Findings from a real-world study suggest that first-line quadruplet therapy with bevacizumab (Avastin) plus standard platinum-based chemotherapy and pembrolizumab (Keytruda) may improve clinical outcomes and serve as an optimal initial treatment for patients with advanced cervical cancer who do not display any contraindications for antiangiogenetic agents, according to Alberto Farolfi, MD, PhD.
Results presented during the 2025 ESMO Gynecological Cancers Congress showed that the addition of bevacizumab to carboplatin, paclitaxel, and pembrolizumab significantly improved clinical outcomes for patients with cervical cancer without negatively affecting the risk of serious toxicities. Among the 345 matched pairs of patients with advanced cervical cancer, the median overall survival [OS] was not reached vs 19.3 months for those who received the carboplatin-based regimen with or without bevaciuzumab, respectively (HR 0.62, 95% CI 0.47-0.82, P = 0.001); no differences in the incidence of fistula, bowel perforation, or pulmonary embolism were reported. Moreover, data suggested that adding bevacizumab to a cisplatin-based triplet may confer benefit. (HR, 0.48; 95% CI 0.31-0.72; P < 0.001).
“These data suggest that every time it is possible and not contraindicated, we should add bevacizumab to treatment with pembrolizumab [and platinum-based chemotherapy] for this [patient population]. The type of platinum we use is not as important,” Farolfi, a medical oncologist at Romagnolo Scientific Institute for the Study and Treatment of Tumors, in Meldola, Italy, stated in an interview with OncLive®.
In addition to expanding on key findings from this global network analysis, Farolfi also discussed the role of bevacizumab in advanced cervical cancer, noted potential study limitations due to missing biological and histological data, and outlined future research being planned to explore how prior chemoradiotherapy and histological subtypes affect outcomes with the quadruplet.
OncLive: What prior data from this global network analysis have been reported, and how did they inform the current investigation of outcomes with bevacizumab according to platinum chemotherapy regimen?
Farolfi: We presented results from our global network analysis on cervical cancer. The question we aimed to answer was: what is the best first-line treatment for patients with advanced disease? In the seminal trial of pembrolizumab, the choice of companion treatment—whether cisplatin or carboplatin, and whether to include bevacizumab—was [left to the discretion] of the treating physician. Based on that trial, we saw that pembrolizumab is effective in this patient population, but the question [remained] whether the choice of carboplatin or cisplatin could influence response, and whether the addition of bevacizumab to pembrolizumab could further improve outcomes.
Based on this rationale, we sought to extract patient data from a global collaborative network [that anonymizes] medical records from more than 150 hospitals. We tried to group patients by treatment: those who received cisplatin-based chemotherapy plus pembrolizumab, those who received carboplatin-based chemotherapy plus pembrolizumab, and then we compared outcomes in patients treated with or without bevacizumab.
At the 2025 ASCO Annual Meeting, we presented the data stratified by platinum agent and found that the type of platinum [chemotherapy] did not influence patient outcomes.
What efficacy and safety results were reported from this analysis of benefit with bevacizumab according to the platinum-based regimen administered?
At this year’s ESMO Gynecologic Cancers Congress, we focused on evaluating the additive value of bevacizumab, analyzing subgroups by type of platinum [chemotherapy]. We observed that the addition of bevacizumab improved outcomes in these patients. Specifically, the bevacizumab plus pembrolizumab–based treatment resulted in improved OS, with median OS approaching 1.5 years in the bevacizumab-treated group.
Interestingly, we did not observe any increase in adverse effects [AEs] with the addition of bevacizumab. Initially, we had concerns [about this], since we know it can cause rare but serious complications such as fistula formation, bowel perforation, or pulmonary embolism. Given the severity of these AEs, we also analyzed their incidence in the study population. We found no significant difference between patients treated with bevacizumab and those who were not.
[Additionally], patients who received bevacizumab actually [experienced] a reduced incidence of pulmonary embolism. This may seem unexpected at first, but it raises the hypothesis that bevacizumab could enhance the overall efficacy of treatment. This improved efficacy might in turn reduce the tumor-driven risk of thrombosis, which could explain the observed decrease in pulmonary embolism events.
What are some potential limitations or considerations when interpreting these data? How do these inspire potential next steps for investigation?
We [also acknowledge] a major limitation of our study: we only had access to the patients’ medical records. Although we know that patients could receive pembrolizumab only if they had a positive combined positive score, we did not have access to the biological data. Unfortunately, we also lacked histological data, so we were unable to assess whether outcomes differed based on histologic subtype, such as squamous cell carcinoma vs adenocarcinoma.
Another potential limitation to be underlined is that there could be selection bias, because when a clinician chooses to treat patients with the combination, they may [be in] better shape than the others. [The resulting favorable outcomes] could be [influenced by] that. [However], given the AE profile that we saw, our recommendation that patients be treated with all 4 drugs if possible, and as the best combination, remains.
[Accordingly,] a planned area of [future] analysis is to evaluate whether patients who were previously treated with combined chemotherapy and radiotherapy for locally advanced cervical cancer have different outcomes based on that prior treatment.
Overall, we hope to [publish these data in a] paper very soon, because they are very interesting and could be useful for the global community.
Reference
Farolfi A, Casadei C, Paoletti E, et al. Real-world evidence from a global network: The role of bevacizumab in advanced cervical cancer (aCC) patients treated with pembrolizumab and chemotherapy. Ann Oncol. 2023;10(suppl 5):105151. doi:10.1016/iotech/iotech100589