• First results from the CheckMate 9ER phase III trial point to practice-changing data for the first-line treatment of patients with advanced clear-cell renal cancer, the most common kidney cancer in adults.
  • The combination of nivolumab, an anti-PD1 antibody, plus cabozantinib, a tyrosine kinase inhibitor, shows superior efficacy as first-line treatment in patients diagnosed with advanced or metastatic renal cell carcinoma.
  • This promising double punch approach met all efficacy endpoints versus sunitinib, the standard treatment for this tumor type at the time the trial started.

Barcelona, September 19, 2020.– Presented during The European Society for Medical Oncology’s (ESMO) Virtual Congress 2020, 19-21 September, during Presidential Session I* (Channel 1), first author Toni K. Choueiri, Dana-Farber Cancer Institute (Boston, USA), revealed the first results from the randomized phase III international CheckMate 9ER trial which explored the combination of a PD-1 immune checkpoint inhibitor antibody with a tyrosine kinase inhibitor -nivolumab plus cabozantinib- as first-line therapy of patients with advanced or metastatic clear-cell renal cancer, compared with sunitinib, the standard treatment for this disease up until the start of this present study.

Nivolumab and cabozantinib are approved therapies for the treatment of metastatic renal cell carcinoma (aRRC), and have shown improvements in overall survival (OS) as single agents in former phase III studies after treatment with TKIs. Providing the rationale for the CheckMate 9ER combination, nivolumab plus cabozantinib previously showed promising preliminary data in a phase I study in patients diagnosed with advanced genitourinary cancers**.

Enrolling a total of 651 patients with advanced or metastatic clear-cell renal cancer and who had not received any prior systemic therapy, the CheckMate 9ER Investigators compared the efficacy of the novel combination versus sunitinib. The main objective was to assess the variation in time to progression of the disease, which extended from 8.3 months with standard treatment to 16.6 months in the study arm combination, representing a 50% reduction in the risk of progression. Clinical benefit was also observed in secondary endpoints: a 40% decrease in the risk of death, and an improvement in the confirmed response rate to treatment, which increased from 27.1% in the standard treatment group to 55.7% with the novel combination.

Commenting for VHIO’s Global Communications, Cristina Suárez, Clinical Investigator of our Genitourinary Tumors Program, Medical Oncologist, Vall d’Hebron University Hospital (Vall d’Hebron Barcelona Hospital Campus), and co-author of CheckMate 9ER, noted, Importantly, 8% of the patients who received nivolumab plus cabozantinib showed a complete response, compared to 4.2% of those treated with sunitinib. This is particularly relevant in kidney cancer since previous investigations have shown that the magnitude of tumor response is related to its duration, and ultimately, patients’ survival.”

She continued, “The relevance of this study is that it points to a new first-line, more effective treatment avenue for these patients. Furthermore, it confirms the role of immunotherapy-based therapies against this tumor type which has been previously evidenced in three independent studies.”

This new therapeutic approach showed significant improvement in all endpoints, was generally well tolerated with a low rate of treatment-related discontinuations, and patients had an improved quality of life versus treatment with sunitinib. While 61% of those patients who received the novel combination had some type of moderate adverse event, compared to 51% observed in the patients who continued treatment with sunitinib, this is to be expected. A greater number of adverse events are observed when administering two drugs as opposed to only one. Importantly though, the increase was very small and secondary events were, in general, easily manageable.

 “Collectively, these first results support nivolumab plus cabozantinib as a potential, more potent first-line treatment option for patients with advanced renal cell carcinoma and thus, an important advancement towards improving outcomes for our patients,” concluded Cristina Suárez.

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References:

*The European Society for Medical Oncology’s (ESMO) Virtual Congress 2020 (19-21 September),
Presidential Session I, Channel 1:
696O_PR – Nivolumab + cabozantinib vs sunitinib in first-line treatment for advanced renal cell carcinoma: First results from the randomized phase III CheckMate 9ER trial.
Lecture Time: 19:34 – 19:46
Speaker: Toni K. Choueiri (Boston, USA)

**Nadal RM, et al. J Clin Oncol 2018;36(6 suppl):515.