Frontline immune checkpoint inhibitor-based combination therapy in metastatic renal cell carcinoma patients with poor performance status.

Immune checkpoint inhibitor-based combination therapy (ICI-based combination) is a new standard of care for metastatic clear cell renal cell carcinoma (mRCC) in the frontline setting. Patients with poor performance status (PS) (≥2) were excluded from pivotal trials. Hence, the activity and safety of ICI-based combination therapy in this group of patients is still unknown.

We performed a multicentre retrospective study of PS ≥2 mRCC patients who received frontline ICI-based combination, either nivolumab-ipilimumab (NI) or pembrolizumab-axitinib (AP). Patients' characteristics, clinical outcomes, and toxicity were collected. We analysed overall response rate (ORR), median progression-free survival (mPFS), median overall survival (mOS) and grade ≥3 adverse events (G ≥ 3AEs). The association between the predictive biomarker IPI (immune prognostic index) and ORR/PFS/OS was also evaluated.

We identified 70 mRCC patients with PS ≥2 treated with ICI-based combination across 14 institutions between October 2017 and December 2021, including 45 and 25 patients were treated with NI and AP, respectively. Median age at diagnosis was 63 years, 51 (73%) were male, only 17 (24%) had prior nephrectomy, 50 (71%) had synchronous metastatic disease at diagnosis, and 16 (23%) had brain metastases. Sixty-one (87%) and 9 (13%) patients had ECOG (Eastern Cooperative Oncology Group) PS 2 and 3, respectively, and 25 (36%) and 45 (64%) patients were intermediate and poor International Metastatic RCC Database Consortium (IMDC) risk, respectively. Among all, 91% were clear cell RCC, 7 patients had sarcomatoid features. At the time of the analysis (median follow-up 11.1 months), 41% patients were dead. Median PFS and mOS in the entire cohort were 5.4 months and 16.0 months, respectively; ORR was 31%. No significant differences in ORR, PFS, OS, or G ≥3AEs were seen between NI and AP. The intermediate and poor IPI groups were significantly associated with reduced ORR and shorter PFS.

We report the first cohort of PS ≥2 mRCC patients treated with frontline ICI-based combination therapy. The survival outcomes in our cohort were inferior to that reported in pivotal trials. No significant differences in ORR, PFS, OS or toxicity were seen between NI and AP. Prospective real-world studies are needed to confirm these results.

European journal of cancer (Oxford, England : 1990). 2022 Nov 26 [Epub ahead of print]

Lucía Carril-Ajuria, Emeline Colomba, Carmen Romero-Ferreiro, Luigi Cerbone, Raffaele Ratta, Philippe Barthelemy, Clarisse Vindry, Aude Fléchon, François Cherifi, Elouen Boughalem, Claude Linassier, Giuseppe Fornarini, Sara E Rebuzzi, Marine Gross-Goupil, Carolina Saldana, Maricruz Martin-Soberón, Guillermo de Velasco, Ray Manneh, Cristina Pernaut, Ana Sanchez de Torre, Ronan Flippot, Bernard Escudier, Laurence Albiges

Medical Oncology Department, Institute Gustave Roussy, Villejuif, France., Instituto de Investigacion Sanitaria, Hospital 12 de Octubre (imas12), Madrid, Spain; Faculty of Health Sciences, Universidad Francisco de Vitoria, 28223 Madrid, Spain., Medical Oncology, Foch Hospital, Suresnes 92151, France., Medical Oncology, Hôpitaux Universitaires de Strasbourg/ICANS, Strasbourg, France., Medical Oncology, Centre Léon Bérard, 69008 Lyon, France., Medical Oncology, Centre François Baclesse, Caen, France., Medical Oncology, Institut de Cancerologie de l'Ouest, 49055 Angers, France., Medical Oncology, Centre Hospitalier Universitaire de Tours, Tours, France., Medical Oncology, U.O. Oncologia Medica 1 RCCS Ospedale Policlinico San Martino, Genova, Italy., Medical Oncology, Centre Hospitalier Universitaire Saint-André, Bordeaux, France., Medical Oncology, Hôpital Henri Mondor, APHP, Univ Paris Est Creteil, Créteil, France., Medical Oncology, University Hospital 12 de Octubre, Madrid, Spain., Sociedad de Oncología y Hematología del Cesar, Valledupar, Colombia., Medical Oncology, University Hopital Severo Ochoa, Leganés, Madrid, Spain., Medical Oncology, University Hospital Infanta Cristina, Parla, Madrid, Spain., Medical Oncology Department, Institute Gustave Roussy, Villejuif, France. Electronic address: .