Pembrolizumab plus lenvatinib delivers antitumour response against nonclear cell RCC

Pembrolizumab (pembro) plus lenvatinib (lenva) provides durable antitumour activity in patients with advanced nonclear cell renal cell carcinoma (nccRCC) and has a manageable safety profile, according to the results of the phase II KEYNOTE-B61 study.

“These results continue to support pembro+lenva as a first-line treatment option for patients with variant histologies of nccRCC,” said first author Martin H Voss from the Memorial Sloan Kettering Cancer Center in New York, US.

Based on the findings of the phase III KEYNOTE-581/CLEAR study, pembro+lenva was approved as a first-line treatment for advanced/metastatic RCC. Previous results from the phase II KEYNOTE-B61 study with a median follow-up of 15 months backed the use of first-line pembro+lenva in nccRCC patients.

“We now report updated results from KEYNOTE-B61 with median follow-up of 23 months,” Voss said.

In the current study, adult patients with previously untreated, advanced nccRCC and measurable disease per RECIST v1.1 received pembro 400 mg IV Q6W for ≤18 cycles for approximately 2 years and lenva 20 mg orally once daily until intolerable toxicity, disease progression, or patient withdrawal from the study.

Objective response rate (ORR) per RECIST v1.1 by blinded independent central review (BICR) was the primary endpoint, while disease control rate (DCR), duration of response (DOR), and progression-free survival (PFS) per RECIST v1.1 by BICR, overall survival (OS), and safety were secondary.

Overall, 158 patients (median age 60 years) were treated with pembro+lenva. The most common histologic variant of RCC was papillary (n=93, 59 percent), followed by chromophobe (n=29, 18 percent) and unclassified (n=20, 13 percent). [ASCO GU 2024, abstract 2]

Of the patients, 86 discontinued treatment primarily because of disease progression (n=56, 35 percent). Median time from the first dose to data cutoff (5 July 2023) was 22.8 months.

Treatment response

Nearly half of the patients showed an objective response (ORR, 51 percent, 95 percent confidence interval [CI], 43‒59; complete response: n=13, 8 percent; partial response: n=67, 42 percent). The DCR stood at 82 percent (95 percent CI, 75‒88). Median DOR was 19.5 months (range, 15.2‒not reached [NR]). About 51 percent of response lasted for ≥18 months.

In terms of survival, PFS was 17.9 months (95 percent CI, 15.1‒22.1) while OS was NR. At 18 months, the estimated PFS and OS rates were 48 percent and 73 percent, respectively.

Most the patients (n=151, 96 percent) experienced a treatment-related adverse event (TRAE). The most common TRAE was hypertension (56 percent), followed by diarrhoea (46 percent), hypothyroidism (41 percent), and proteinuria (30 percent).

In addition, 92 patients (58 percent) had grade 3‒4 TRAEs, the most frequent of which were hypertension (25 percent), diarrhoea (5 percent), proteinuria (5 percent), and weight loss (5 percent). No TRAE-related deaths were reported. Discontinuation due to TRAE was 15 percent for pembro, 13 percent for lenva, and 4 percent for pembro+lenva.