Pembrolizumab Plus Axitinib for Metastatic Papillary and Chromophobe Renal Cell Carcinoma: NEMESIA (Non Clear MEtaStatic Renal Cell Carcinoma Pembrolizumab Axitinib) Study, a Subgroup Analysis of I-RARE Observational Study (Meet-URO 23a)

Abstract

Non-clear cell renal cell carcinoma (nccRCC) represents a heterogeneous histological group which is 20–25% of those with renal cell carcinoma (RCC). Patients with nccRCC have limited therapeutic options due to their exclusion from phase III randomized trials. The aim of the present study was to investigate the effectiveness and tolerability of pembrolizumabaxitinib combination in chromophobe and papillary metastatic RCC (mRCC) patients enrolled in the I-RARE (Italian Registry on rAre genitor-uRinary nEoplasms) observational ongoing study (Meet-URO 23). Baseline characteristics, objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) and toxicities were retrospectively and prospectively collected from nccRCC patients treated in 14 Italian referral centers adhering to the Meet-Uro group, from December 2020 to April 2022. Only patients with chromophobe and papillary histology were considered eligible for the present pre-specified analysis. There were 32 eligible patients who received pembrolizumab-axitinib as first-line treatment, of whom 13 (40%) had chromophobe histology and 19 (60%) were classified as papillary RCC. The DCR was 78.1% whereas ORR was 43.7% (11 patients achieved stable disease and 14 patients obtained partial response: 9/19 papillary, 5/13 chromophobe). Six patients (18.7%) were primary refractory. Median PFS was 10.8 months (95%CI 1.7–11.5). Eleven patients (34.3%) interrupted the full treatment due to immune-related adverse events (irAEs): G3 hepatitis (n = 5), G3 hypophisitis (n = 1), G3 diarrhea (n = 1), G3 pancreatitis (n = 1), G3 asthenia (n = 1). Twelve patients (37.5%) temporarily interrupted axitinib only due to persistent G2 hand-foot syndrome or G2 hypertension. Pembrolizumab-axitinib combination could be an active and feasible first-line treatment option for patients with papillary or chromophobe mRCC.

Advanced Non-Clear Cell Renal Cell Carcinoma Treatments and Survival: A Real-World Single-Centre Experience

“…In our findings, patients who were treated with a first-line immunotherapy combination had a PFS of 12.7 months and an ORR of 42.4%. These results are in line with those reported in the prospective trials described above but, more importantly, are similar to those recently reported in two real-world experiences [25,45]. Furthermore, we can also report that patients who received immunotherapy in their history achieved longer OS than those who did not.…”

Advances in non‐clear cell renal cell carcinoma management: From heterogeneous biology to treatment options

“…90 91 Similarly, the combination of pembrolizumab plus axitinib has shown activity in pRCC and chRCC, demonstrating a DCR of 78.1%, ORR 43.7% (9/11 in pRCC, 5/13 in chRCC) with median PFS 10.8 months. 92 These results are promising for the efficacy of TKI and ICI combinations in the future.…”

“…Preliminary findings from the phase II KEYNOTE‐B61 trial were presented at the 2022 European Society of Medical Oncology meeting, including 51 patients with pRCC, 15 with chRCC, 7 with unclassified nccRCC, 5 with tRCC and 4 “others.” At median follow‐up of 8.2 months and across IMDC risk‐categories, this regimen yielded an ORR of 47.6% (3.7% CR, 43.9% PR) and DCR(including SD) of 79.3%, with 6‐month PFS and OS rates of 72.3% and 87.8%, respectively 91 . Similarly, the combination of pembrolizumab plus axitinib has shown activity in pRCC and chRCC, demonstrating a DCR of 78.1%, ORR 43.7% (9/11 in pRCC, 5/13 in chRCC) with median PFS 10.8 months 92 . These results are promising for the efficacy of TKI and ICI combinations in the future.…”

Pathological Complete Response to Pembrolizumab plus Axitinib Combination following Serious Immune-Related Adverse Events in an Advanced Renal Cell Carcinoma Patient with a History of Rheumatoid Arthritis

“…ICI-based combinations are nowadays the preferred treatment option for advanced RCC, with rates of objective responses ranging from 39% to 71% and rates of complete responses ranging from 6% to 16% [3‒6, 13, 14]. Moreover, a correlation between depth of response and survival outcomes was observed in large randomized phase 3 trials [4, 15].…”