Prof Christine Gennigens, a medical oncologist at CHU de Liège, and Prof Els Van Nieuwenhuysen, a gynaeco-oncologist at UZ Leuven, recently discussed the results of the ENGOT-cx11/GOG-3047/KEYNOTE-A18 trial, which investigated the efficacy and safety of pembrolizumab in combination with concurrent chemoradiotherapy for locally advanced cervical cancer.
The study involved patients with newly diagnosed, previously untreated, high-risk locally advanced cervical cancer, falling within the FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA. The patients were randomly assigned to one of two groups: those who received external beam radiation therapy alongside concomitant chemotherapy, followed by brachytherapy, with or without pembrolizumab during chemoradiation, followed by maintenance therapy. The median follow-up duration was 17.9 months.
The results revealed a significant improvement in PFS for patients who received pembrolizumab in conjunction with chemoradiotherapy compared to those who received a placebo (HR 0.70; 95% CI 0.55–0.89; p=0.0020). While the addition of pembrolizumab to chemoradiotherapy showed a favourable trend in OS (HR=0.73; 95% CI, 0.49-1.07), statistical significance was not reached. Importantly, the combination of immunotherapy and chemoradiation was deemed safe, with manageable toxicity and no decline in patients’ quality of life.
These results contrast with the negative findings from the phase III CALLA trial, which evaluated the PD-L1 inhibitor durvalumab in a similar setting. Prof Els Van Nieuwenhuysen emphasized the need for caution when comparing two different trials and highlighted potential differences that may account for varying outcomes. Discrepancies could stem from distinctions in sample sizes or patient risk profiles, and there may even be subtle differences in the mechanisms of action between PD-1 and PD-L1 inhibitors. However, definitive conclusions remain elusive.
Prof Gennigens referred to the positive results of the GCIG INTERLACE trial, which explored induction chemotherapy before concurrent chemoradiotherapy, prompting Prof Van Nieuwenhuysen to discuss her clinical approach. She mentioned her current practice of administering neoadjuvant chemotherapy, particularly for node-positive patients based on the STARS trial from 2021. However, she expressed her intention to modify the protocol by de-escalating chemotherapy after chemoradiation for this patient population. Furthermore, she advocated for a broader indication for adjuvant chemotherapy. Regarding immunotherapy, she maintained a cautious stance due to the negative CALLA trial results and highlighted the need for additional research on the combination of immunotherapy and radiotherapy. She also mentioned a preference for waiting until more mature OS data is available before considering longer maintenance therapy.
You may also be interested in:
With the educational support of:
 |
 |