Adding Atezolizumab Improves Survival in Advanced Cervical Cancer

— Trial confirms the role of first-line checkpoint inhibition in metastatic or recurrent disease

by
Leah Lawrence, Contributing Writer, MedPage Today
November 3, 2023

First-line treatment with the anti-PD-L1 inhibitor atezolizumab (Tecentriq) combined with bevacizumab (Avastin) and platinum-based chemotherapy significantly improved survival in patients with metastatic or recurrent cervical cancer, according to results of the phase III BEATcc trial.

The median progression-free survival (PFS) was 13.7 months with added atezolizumab compared with 10.4 months with the standard bevacizumab plus chemotherapy (HR 0.62, 95% CI 0.49-0.78, P<0.0001), reported Ana Oaknin, MD, of Vall d'Hebron University Hospital in Barcelona, during a European Society for Medical Oncology (ESMO) Virtual Plenary.

An interim analysis of overall survival (OS) also showed a statistically significant and clinically meaningful benefit with the addition of atezolizumab (median OS 32.1 vs 22.8 months; HR 0.68, 95% CI 0.52-0.88, P=0.0046).

Oaknin did not yet have outcome data based on PD-L1 expression. However, the PFS and OS benefits were seen across all protocol-defined subgroups, including patients with squamous cell carcinoma — a histology with high PD-L1 positivity — and adenocarcinoma — a histology with lower rates of PD-L1 positivity, she pointed out.

Oaknin noted that the control arm was an existing standard of care, thus building on this standard, rather than comparing the investigational arm with chemotherapy alone.

“These results indicate that atezolizumab in combination with bevacizumab added to platinum-based chemotherapy should be considered a new first-line therapy option for patients with metastatic, persistent, or recurrent cervical cancer,” she said.

In his discussion of the study, Bradley J. Monk, MD, of the University of Arizona College of Medicine in Phoenix, said that these positive results are “more good news for patients,” and that there are now two trials reporting the efficacy of checkpoint inhibition in this setting.

Monk referred to the KEYNOTE-826 trial, which compared the anti-PD-1 inhibitor pembrolizumab (Keytruda) plus chemotherapy versus placebo plus chemotherapy — with bevacizumab given at the investigator’s discretion. Patients with PD-L1-positive tumors had a median OS of 28.6 months compared with 16.5 months for bevacizumab plus chemotherapy, with similar results among all-comers.

Monk said this is relevant to BEATcc because it reflects real-world situations in which bevacizumab cannot always safely be given, for medical or non-medical reasons. KEYNOTE-826 showed that whether or not a patient received bevacizumab, the addition of the checkpoint inhibitor improved OS.

Discussing the two trials, Monk said, “I have two daughters and I like them both the same. What is important is that I give them both attention. What is important here is to give immunotherapy.”

The results of BEATcc not only confirm the results of KEYNOTE-826, Monk concluded, but also confirm the importance of bevacizumab in the first-line treatment of metastatic, persistent, or recurrent cervical cancer.

The open-label BEATcc trial enrolled 410 patients regardless of PD-L1 expression and randomly assigned them to first-line chemotherapy plus bevacizumab with (n=206) or without atezolizumab (n=204).

Median age in the atezolizumab group was 51, and 54% were white. Median age in the standard-care group was 52.5, and 55% were white. A majority of patients in both groups had an Eastern Cooperative Oncology Group performance status score of 0.

The data on the dual primary endpoints was supported by meaningful improvements in several secondary endpoints as well. Patients who received added atezolizumab had an overall response rate (ORR) of 84% and a complete response (CR) rate of 32% compared with an ORR of 72% and a CR rate of 20% for those who received bevacizumab plus chemotherapy alone.

There was also a significant improvement in duration of response with the addition of atezolizumab compared with standard of care (median 13.6 vs 8.6 months; HR 0.60, 95% CI 0.46-0.78), and a consistent benefit in time to first subsequent therapy (HR 0.60, 95% CI 0.47-0.76) and PFS2 (HR 0.61, 95% CI 0.48-0.79).

The benefit from combining atezolizumab with bevacizumab and chemotherapy was achieved without an increase in toxicity, Oaknin said, with no new safety signals observed.