The addition of pembrolizumab to standard chemotherapy has demonstrated substantial survival benefits for patients with advanced cervical cancer, according to the final analysis of the phase 3 KEYNOTE-826 trial (NCT03635567) published in Annals of Oncology. The study reveals significant improvements in both overall survival (OS) and progression-free survival (PFS) across different patient subgroups.
Significant Survival Benefits Observed
Patients receiving bevacizumab alongside pembrolizumab and chemotherapy showed particularly impressive results. The median PFS reached 15.2 months in the pembrolizumab arm compared to 10.2 months in the placebo arm (HR, 0.57; 95% CI, 0.45-0.73). More notably, the median OS extended to 37.6 months versus 22.5 months (HR, 0.61; 95% CI, 0.47-0.80), with 24-month OS rates of 61.2% and 46.1%, respectively.
Even in patients who did not receive bevacizumab, the combination therapy showed meaningful improvements. The median OS was 17.1 months in the pembrolizumab group versus 12.6 months in the placebo group (HR, 0.67; 95% CI, 0.49-0.91), with 24-month OS rates of 36.1% and 26.2%, respectively.
Trial Design and Patient Population
The study randomized patients 1:1 to receive either pembrolizumab (200 mg intravenously every three weeks for up to 35 cycles) or placebo, combined with standard chemotherapy. The chemotherapy regimen consisted of paclitaxel (175 mg/m²) plus either cisplatin (50 mg/m²) or carboplatin. Some patients also received bevacizumab (15 mg/kg) every three weeks based on investigator decision.
Dr. Domenica Lorusso, professor and director of the Operative Unit of Gynecological Oncology at Humanitas San Pio X, emphasized the clinical significance: "The addition of pembrolizumab to chemotherapy resulted in clinically meaningful improvements in PFS and OS compared with placebo plus chemotherapy regardless of concomitant bevacizumab use."
Safety Profile and Tolerability
The safety analysis revealed manageable adverse events across treatment groups. Among patients receiving bevacizumab, treatment-related adverse events (TRAEs) occurred in 97.4% of the pembrolizumab arm versus 98.4% in the placebo arm, with grade 3 or higher events in 74.0% and 66.8%, respectively.
For patients not receiving bevacizumab, TRAEs were reported in 96.4% of the pembrolizumab group and 94.8% of the placebo group, with grade 3 or higher events occurring in 60.4% and 62.1%, respectively. While treatment discontinuations were observed, they were generally consistent with the known safety profiles of these therapies.
Clinical Implications
These findings represent a significant advancement in the treatment landscape for persistent, recurrent, or metastatic cervical cancer. The study demonstrates that the addition of pembrolizumab to standard chemotherapy provides substantial survival benefits while maintaining a manageable safety profile, potentially establishing a new standard of care for this patient population.
