Pembrolizumab/Axitinib Combo Represents Promising First-line Option for Papillary or Chromophobe mRCC

Pembrolizumab (Keytruda) plus axitinib (Inlyta) produced promising responses in patients with papillary or chromophobe metastatic renal cell carcinoma (mRCC), according to findings from a subgroup analysis of the I- RARE retrospective observational study (Meet-URO 23) presented during the 2022 ESMO Congress.

In the overall population of patients with non–clear cell mRCC treated with the doublet (n = 25), the overall response rate (ORR) was 36%, with all 9 responders experiencing a partial response (PR) to treatment. Forty percent of patients had stable disease, 8% experienced disease progression, and 4 patients were not evaluable. The disease control rate (DCR) was 86.3%.

Specifically, in 11 patients with chromophobe histology, 4 patients achieved a PR with pembrolizumab plus axitinib, 2 had stable disease, and 1 experienced disease progression. Among the 14 patients with papillary histology, 5 achieved a PR with the doublet, 8 had stable disease, and 1 experienced disease progression.

“Pembrolizumab plus axitinib could be an active and feasible first-line treatment option for patients with papillary or chromophobe mRCC,” lead study author Marco Stellato, MD, of the Medical Oncology Department at Fondazione IRCCS Istituto Nazionale dei Tumori di Milano in Milan, Italy, and colleagues, wrote in a poster presentation of the data.

Patients with non–clear cell RCC are generally excluded from randomized phase 3 clinical trials; this has led to a lack of therapeutic options for this patient population, which account for approximately 20% to 25% of all RCC cases. With the I-RARE observational study, investigators examined the safety and effectiveness of the pembrolizumab/axitinib combination as a first-line therapy option in patients with papillary or chromophobe mRCC.

To do this, investigators retrospectively collected data from patients with metastatic papillary or chromophobenon–clear cell RCC who were treated at 12 Italian referral centers adhering to the Meet-Uro group from December 2020 to April 2022. The data focused on baseline characteristics, ORR, DCR, progression-free survival (PFS), and adverse effects (AEs).

The median age of patients included on the trial was 68 years. Regarding disease risk per International Metastatic RCC Database Consortium criteria, 16% had a score of good, 60% had a score of intermediate, and 24% had a score of poor. Sixty percent of patients had received prior nephrectomy.

Seventy-two percent of patients had an ECOG performance of 0, 20% had a status of 1, and 8% had a status of 2. Forty percent of patients had synchronous metastatic disease. Sites of metastasis in the overall population included the bone (12%), liver (25%), lung (32%), and nodes (80%).

Additional data showed that among all patients who received pembrolizumab plus axitinib, the median PFS was 10.8 months (95% CI, 1.7-11.5).

Immune-related AEs led to interruption of full treatment in 11 patients (34.4%); these toxicities included grade 3 hepatitis (n = 5), grade 3 hypophysitis (n = 1), grade 3 diarrhea (n = 1), grade 3 pancreatitis (n = 1), and grade 3 asthenia (n = 1).

Twelve patients (37.5%) temporarily interrupted treatment with axitinib because of persistent grade 2 hand-foot syndrome or grade 2 hypertension.

Reference

Stellato M, Buti S, Maruzzo M, et al. Clinical outcome of patients with non-clear metastatic renal cell carcinoma treated with pembrolizumab-axitinib combination: NEMESIA (non-clear metastatic renal cell carcinoma pembrolizumab axitinib) study, a subgroup analysis of I-RARE observational study (Meet-URO 23a). Ann Oncol. 2022;33 (suppl 7):S660-S680. doi:10.1016/annonc/annonc1072