According to patient-reported outcomes for those with endometrial cancer, the combination of lenvatinib plus pembrolizumab was favored over treatment of physician's choice.
The combination of lenvatinib (Lenvima) plus pembrolizumab (Keytruda) was favored in most patient-reported outcomes (PROs) compared with treatment of physician’s choice (TPC) in patients with advanced endometrial cancer, according to a post hoc analysis of time to deterioration of quality of life (QOL) presented at the European Society for Medical Oncology Gynaecological Cancers Congress 2022.1
This analysis looked at the time to first deterioration (TTFD), defined as the time to the first onset of an increase or decrease of 10 or more points from baseline, and time to definitive deterioration (TTDD), defined as the time to first onset of a difference of 10 or more points from baseline without a subsequent recovery from patients in the phase 3 KEYNOTE-775 study (NCT03517449).
Researchers found when evaluating PROs that neither treatment was favored for patients experiencing fatigue or nausea/vomiting at TTFD, explained Domenica Lorusso, MD, PhD, associate professor of obstetrics and gynecology at the Catholic University of Rome and head of clinical research at Fondazione Policlinico Gemelli IRCCS.
Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Endometrial Cancer Module (EORTC QLQ-EN24) and EORTC QLQ-30 questionnaires, they found a median TTFD for fatigue at 1.15 months (95% CI, 0.79-1.41) in the combination arm vs 1.38 months (95% CI, 1.02-1.41) in the TPC arm (HR, 1.16; 95% CI, 0.99-1.37). Similar outcomes were seen for nausea/vomiting with a median TTFD of 2.14 months (95% CI, 2.07-2.76) for patients in the lenvatinib plus pembrolizumab arm vs 2.10 months (95% CI, 1.64-2.79) for those in the TPC arm (HR, 1.08; 95% CI, 0.90-1.29).
Several other factors favored the combination arm, including dyspnea, poor body image, tingling/numbness, and hair loss. In comparison, physical functional scale, pain, appetite loss, diarrhea, and muscular pain were favored in the TPC arm.
In terms of TTDD, lenvatinib plus pembrolizumab was nominally favored on almost all scales compared with the TPC arm. For fatigue specifically, patients treated with lenvatinib and pembrolizumab had a median TTDD of 9.27 months (95% CI, 7.20-11.34) vs 3.48 months (95% CI, 2.73-4.17) in the TPC arm (HR, 0.48; 95% CI, 0.39-0.59). Moreover, the median TTDD was 20.14 months (95% CI, 16.66-NE) in the combination arm for patients who experienced nausea/vomiting vs 6.24 months in the TPC group (95% CI, 5.78-8.31) (HR, 0.42; 95% CI, 0.32-0.55).
In the KEYNOTE-775 study, patients were randomly assigned 1:1 to 20 mg of oral lenvatinib once a day plus 200 mg of pembrolizumab given intravenously (IV) every 2 weeks (n = 411) or TPC (n = 416). PROs were assessed on day 1 of each treatment cycle until the end of treatment. Overall, the mean observation period for PRO measures was longer in the combination arm than the TPC arm at 9.3 months and 4.3 months, respectively.
As previously reported, there were no substantial differences observed in the health-related QOL (HRQOL) scores between the 2 arms over the 12-week period.2 HRQOL scores were available for 80% of patients in the combination group compared with 62% in the chemotherapy arm.
Efficacy in the primary analysis in the overall population showed a median PFS of 7.2 months with lenvatinib and pembrolizumab compared with 3.8 months with chemotherapy (HR, 0.56; 95% CI, 0.47-0.66; P < .001). The median OS was 18.3 months in the combination arm vs 11.4 months in the TPC arm (HR, 0.62; 95% CI, 0.51-0.75; P < .001).
Almost all patients had adverse events (AEs) during treatment, with the most common being any-grade hypertension in 64% of the combination arm vs in 48.7% of the chemotherapy arm. Furthermore, grade 3 or higher AEs occurred in 88.9% of patients in the doublet arm vs in 72.7% on the TPC arm. Grade 5 AEs occurred in 5.7% of patients in the combination arm vs 4.9% of those who received chemotherapy.
“Although limited by the nature of the post hoc analysis and nominal statistics, this time to deterioration analysis suggests that lenvatinib and pembrolizumab is favored over chemotherapy,” Lorusso concluded.
1. Lorusso D, Colombo N, Casado Herraez A, et al. Time to deterioration in quality of life in patients (pts) with advanced (aEC) endometrial cancer treated with lenvatinib plus pembrolizumab (L+P) or treatment of physician’s choice (TPC). Ann Oncol. 2022;33(5):S391-S394. doi:10.1016/j.annonc.2022.04.038
2. Makker V, Colombo N, Casado Herráez A, et al; Study 309–KEYNOTE-775 Investigators. Lenvatinib plus pembrolizumab for advanced endometrial cancer. N Engl J Med. 2022;386(5):437-448. doi:10.1056/NEJMoa2108330