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FDA Grants Pembrolizumab/Lenvatinib Breakthrough Designation for RCC

Jason M. Broderick @jasoncology
Published: Tuesday, Jan 09, 2018

Dr. Roy Baynes
Roy Baynes, MD, PhD
The FDA has granted the combination of the PD-1 inhibitor pembrolizumab (Keytruda) and the VEGF/FGF inhibitor lenvatinib (Lenvima) a breakthrough therapy designation for the treatment of patients with advanced and/or metastatic renal cell carcinoma (RCC).

ORR at 24 weeks was 83% (95% CI, 52-98) in the treatment-naïve cohort, and 50% in those patients who received previous treatment. All responses were partial responses. Two patients in the treatment-naïve group and 8 in the previously-treated population had stable disease. One patient in each cohort had primary progressive disease.

The median duration of response was not yet reached for the total cohort and the treatment-naïve cohort. The median duration of response was 8.5 months in the pretreated cohort.

When stratified by PD-L1 staining status, “objective responses could be seen in both the PD-L1–positive and PD-L1–negative populations, and appear to be similar, with 58% of the PD-L1-positive patients and 71% of PD-L1-negative patients achieving objective responses,” lead author Chung-Han Lee, MD, PhD, a medical oncologist at Memorial Sloan Kettering Cancer Center, said when reporting the results at the 2017 ESMO Congress.

At the time of data cutoff, the median progression-free survival (PFS) had not yet been reached (95% CI, 9.9 months-not evaluable). Tumor responses assessed by a modified RECIST v1.1 were the same as with irRECIST. The median PFS by RECIST v1.1 was also not yet evaluable.

Ten of 12 patients in the treatment-naïve cohort remain on treatment.

“An extended duration of response could be seen in both PD-L1–positive and PD-L1–negative patients,” Lee said. “In the treatment-naïve cohort, prolonged stable disease could also be seen in PD-L1–positive patients who remained still on therapy at 12 months. In the previously treated patients, 6 of 18 patients remain on treatment, with 1 patient having a duration of response >8 months.”

Twenty-eight of 30 patients experienced tumor shrinkage, and Lee said there was a tendency for greater tumor shrinkage in the treatment-naïve patients. Tumor shrinkage was observed in both PD-L1–positive and PD-L1–negative patients, with no clear association between changes in tumor size and PD-L1 staining status.

Treatment-emergent adverse events (TRAEs) led to lenvatinib dose reductions in 18 patients. Five patients (17%) discontinued at least 1 study drug.

The most common TRAEs of any grade were diarrhea (83%), fatigue (70%), hypothyroidism (67%), stomatitis (60%), hypertension (57%), and nausea (57%). No new safety signals were found. The 2 grade-5 TRAEs were related to disease progression and not considered related to the study drugs.
Lee C, Makker V, Rasco D, et al. A phase 1b/2 trial of lenvatinib plus pembrolizumab in patients with renal cell carcinoma. Presented at ESMO 2017 Congress; September 8-12, 2017; Madrid, Spain. Abstract 847O.


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