Immune checkpoint inhibitors are a type of immunotherapy. These targeted drugs block different checkpoint proteins that stop the immune system from unleashing an attack on cancer cells. The most frequently used class of these agents are programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) checkpoint inhibitors.

After prior progression on these therapies, a potential strategy is to rechallenge patients with PD-(L)1 inhibitors, but the clinical benefit of this novel approach has not yet been established.

“The use of immune checkpoint inhibitors in combination has become first-line standard treatment for metastatic renal cell carcinoma and has dramatically improved outcomes in metastatic renal cell carcinoma. However, optimized treatment of patients whose disease unfortunately progresses after these therapies is unknown,” says Cristina Suarez, Clinical Investigator of the Vall d’Hebron Institute of Oncology’s (VHIO) Genitourinary, Central Nervous System (CNS) Tumors, Sarcoma and Cancer of Unknown Primary Site Group, and co-author of this present study (1).

Led by first author of this study Toni K. Choueiri at the Dana Farber Cancer Institute, Harvard Medical School in Boston (USA), the international phase III, randomized, open-label CONTACT-03 trial was designed to assess PD-(L)1 therapy rechallenge in patients with advanced solid tumors. The study compared cabozantinib—a multi-kinase inhibitor —alone versus cabozantinib plus PD-L1 inhibitor atezolizumab in patients with advanced kidney cancer who had previously progressed on a PD-L(1) inhibitor.

“This is the first randomized phase III trial to evaluate the efficacy and safety of an immune checkpoint inhibitor following disease progression after previous treatment with immunotherapy,” observes Cristina Suarez, Medical Oncologist at the Vall d’Hebron University Hospital (HUVH), Vall d’Hebron Barcelona Hospital Campus.

This study included 522 patients who were randomly assigned (1:1) to receive the combination of atezolizumab plus cabozantinib or cabozantinib monotherapy. Presented today at the 2023 Annual Meeting of the American Society of Clinical Oncology (ASCO) (1), 2-6 June (Chicago, IL), data showed no difference in progression-free survival or overall survival which were co-primary endpoints in the trial. Furthermore, no difference in response rate was observed, and there was a notable increase in toxicity with the addition of atezolizumab. These results published in parallel in The Lancet (2) .

“Our findings should discourage the sequential use of immune checkpoint inhibitors in renal cell carcinoma outside of clinical trials. They also highlight the importance of prospective assessment of immunotherapy rechallenge across tumor types,” concludes Suarez.

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References:

  1. Toni K. Choueiri, Laurence Albiges, Piotr Tomczak, Cristina Suárez, Martin H Voss, Guillermo de Velasco, Jad Chahoud, Giuseppe Procopio, Hakim Mahammedi, Friedemann Zengerling, Chan Kim, Suyasha Gupta, Guillaume Bergthold, Bo Liu, Melania Kalaitzidou, Mahrukh A. Huseni, Christian Scheffold, Thomas Powles, Sumanta Kumar Pal. Efficacy and safety of atezolizumab plus cabozantinib vs cabozantinib alone after progression with prior immune checkpoint inhibitor (ICI) treatment in metastatic renal cell carcinoma (RCC): Primary PFS analysis from the phase 3, randomized, open-label CONTACT-03 study.


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