Lenvatinib plus pembrolizumab shows promise for RCC and other solid tumors
medwireNews: Phase 1b/2 study data show that combining the multitargeted tyrosine kinase inhibitor lenvatinib with pembrolizumab could be a promising treatment option for patients with advanced renal cell carcinoma (RCC) and selected other advanced solid tumor types.
The study, by Matthew Taylor (Oregon Health and Science University, Portland, USA) and colleagues, included 30 patients with metastatic RCC in addition to 23 with endometrial cancer, 22 with squamous cell carcinoma of the head and neck (SCCHN), 21 each with melanoma and non-small-cell lung cancer (NSCLC), and 20 patients with urothelial cancer.
In the phase1b part of the trial, the researchers determined that the maximum tolerated dose for lenvatinib, which targets VEGFR1–3, FGFR1–4, PDGFRα, RET, and KIT, was 20 mg/day orally. This dose was used in combination with intravenous pembrolizumab 200 mg every 3 weeks for the phase 2 study.
Taylor and team report in the Journal of Clinical Oncology that patients with RCC showed the most promising response to the treatment in phase 2, with an objective response rate (ORR) of 63% at 24 weeks and 70% overall, and a median progression-free survival (PFS) time of 19.8 months.
Among the other tumor types treated in the current study, the ORR at 24 weeks was 52% for endometrial cancer, 48% for melanoma, 36% for SCCHN, 33% for NSCLC, and 25% for urothelial cancer. The corresponding median PFS durations were 9.7, 5.5, 4.7, 5.9, and 5.4 months.
The researchers say the “encouraging response rates” compare favorably with those observed in trials where each drug was given as monotherapy. For example, lenvatinib monotherapy previously resulted in an ORR of 27% in the second-line treatment of RCC, while first-line pembrolizumab showed an ORR of 34% in patients with advanced clear-cell RCC.
Taylor et al also found that there were no unexpected adverse events (AEs) and the AE profiles were similar across the tumor types.
Treatment-related (TR)AEs led to discontinuation in 16% of patients and to dose reductions and interruptions in 64% and 70%, respectively, but the authors comment that starting lenvatinib at a high dose and then reducing it where necessary “allows for strong inhibition of VEGF for several months before dose reduction,” which may “contribute to the efficacy” of the drug.
Around two-thirds (67%) of patients experience a grade 3 or 4 TRAE, most commonly hypertension (20%), fatigue (12%), diarrhea (9%), proteinuria (8%), and increased lipase levels (7%). There were two treatment-related deaths, one pulmonary hemorrhage in a patient with NSCLC and one gastrointestinal hemorrhage in a patient with urothelial cancer.
Based on the results of this study, the combination of lenvatinib plus pembrolizumab is now being tested in phase 3 trials among patients with RCC, endometrial cancer, melanoma, and NSCLC, and is also being explored in patients with gastric cancer, gastroesophageal cancer, and differentiated thyroid cancer.
In addition, Taylor and co-investigators “plan to study lenvatinib plus pembrolizumab in patients with RCC who have had disease progression after treatment with immune checkpoint inhibitors.”
medwireNews is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature group