Atezolizumab Efficacy in Cervical Cancer Consistent Irrespective of PD-L1
Microscopic, photorealistic image of cervical cancer cells - Generated with Adobe Firefly
A post hoc analysis of the pivotal phase 3 BEATcc trial (NCT03556839) has revealed that the clinical benefits of adding atezolizumab (Tecentriq) to standard chemotherapy and bevacizumab (Avastin) in patients with untreated recurrent or metastatic cervical cancer are consistent, irrespective of PD-L1 combined positive score (CPS). These findings, presented at the ESMO Gynaecological Cancers Congress 2025, suggest that PD-L1 expression may not serve as a predictive biomarker for atezolizumab efficacy in this specific treatment paradigm, potentially broadening the eligible patient population for this immunotherapeutic combination.1
The BEATcc trial previously established that the inclusion of atezolizumab significantly improved both progression-free survival (PFS) and overall survival (OS) when added to a backbone of cisplatin or carboplatin, paclitaxel, and bevacizumab for patients with metastatic, persistent, or recurrent cervical cancer. The original trial, an investigator-initiated, randomized, open-label, phase 3 study, enrolled 410 patients from October 2018 to August 2021.
The initial results demonstrated a median PFS of 13.7 months (95% CI, 12.3-16.6) in the atezolizumab arm compared with 10.4 months (95% CI, 9.7-11.7) in the standard therapy arm (HR, 0.62; 95% CI, 0.49-0.78; P <.0001). An interim OS analysis also showed a substantial benefit, with a median OS of 32.1 months (95% CI, 25.3-36.8) vs 22.8 months (95% CI, 20.3-28.0), respectively (HR, 0.68; 95% CI 0.52-0.88; P =.0046). These initial outcomes positioned the atezolizumab combination as a new first-line therapy option.2
The recently presented post hoc analysis aimed to elucidate whether PD-L1 expression, as measured by CPS, could predict the magnitude of PFS benefit.1 The analysis was conducted with a median follow-up of 32.8 months and included 313 patients, approximately 70% of whom had a PD-L1 CPS of ≥1. The results indicated that patients with a PD-L1 CPS ≥1 experienced a significant PFS benefit with atezolizumab (HR 0.54; 95% CI 0.39-0.74). Notably, patients with a PD-L1 CPS <1 also demonstrated a similar magnitude of PFS improvement (HR 0.48; 95% CI 0.28-0.82). The statistical evaluation for interaction between PD-L1 CPS status and PFS benefit yielded a P-value of 0.73, signifying no predictive effect of CPS for PFS in this population receiving the atezolizumab, chemotherapy, and bevacizumab regimen.
These consistent findings extended to PFS2, defined as the 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, further reinforcing the nonpredictive nature of PD-L1 CPS in this context.
Interim analysis of OS similarly showed median values of 33.2 months for patients with CPS ≥1 and 37.3 months for those with CPS <1, with an interaction P-value of 0.12, although final OS results are still pending.
Christian Marth, MD, PhD, a professor in the head of the Department of Obstetrics and Gynecology at Innsbruck Medical University in Austria, commented on these findings, noting that the BEATcc trial corroborates the survival advantages observed in the KEYNOTE-826 trial (NCT03635567), which investigated pembrolizumab (Keytruda) in combination with chemotherapy with or without bevacizumab, albeit specifically in patients with a PD-L1 CPS ≥1. Prof Marth emphasized the significance of the BEATcc trial's design, which consistently included bevacizumab for all patients and the demonstration of 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 apparent immunogenicity of cervical cancer continues to drive the exploration of immunotherapy in earlier disease stages. However, Marth acknowledged the emerging clinical challenge that some patients in the metastatic setting may have already received immunotherapy earlier in their disease course. This necessitates further research to ascertain the feasibility and efficacy of readministering immunotherapy upon disease progression.
Looking ahead, Marth suggested that advancements could involve "bispecific immunotherapy" as a potential step up, as well as the strategic combination of immunotherapy with antibody-drug conjugates, such as tisotumab vedotin. (Tivdak), which has demonstrated activity in later-line settings.3 Such synergistic approaches hold promise for continued progress in the management of recurrent and metastatic cervical cancer.
The safety profile of the atezolizumab combination in the main BEATcc trial indicated that grade 3 or worse adverse events (AEs) occurred in 79% of patients in the experimental group compared with 75% in the standard group.1 While the addition of atezolizumab was associated with increased incidence of grade 1 to 2 diarrhea, arthralgia, pyrexia, and rash, these AEs were generally manageable.
Continued follow-up for final OS data and further translational research will be crucial to fully understand the long-term impact and refine treatment strategies in this patient population.
