with advanced cervical cancer were treated with bevacizumab 15 mg/kg intravenous every 3 weeks and atezolizumab 1200 mg intravenous every 3 weeks. The primary objective was to measure the objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.ResultsIn the total evaluable population (n=10), zero patients achieved an objective response as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) V.1.1, resulting in a confirmed ORR of 0%. Of note, there were two patients who achieved an unconfirmed PR. The DCR by RECIST V.1.1 was 60% (0% complete response, 0% partial response, 60% stable disease). Median PFS was 2.9 months (95% CI, 1.8 to 6) and median OS was 8.9 months (95% CI, 3.4 to 21.9). Safety results were generally consistent with the known safety profile of both drugs, notably with two high-grade neurologic events.ConclusionsThe combination of bevacizumab and atezolizumab did not meet the predefined efficacy endpoint, as addition of bevacizumab to PD-L1 blockade did not appear to enhance the ORR in cervical cancer.

The potential oncogenic and MLN4924-resistant effects of CSN5 on cervical cancer cells

“…Approximately 20% of patients may recur despite the combined surgery, chemotherapy and radiotherapy [7]. At present, the combination of platinum, paclitaxel and bevacizumab is suggested to be the first choice of metastatic cervical cancer [8][9][10], but the prognosis remains poor in general [11][12][13][14]. It is a pressing need to discover potential therapeutic and diagnostic biomarkers to improve survival in women with cervical cancers.…”

Immunotherapy and Its Development for Gynecological (Ovarian, Endometrial and Cervical) Tumors: From Immune Checkpoint Inhibitors to Chimeric Antigen Receptor (CAR)-T Cell Therapy

“…However, another trial assessing nivolumab as subsequent-line therapy in previously treated CC patients reported poor results (only 4% ORR with 40% DCR) [54]. Similar results were obtained in a phase II trial testing the combination of anti-PD-L1 atezolizumab and anti-VEGF bevacizumab as subsequent-line therapy in 10 previously-treated CC patients (no responses and 50% DCR) [55].…”

Expanding Our Impact in Cervical Cancer Treatment: Novel Immunotherapies, Radiation Innovations, and Consideration of Rare Histologies

“…A separate cohort of the KEYNOTE-158 study focusing on patients with tumors exhibiting high tumor mutational burden, defined as 10 or more mutations per megabase, has led to U.S. Food and Drug Administration approval of pembrolizumab for patients with a tumor mutational burden of 10 or more irrespective of cancer type, including cervical cancer. 23 addition of bevacizumab to the PD-L1 blockade with atezolizumab in patients pretreated wtih bevacizumab did not appear to increase the response rate in an ETCTN-sponsored phase II study, prompting the study discontinuation after accrual of 10 patients to the first stage, 24 although interest still remains in this combination in an earlier line of therapy and with a survival end point. The number of additional agents targeting PD-1 and PD-L1 are currently being explored across a number of studies in recurrent/metastatic cervical cancer, both alone and in combination with frontline chemotherapy and bevacizumab (NCT03257267, NCT03830866, NCT03635567), or antibodies targeting other checkpoints such as CTLA-4 and TIGIT (NCT03894215, NCT04300647).…”