Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell carcinoma after progression with previous immune checkpoint inhibitor treatment (CONTACT-03): a multicentre, randomised, open-label, phase 3 trial

Author(s): Prof Sumanta Kumar Pal, MD1;Laurence Albiges, MD2;Piotr Tomczak, MD3;Cristina Suárez, MD4;Martin H Voss, MD5;Guillermo de Velasco, MD6;Jad Chahoud, MD7;Anastasia Mochalova, MD8;Giuseppe Procopio, MD9;Hakim Mahammedi, MD10;Friedemann Zengerling, MD11;Chan Kim, MD12;Takahiro Osawa, MD13;Martín Angel, MD14;Suyasha Gupta, MEng15;Omara Khan, MSc16;Bo Liu, MS15;Guillaume Bergthold, MD20;Melania Kalaitzidou, PhD16;Mahrukh Huseni, MS15;Christian Scheffold, MD17;Prof Thomas Powles, MD18;Prof Toni K Choueiri, MD19
Source: DOI:https://doi.org/10.1016/S0140-6736(23)00922-4

Dr. Maen Hussein's Thoughts

Atezo and cabo is a NO.

BACKGROUND

Immune checkpoint inhibitors are the standard of care for first-line treatment of patients with metastatic renal cell carcinoma, yet optimised treatment of patients whose disease progresses after these therapies is unknown. The aim of this study was to determine whether adding atezolizumab to cabozantinib delayed disease progression and prolonged survival in patients with disease progression on or after previous immune checkpoint inhibitor treatment.

METHODS

CONTACT-03 was a multicentre, randomised, open-label, phase 3 trial, done in 135 study sites in 15 countries in Asia, Europe, North America, and South America. Patients aged 18 years or older with locally advanced or metastatic renal cell carcinoma whose disease had progressed with immune checkpoint inhibitors were randomly assigned (1:1) to receive atezolizumab (1200 mg intravenously every 3 weeks) plus cabozantinib (60 mg orally once daily) or cabozantinib alone. Randomisation was done through an interactive voice-response or web-response system in permuted blocks (block size four) and stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk group, line of previous immune checkpoint inhibitor therapy, and renal cell carcinoma histology. The two primary endpoints were progression-free survival per blinded independent central review and overall survival. The primary endpoints were assessed in the intention-to-treat population and safety was assessed in all patients who received at least one dose of study drug. The trial is registered with ClinicalTrials.gov, NCT04338269, and is closed to further accrual.

FINDINGS

From July 28, 2020, to Dec 27, 2021, 692 patients were screened for eligibility, 522 of whom were assigned to receive atezolizumab–cabozantinib (263 patients) or cabozantinib (259 patients). 401 (77%) patients were male and 121 (23%) patients were female. At data cutoff (Jan 3, 2023), median follow-up was 15·2 months (IQR 10·7–19·3). 171 (65%) patients receiving atezolizumab–cabozantinib and 166 (64%) patients receiving cabozantinib had disease progression per central review or died. Median progression-free survival was 10·6 months (95% CI 9·8–12·3) with atezolizumab–cabozantinib and 10·8 months (10·0–12·5) with cabozantinib (hazard ratio [HR] for disease progression or death 1·03 [95% CI 0·83–1·28]; p=0·78). 89 (34%) patients in the atezolizumab–cabozantinib group and 87 (34%) in the cabozantinib group died. Median overall survival was 25·7 months (95% CI 21·5–not evaluable) with atezolizumab–cabozantinib and was not evaluable (21·1–not evaluable) with cabozantinib (HR for death 0·94 [95% CI 0·70–1·27]; p=0·69). Serious adverse events occurred in 126 (48%) of 262 patients treated with atezolizumab–cabozantinib and 84 (33%) of 256 patients treated with cabozantinib; adverse events leading to death occurred in 17 (6%) patients in the atezolizumab–cabozantinib group and nine (4%) in the cabozantinib group.

INTERPRETATION

The addition of atezolizumab to cabozantinib did not improve clinical outcomes and led to increased toxicity. These results should discourage sequential use of immune checkpoint inhibitors in patients with renal cell carcinoma outside of clinical trials.

FUNDING

F Hoffmann-La Roche and Exelixis.

Author Affiliations

1Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA;2Department of Cancer Medicine, Institut Gustave Roussy, Villejuif, France;3Department of Oncology, Poznan University of Medical Sciences, Poznan, Poland;4Department of Medical Oncology, Vall d’Hebron Institute of Oncology, Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain;5Department of Medicine, Memorial Sloan Kettering Cancer Center, New6Medical Oncology Department, University Hospital 12 de Octubre, Madrid, Spain;7Department of Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA7;8Department of Chemotherapy, Clinical Hospital Number 1 MEDSI, Moscow, Russia;9Department of Medical Oncology, Fondazione Istituto Nazionale dei Tumori di Milano, Milan, Italy;10Department of Medical Oncology, Jean Perrin Center, Clermont-Ferrand, France;11Department of Urology and Pediatric Urology, University Hospital Ulm, Ulm, Germany;12Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, South Korea;13Department of Urology, Hokkaido University Hospital, Sapporo, Japan;14Department of Genitourinary Cancer, Instituto Alexander Fleming, Buenos Aires, Argentina;15Genentech, South San Francisco, CA, USA;16Roche Product, Welwyn Garden City, UK;17Exelixis, Alameda, CA, USA;18Barts Cancer Institute, Centre for Experimental Cancer Medicine, Queen Mary University of London, London, UK;19Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA;20F Hoffmann-La Roche, Basel, Switzerland;

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