PD-L1 Did Not Predict Immunotherapy Benefit in CC
A post-hoc analysis of the phase 3 trial demonstrated that the addition of atezolizumab to chemotherapy plus bevacizumab provided clinical benefit regardless of PD-L1 combined positive score (CPS) status. This was among the results of the trial that Kristina Lindemann, MD, head of the Gynecological Oncology Center at Oslo University Hospital, Norway, presented at the European Society for Medical Oncology Gynecological Cancers Congress 2025.
Current Treatment Landscape
The treatment landscape for recurrent or metastatic cervical cancer has evolved significantly in recent years, according to Lindemann. Since the publication of GOG-240, platinum-based chemotherapy with or without bevacizumab has served as the standard of care for chemotherapy-naive patients.
She noted, during her presentation, that the Keynote 826 study further established pembrolizumab plus chemotherapy and bevacizumab as a treatment option, but only for biomarker-positive patients with a CPS of at least 1.
The question that remains now is 'can we further improve the efficacy' of chemotherapy by adding immunotherapy in the biomarker-negative population, that is in those with a CPS of less than 1 or an unknown PD-L1 status?
BEATcc Trial Design and First Results
The BEATcc trial was an open-label, multicenter randomized phase 3 study in an all-comer population of 410 patients with recurrent or metastatic cervical cancer who had received no prior systemic anticancer therapy. Patients were randomized 1:1 to receive either atezolizumab plus bevacizumab and platinum-based chemotherapy or the control arm of bevacizumab and platinum-based chemotherapy alone.
The trial met its dual primary endpoints of progression-free survival (PFS) and interim overall survival (OS). Lindemann reported that the addition of atezolizumab to the backbone of chemotherapy and bevacizumab significantly increased both PFS and interim OS, with an increase in median PFS from 10.4 months to 13.7 months (hazard ratio [HR], 0.62; 95% CI, 0.49-0.78). Median OS was 32.1 and 22.8 months, respectively (HR, 0.68; 95% CI, 0.52-0.88).
Biomarker Analysis
The post hoc analysis presented by Lindemann examined treatment efficacy according to PD-L1 status in 313 patients (76% of the randomized population) who had available CPS scores. The analysis showed that the addition of atezolizumab to chemotherapy and bevacizumab provided benefit across all CPS subgroups.
In the CPS-negative group (CPS < 1), PFS improved from 10.2 months in the control group to 13.6 months with atezolizumab (HR, 0.48; 95% CI, 0.28-0.82). Similarly, in the CPS-positive group (CPS ≥ 1), the median PFS increased from 10.5 months to 16.6 months (HR, 0.54; 95% CI, 0.39-0.74). Interaction tests showed no predictive effect of CPS for PFS ( P = .73), PFS2 ( P = .53), or OS ( P = .12).
Commenting on these data, Lindemann emphasized that 'atezolizumab demonstrates efficacy in terms of providing a significant beneficial effect on PFS as well as interim OS, both in the intention-to-treat population, but also in the biomarker-evaluable population, and this efficacy was seen across all CPS cut-offs.'
Stéphanie Lheureux, of Princess Margaret Cancer Centre, Toronto, Ontario, who served as the external discussant, provided context regarding the interpretation of these biomarker analyses. She highlighted critical differences between the BEATcc and Keynote 826 trials in their approach to biomarker assessment.
'It's important to note that for both trials, the primary endpoint was a dual primary endpoint with both OS and PFS, which was powered for the trial design. They both used the same specific CPS core biomarker, but the way they analyzed the biomarker was very different in the two trials,' Lheureux noted.
She explained that, in Keynote 826, CPS score was prospectively assessed as a stratification factor and was well-balanced between groups, with CPS < 1 representing about 10% of the population. In contrast, the BEATcc biomarker analysis was conducted as a post hoc analysis, with 24% of patients lacking CPS scores and some imbalance between treatment groups.
'We need to be very careful when we look at subgroup analysis. The clinical trial design matters very much when we analyze the results,' Lheureux cautioned. 'If the subgroup analysis is not powered, it could just be hypothesis generating, and we need to be very careful of how we interpret this.'
Clinical Implications and Future Perspectives
The findings of BEATcc have already influenced clinical practice guidelines.
'The BEAT regimen is now listed as a preferred first-line regimen in these patients' in the updated National Comprehensive Cancer Network guidelines, reflecting the potential for broader application of atezolizumab regardless of biomarker status, Lindemann explained.
Looking ahead, Lheureux emphasized that more sophisticated approaches to personalized treatment selection using biomarkers are needed.
"We need to make sure biomarkers are context specific and appropriately validated with the right rigorous trials, and we need to assess the potential evolution of this biomarker with the tumor evolution and heterogeneity,' she said.
Lindemann said the final OS analysis from the BEATcc trial is expected in 2026, which may provide additional insights into the long-term benefits of the atezolizumab combination across different biomarker subgroups.
'In the BEATcc trial, PD-L1 status does not seem to be a robust biomarker guiding patient selection for immunotherapy in this setting.' The findings suggest that atezolizumab, in combination with bevacizumab and chemotherapy, 'represents an effective first-line treatment option for patients with recurrent [or] metastatic cervical cancer and should actually be offered irrespective of CPS,' she concluded.
Lindemann reports financial relationships with GSK, MSD, AstraZeneca, Karyopharm, Eisai, and Genmab.
Lheureux reports financial relationships with AstraZeneca, Repare Therapeutics, GSK, Schrodinger, Merck, Roche, Seagen, AbbVie, Zai Lab, Gilead, and Eisai.
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