In the phase III KEYNOTE-826 trial, the addition of pembrolizumab to chemotherapy with or without bevacizumab resulted in improved overall survival and progression-free survival in patients with persistent, recurrent, or metastatic cervical cancer, when compared to placebo plus chemotherapy with or without bevacizumab. The patient-reported outcomes data were recently published in The Lancet Oncology and showed that the addition of pembrolizumab to chemotherapy did not negatively affect the health-related quality of life (HRQoL) of these patients. By improving survival while maintaining HRQoL, this therapy offers new hope for patients with this aggressive disease.
Cervical cancer patients with advanced or recurrent disease often experience severe symptoms that can negatively impact their health-related quality of life (HRQoL); including a decreased social wellbeing and social functioning, anxiety and depression. Moreover, the toxicity associated with treatments for cervical cancer can also have a detrimental effect on HRQoL. Consequently, the treatment goal for advanced or recurrent cervical cancer patients is to prolong life while preserving or improving HRQoL.
In the phase III KEYNOTE-826 trial, the addition of pembrolizumab, an anti-PD-1 monoclonal antibody, to chemotherapy with or without bevacizumab led to significant improvements in overall survival (OS) and progression-free survival (PFS) in patients with persistent, recurrent, or metastatic cervical cancer, compared to the placebo group. Notably, the treatment was well-tolerated with manageable toxicity. To evaluate whether or not these OS and PFS improvements were accompanied by changes in HRQoL, the patient-reported outcomes (PROS) were evaluated as prespecified secondary and exploratory endpoints in KEYNOTE-826.
The multicentre phase III KEYNOTE-826 trial included 617 adult patients (≥18 years) with persistent, recurrent, or metastatic cervical cancer not previously treated with systemic chemotherapy and not amenable to curative treatment. These patients were randomly assigned (1:1) to receive chemotherapy with either pembrolizumab (n=308) or placebo (n=309) with or without bevacizumab. Primary endpoints were OS and PFS. Patient-reported outcomes included, among others, the EORTC Quality-of-Life-questionnaire-Core 30 (QLQ-C30). Change from baseline in QLQ-C30 global health status (GHS)–quality of life (QoL) was a prespecified secondary endpoint and was assessed in the PRO full analysis population, i.e., all patients who received at least one dose of study treatment and completed at least one post-baseline PRO assessment.
In total, 587 (95%) of 617 patients received at least one dose of study treatment and completed at least one post-baseline PRO assessment. These patients were, therefore, included in the PRO analyses (pembrolizumab group, n=290; placebo group, n=297). At week 30, QLQ-C30 completion was reported in 69% vs. 57% of patients in the pembrolizumab and placebo groups, respectively. Compliance was 94% vs. 90%, respectively. The least squares mean change in QLQ-C30 GHS-QoL score from baseline to week 30 was -0.3 points in the pembrolizumab group and -1.3 points in the placebo group, with a between-group difference in least squares mean change of 1.0 point (95%CI: -2.7-4.7). Median time to true deterioration in GHS–QoL was not reached in the pembrolizumab group and was 12.9 months in the placebo group (HR[95%CI]: 0.84[0.65-1.09]). In total, 42% vs. 29% of patients in the pembrolizumab and placebo groups had improved GHS–QoL at any time during the study (p= 0.0003).
In conclusion, the addition of pembrolizumab to chemotherapy with or without bevacizumab did not negatively affect HRQoL. Along with the efficacy and safety results already reported, these data support the benefit of pembrolizumab and the value of immunotherapy in patients with recurrent, persistent, or metastatic cervical cancer.
Monk BJ, Tewari KS, Dubot C, et al. 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 randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2023;24(4):392-402.