A comprehensive post hoc analysis of the pivotal phase 3 BEATcc trial has revealed that adding atezolizumab to standard chemotherapy and bevacizumab delivers consistent clinical benefits in patients with untreated recurrent or metastatic cervical cancer, regardless of PD-L1 combined positive score (CPS). The findings, presented at the ESMO Gynaecological Cancers Congress 2025, challenge the predictive value of PD-L1 expression in this treatment paradigm and potentially expand treatment options for a broader patient population.
Consistent Efficacy Across PD-L1 Subgroups
The analysis, conducted with a median follow-up of 32.8 months, included 313 patients from the original 410-patient cohort, with approximately 70% having a PD-L1 CPS of ≥1. The results demonstrated that patients with PD-L1 CPS ≥1 experienced significant progression-free survival (PFS) benefit with atezolizumab (HR 0.54; 95% CI 0.39-0.74), achieving a median PFS of 16.6 months compared to 10.5 months without atezolizumab.
Notably, patients with PD-L1 CPS <1 showed a similar magnitude of PFS improvement (HR 0.48; 95% CI 0.28-0.82), with median PFS of 13.6 months versus 10.2 months in the control arm. The statistical evaluation for interaction between PD-L1 CPS status and PFS benefit yielded a P-value of 0.73, indicating no predictive effect of CPS for PFS outcomes.
Survival Benefits Extend Beyond Primary Endpoints
The consistent findings extended to secondary endpoints, including PFS2 (time from randomization to second progression or death). Median PFS2 values were 23.3 months for patients with CPS ≥1 and 24.3 months for those with CPS <1 in the atezolizumab combination arm, with an interaction P-value of 0.53.
Interim overall survival analysis revealed particularly striking results in the low PD-L1 expression group. Patients with CPS <1 showed a median OS of 37.3 months with atezolizumab versus 19.2 months without (HR 0.43; 95% CI 0.24-0.77). In the CPS ≥1 population, median OS was 33.2 months with atezolizumab compared to 26.5 months without (HR 0.73; 95% CI 0.51-1.06).
Addressing Unmet Medical Need
Professor Kristina Lindemann from Oslo University Hospital, the presenting study author, emphasized the clinical significance of these findings. "BEATcc confirms the clinical benefit of combined inhibition of immunosuppression and angiogenesis in recurrent or metastatic cervical cancer and shows that PD-L1 does not seem to be a robust biomarker guiding patient selection for immunotherapy in this population," she stated.
The results address a significant unmet need identified following the KEYNOTE-826 trial, which demonstrated the efficacy of pembrolizumab in combination with chemotherapy with or without bevacizumab specifically in patients with PD-L1 CPS ≥1. This left patients with CPS <1 or unknown PD-L1 status without clear immunotherapy options.
Clinical Practice Implications
Christian Marth, professor and head of the Department of Obstetrics and Gynecology at Innsbruck Medical University in Austria, commented on the trial's design significance, noting that BEATcc consistently included bevacizumab for all patients and demonstrated impressive PFS benefits across the board. "This is an important step forward and means that we could now consider immunotherapy in combination with bevacizumab regardless of PD-L1 status," he stated.
The atezolizumab combination is now among the preferred first-line regimens for patients with recurrent or metastatic cervical cancer in the latest National Comprehensive Cancer Network guidelines, according to Lindemann.
Safety Profile and Future Directions
The safety profile of the atezolizumab combination showed that grade 3 or worse adverse events occurred in 79% of patients in the experimental group compared with 75% in the standard group. While atezolizumab addition was associated with increased incidence of grade 1 to 2 diarrhea, arthralgia, pyrexia, and rash, these adverse events were generally manageable.
Looking ahead, Marth suggested potential advancements could involve bispecific immunotherapy and strategic combinations of immunotherapy with antibody-drug conjugates, such as tisotumab vedotin, which has demonstrated activity in later-line settings.
The BEATcc trial originally enrolled patients from October 2018 to August 2021, with participants receiving either 1200 mg of atezolizumab plus 15 mg/kg of bevacizumab and chemotherapy every 3 weeks, or bevacizumab and chemotherapy alone. Final overall survival results are expected in 2026, which will provide definitive long-term outcome data for this treatment approach.
