Pembrolizumab Quadruplet Does Not Deteriorate HRQOL in Advanced Cervical Cancer

Bradley J. Monk, MD

Treatment with the FDA-approved combination of pembrolizumab (Keytruda) plus chemotherapy with or without bevacizumab (Avastin) does not have a negative impact on health-related quality-of-life (HRQOL), according to new findings from KEYNOTE-826 (NCT03635567).¹

Overall, the change from baseline in quality-of-life (QOL) was -0.3 (95% CI, -3.1 to 2.6) with the pembrolizumab combination vs -1.3 (95% CI, -4.2 to 1.7) with placebo plus chemotherapy (HR, 1.0; 95% CI, -2.7 to 4.7; P = .60). In terms of physical function, the mean change from baseline was -8.3 (95% CI, -11.1 to -5.5) with pembrolizumab/chemotherapy vs -6.1 (95% CI, -9.0 to -3.2) with placebo plus chemotherapy (HR, -2.1; 95% CI, -6.0 to 1.8; P = .28).

Mean change from baseline in the visual analog score (VAS) was 0.3 (95% CI, -2.2 to 2.8) with thepembrolizumab combination vs -1.5 (95% CI, -4.1 to 1.1) with placebo (HR, 1.8; 95% CI, -1.6 to 5.1; P = .29).

“This study shows that more intensive therapy helps women not only live longer but prevents deterioration and numerically improves quality-of-life. This is particularly impactful given the young age of those battling stage 4B, persistent and recurrent cervical cancer,” said Bradley J. Monk, MD, a gynecologic oncologist, and director of GOG Partners at The GOG Foundation, Inc. told Targeted Oncology™.

Pembrolizumab added to paclitaxel and cisplatin or paclitaxel and carboplatin with or without bevacizumab was approved by the FDA in 2021, based on efficacy and safety findings from KEYNOTE-826. In 548 patients with persistent, recurrent, or metastatic cervical cancer, the combination showed a median progression-free survival (PFS) of 10.4 months vs 8.2 months with placebo (HR, 0.62; 95% CI, 0.53-0.79; P < .0001). In addition, the combination achieved a 24-month overall survival (OS) of 53.0% vs 41.7% with placebo (HR, 0.58; 95% CI, 0.44-0.77; P < .0001).²

Krishnansu S. Tewari, MD

The median treatment duration was 10.0 months in the quadruplet arm of KEYNOTE-826, and toxicities occurred in 99.3% of patients. However, HRQOL did not decrease in patients treated in the study.

“Because up to 65% of patients were treated with quadruplet therapy, we learned that with even 4 medicines, the statistically significant and clinically meaningful improvements in progression-free survival [PFS] and overall survival [OS] were not accompanied by a significant deterioration in quality of life, Krishnansu S. Tewari, MD told Targeted Oncology™.

To assess HRQOL, KEYNOTE-826 investigators used multiple QOL scoring tools to collect patient-reported outcomes (PROs) data.¹

“The most important measures in this study to measure quality of life were the EORTC Quality-of-Life-Core 30 [QLQ-C30], the EORTC Cervical Cancer module [QLQ-CX24], and the EuroQol [EQ)-5D-5L] VAS. Each were collected before treatment at cycles 1-14 and every other cycle thereafter,” explained Tewari, a gynecologic oncologists and professor in the Division of Gynecologic Oncology, Obstetrics, & Gynecology School of Medicine, at the University of California, Irvine.

Overall, 279 patients in the pembrolizumab quadruplet arm and 283 in the placebo arm responded to the HRQOL questionnaire. Results showed that the mean QLQ-C30 GHS–QOL score at baseline among those treated with the pembrolizumab combination was 23.3% vs 21.9% in the placebo group. At week 30, the mean score was 21.4%% in the pembrolizumab arm vs 18.5% in the placebo arm. In terms of QLQ-C30, which measures patients’ physical function, the mean score at baseline was 23.0% in the pembrolizumab group vs 20.9% in the placebo group. At week 30, the mean score was 23.5% vs 20.4%, respectively.

In terms of VAS, which was measured with the EQ-5D-5L VAS tool, the mean score at baseline was 21.3% in the pembrolizumab arm compared with 20.2% in the placebo arm. At week 30, the mean score was 19.4% in the pembrolizumab vs 18.9% in the placebo arm.

The time to deterioration (TTD) on the QLQ-C30 GHS–QoL scale was at 12 months was 57.3% with the pembrolizumab combination vs 51.1% with placebo (HR, 0.84; 95% CI, 0.65-1.09; P = .19). On the QLQ-C30 physical functioning scale, the TTD at 12 months was 49.1% with pembrolizumab vs 48.5% with placebo (HR, 1.11; 95% CI, 0.87-1.42; P = .39). Among patients evaluated on the EuroQol-5 scale, the TTD at 12 months was 58.2% with pembrolizumab vs 44.8% with placebo (HR, 0.75; 95% CI, 0.58-0.97; P = .027).

Overall, the findings from the PROs analysis support the benefit of pembrolizumab plus chemotherapy with or without bevacizumab.

“The FDA is particularly interested in patient safety, and QOL has emerged as an important prognostic factor in diseases such as incurable cervical cancer. The QOL data were likely to have figured in their decision to grant approval to first-line chemotherapy plus pembrolizumab with or without bevacizumab for PD-L1-positive cervical cancer in the recurrent/metastatic space,” said Tewari.

_REFERENCES:

_{1. Colombo N, Dubot C, Lorusso D, et al. Pembrolizumab for persistent, recurrent, or metastatic cervical cancer. N Engl J Med. 2021; 385:1856-1867. doi:10.1056/NEJMoa2112435}

_{2. 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. doi:10.1016/S1470-2045(23)00052-9}