KEY TAKEAWAYS
- The phase 3 KEYNOTE-826 trial registered as NCT03635567 aimed to assess the effect of pembrolizumab on overall and progression-free survival in patients.
- Patients were randomly assigned in a double-blind manner to receive chemotherapy with or without bevacizumab, along with either pembrolizumab or a placebo, for up to 35 cycles.
- The trial found that patients who received pembrolizumab along with chemotherapy had improved OS and PFS compared to those who received chemo alone or with a placebo.
- The PRO complete analysis population consisted of 587 patients who had received at least one dose of study treatment and completed at least one post-baseline PRO evaluation.
- The study revealed that adding pembrolizumab to chemotherapy with or without bevacizumab improved overall survival and progression-free survival in patients with persistent.
Patients with persistent, recurrent, or metastatic cervical cancer improved overall survival and progression-free survival (primary endpoints) when the anti-PD-1 monoclonal antibody pembrolizumab was added to chemotherapy with or without bevacizumab in the KEYNOTE-826 study, with tolerable adverse effects. A total of 151 cancer treatment facilities in 19 countries participated in the randomized phase 3 KEYNOTE-826 experiment. Patients who are 18 years or older along with a performance status of 0 or 1 on the Eastern Cooperative Oncology Group scale, and have cervical cancer that has persisted, returned, or spread metastatically without prior systemic chemotherapy (previous radio-sensitizing chemotherapy was allowed). Patients received chemotherapy (paclitaxel 175 mg/m2 plus cisplatin 50 mg/m2 or carboplatin area under the curve 5 mg/mL per min, intravenously) with or without bevacizumab (15 mg/kg every 3 weeks intravenously). They were randomly assigned (1:1) centrally via an interactive voice response system in a double-blind manner for up to 35 cycles. PD-L1 combined positive score, planned use of bevacizumab, and metastatic disease at diagnosis guided the randomization (block size = 4). Treatment group allocations were concealed from patients, researchers, and anyone else engaged in the study’s administration of treatments or clinical assessments of patients. Pretreatment measurements were taken on the EuroQol-5 dimension-5 level (EQ-5D-5L) visual analog scale, the EORTC Quality-of-Life-Core 30 (QLQ-C30), and the EORTC cervical cancer module (QLQ-CX24). Overall survival (OS) and progression-free survival (PFS) were the primary outcomes, as judged by investigators using RECIST version 1.1. The PRO complete analysis population (all patients who received at least one dose of trial treatment and completed at least one post-baseline PRO assessment) was evaluated for change from baseline in QLQ-C30 global health status (GHS)-the quality of life (QoL), a prespecified secondary outcome. The remaining PRO analyses were designated as exploratory endpoints in the protocol.
A total of 617 (pembrolizumab group, n=308; placebo group, n=309) of the 883 patients screened between November 20, 2018, and January 31, 2020, were randomly allocated. To be included in the PRO analysis, 587 (95%) of 617 patients needed to have received at least one dose of study treatment and completed at least one post-baseline PRO evaluation (pembrolizumab group, n=290; placebo group, n=297). The average time between visits was 22.0 months (interquartile range [IQR]: 19.1-24.4). At week 30, 199 (69%) of 290 patients on pembrolizumab and 168 (57%) of 297 patients on placebo had completed the QLQ-C30, corresponding to 94% and 90% compliance rates. The least squares mean change in QLQ-C30 GHS-QoL score between baseline and week 30 was -0.3 points (95% CI -3.1 to 2.6) in the pembrolizumab group and -1.3 points (-4.2 to 1.7) in the placebo group, with a difference of 10 points (95% CI -2.7 to 4.7) between the groups. In the group treated with pembrolizumab, the median time to the onset of a clinically meaningful decline in GHS-QoL was not attained (NR; 95% CI 13.4 months-NR), while in the placebo group, it was 12 months (range, 6.6 months to NR; hazard ratio, 0.84). Improvements in GHS-QoL were seen in 122 (42%) of 290 participants in the pembrolizumab group and 85 (29%) of 297 patients in the placebo group at any moment during the study (P=00003). The study revealed that pembrolizumab in combination with chemotherapy did not worsen the quality of life in patients with cervical cancer, supporting its efficacy and value in this setting.
Source:https://pubmed.ncbi.nlm.nih.gov/36878237/
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT03635567
Monk BJ, Tewari KS, Dubot C, Caceres MV, Hasegawa K, Shapira-Frommer R, Salman P, Yañez E, Gümüş M, Hurtado de Mendoza MO, Samouëlian V, Castonguay V, Arkhipov A, Tekin C, Li K, Martin Nguyen A, Monberg MJ, Colombo N, Lorusso D. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomized, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):392-402. doi: 10.1016/S1470-2045(23)00052-9. Epub 2023 Mar 3. PMID: 36878237.
