medwireNews: Research suggests that patients with metastatic clear cell renal cell carcinoma (ccRCC) with disease progression after immune checkpoint inhibitor (ICI) therapy may benefit from the combination of lenvatinib and pembrolizumab.
The interim analysis of the phase 2 expansion cohort of the Study 111/KEYNOTE-146 trial was presented at the virtual 2020 ASCO Annual Meeting by Chung-Han Lee, from Memorial Sloan Kettering Cancer Center in New York, USA.
“Lenvatinib plus pembrolizumab demonstrated promising antitumor activity in patients with metastatic clear cell renal cell carcinoma who had previously progressed on prior PD-1/PD-L1 therapy,” he said.
Chung-Han Lee reports the final analysis of KEYNOTE-146/Study 111 trial (4:57)
The presenter reminded delegates that the trial’s phase 1b interim analysis of 30 patients without prior ICI therapy gave an objective response rate (ORR) of 70% and a median progression-free survival (PFS) of 20 months.
The current cohort included 104 patients aged a median of 60 years who had experienced disease progression after receiving a PD-1 or PD-L1 inhibitor for a median of 7 months; 65% of the group had also received a VEGF inhibitor, and 37% had been given nivolumab plus ipilimumab.
The cohort included patients with MSKCC favorable- (36%), intermediate- (42%), and poor-risk (22%) disease, and 75% had previously undergone nephrectomy. In addition, 42% of patients had a combined positive score for PD-L1 of at least 1%, 41% were negative with a score below 1%, and 16% had an unknown status.
Lenvatinib 20 mg/day plus pembrolizumab 200 mg every 3 weeks achieved a 24-week ORR as per the immune-related RECIST criteria of 51% and an overall ORR of 55%, with all responses partial. The median duration of response was 12 months.
The 12-month rate of PFS was 45%, with a median value of 11.7 months, and the corresponding values for overall survival were 77% and not reached, Lee said.
When patients were collated into subgroups by previous treatment, the ORR was 55% for those given only PD-1 or PD-L1 inhibitors, and 59% and 47% for patients who had also received a VEGR inhibitor or nivolumab plus ipilimumab, respectively. The median durations of response in these groups were 12 months, 9 months, and not reached, respectively.
“The majority of patients who achieved an objective response remain on ongoing therapy with lenvatinib plus pembrolizumab, even after experiencing prior VEGF-targeted therapy,” Lee said.
“Similarly, the majority of patients who achieved an objective response remain on ongoing therapy, even in the nivolumab–ipilimumab refractory setting.”
Safety analysis indicated that 12% of patients discontinued lenvatinib and 12% pembrolizumab because of treatment-related adverse events (TRAEs). Lenvatinib dose reductions were required after a median of 2 months by 14% of patients because of fatigue and 10% because of diarrhea, while 9% discontinued because of proteinuria.
The most common TRAEs at grade 3 were hypertension (19%), diarrhea (9%), and proteinuria (8%), followed by fatigue (5%) and nausea (2%). Grade 4 TRAEs included lipase elevation, diverticulitis, large intestinal perforation, and myocardial infarction, and there were two grade 5 events, namely upper gastrointestinal hemorrhage and sudden death.
“The adverse events were manageable and consistent with the observed adverse event profile of other studies,” Lee summarized.
He concluded that a phase 3 study is now underway to assess lenvatinib and pembrolizumab as a first-line option for advanced RCC patients.
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This independent news story was supported by an educational grant from Pfizer and Merck KGaA
2020 ASCO Annual Meeting; 29–31 May