- The phase III international CheckMate 9ER trial continues to make headlines. Now published ahead of print in The Lancet Oncology (1), extended follow-up of overall survival and updated efficacy and safety of PD-1 inhibitor nivolumab plus targeted therapy with cabozantinib point to a new standard of care for previously untreated patients with advanced renal cell cancer.
- Further confirming the efficacy of this double punch approach versus standard treatment with sunitinib, these data build on previous results of patient-reported outcomes where this combination significantly delayed time to deterioration of PROs compared to sunitinib (2).
- Most recently, results of exploratory analysis reported by VHIO’s Cristina Suárez at ASCO 2022 (3), showed that the depth of response to this novel combination associates with improved progression-free and overall survival in this patient population.
The phase III multi-center international CheckMate 9ER study was performed in 125 hospitals and cancer centers, including VHIO and the Vall d’Hebron University Hospital – HUVH (Vall d’Hebron Barcelona Hospital Campus), across 18 countries, and was designed to compare the efficacy of the novel combination of PD-1 inhibitor nivolumab plus targeted therapy with a tyrosine kinase inhibitor (TKI), cabozantinib, in patients with previously untreated advanced or metastatic clear-cell renal cancer (aRCC), the most common kidney cancer in adults.
Between September 2017 – May 2019 a total of 651 patients were enrolled in this trial; 323 patients were randomly assigned to receive the nivolumab-cabozantinib combination, and 328 patients were treated with sunitinib, the standard treatment for this disease up until the start of this study.
Nivolumab and cabozantinib are approved therapies for the treatment of aRCC, and previously showed improvements in overall survival as single agents in former phase III studies after treatment with TKIs. Providing the rationale for the CheckMate 9ER combination, nivolumab plus cabozantinib evidenced encouraging preliminary data in a phase I study (4) in patients with genitourinary cancers.
“In the primary analyses of CheckMate 9ER, this novel therapeutic pairing showed superior progression-free survival, overall survival, and objective response versus sunitinib in this patient population with a median follow-up of 18.1 months,” said Cristina Suárez, a Clinical Investigator of VHIO’s Genitourinary, CNS Tumors, Sarcoma & Cancer of Unknown Primary Site Group, and CheckMate 9ER Investigator. Results of subsequent analysis of patient-reported outcomes (PROs), showed that scores were either maintained or improved with this treatment pairing compared with sunitinib.
“This combination significantly delayed time to deterioration of PROs. Most recently, data from our exploratory research shows that patients receiving nivolumab plus cabozantinib achieved superior response rates versus sunitinib. In both arms, increasingly deeper responses led to improved overall survival,” added Cristina Suárez, a Senior Author of the exploratory analysis, who presented these data earlier this month at the American Society of Clinical Oncology (ASCO) Annual Meeting, 03 – 07 June 2022 (IL, USA).
Now published as an Article ahead of print in The Lancet Oncology (1), long-term follow up of CheckMate 9ER, first-authored by Robert J. Motzer, a Medical Oncologist and Head of the Kidney Cancer Section Head, Genitourinary Oncology Service at the Memorial Sloan Kettering Cancer Center (MSKCC), New York (NY, USA), assessed efficacy in all randomly assigned patients and evaluated safety in all patients who received at least one dose of any study drug.
With a median extended follow-up of 32.9 months, median overall survival was 37.7 months in the study arm combination compared with 34.3 months in the sunitinib group, and updated median progression-free survival extended from 8.3 months with standard treatment to 16.6 months with the novel combination, representing a 50% reduction in the risk of disease progression. While 65% of those patients who received the combinatorial therapy had treatment-related adverse events, compared to 54% observed in the patients who continued treatment with sunitinib, this is to be expected.
“As we previously reported, a greater number of adverse events were observed when administering two drugs as opposed to only one. Treatment-related events occurred in 65% of patients with nivolumab plus cabozantinib versus 54% in the sunitinib group. That said, in general, secondary events were easily manageable,” observed Cristina Suárez, a Medical Oncologist at the Vall d’Hebron University Hospital’s Medical Oncology Department, headed by VHIO’s Director, Josep Tabernero.
“Our extended follow-up and final overall survival analyses further support the combination of nivolumab plus cabozantinib in the first-line treatment of advanced renal cell carcinoma. Collectively, our data point to a paradigm shift in the treatment of this particular patient population,” concludes Cristina Suárez.
- Motzer RJ, Powles T, Burotto M, Escudier B, Bourlon MT, Shah AY, Suárez C, Hamzaj A, Porta C, Hocking CM, Kessler ER, Gurney H, Tomita Y, Bedke J, Zhang J, Simsek B, Scheffold C, Apolo AB, Choueiri TK. Nivolumab plus cabozantinib versus sunitinib in first-line treatment for advanced renal cell carcinoma (CheckMate 9ER): long-term follow-up results from an open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Jun 7:S1470-2045(22)00290-X. doi: 10.1016/S1470-2045(22)00290-X. Epub ahead of print.
- Cella D, Motzer RJ, Suarez C, Blum SI, Ejzykowicz F, Hamilton M, Wallace JF, Simsek B, Zhang J, Ivanescu C, Apolo AB, Choueiri TK. Patient-reported outcomes with first-line nivolumab plus cabozantinib versus sunitinib in patients with advanced renal cell carcinoma treated in CheckMate 9ER: an open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Feb;23(2):292-303.
- Abstract #4501. Cristina Suárez, Toni K. Choueiri, Mauricio Burotto, Thomas Powles, Maria T. Bourlon, Amishi Y. Shah, Yoshihiko Tomita, Jens Bedke, Joshua Zhang, Burcin Simsek, Christian Scheffold, Bernard Escudier, Robert J. Motzer, Andrea B. Apolo. Association between depth of response (DepOR) and clinical outcomes: Exploratory analysis in patients with previously untreated advanced renal cell carcinoma (aRCC) in CheckMate 9ER. J Clin Oncol, 40, 2022 (suppl 16; abstr 4501). https://meetinglibrary.asco.org/record/207895/abstract.
- Rosa Maria Nadal, Amir Mortazavi, Mark Stein, Sumanta K. Pal, Nicole N. Davarpanah, Howard L. Parnes, Yang-Min Ning, Lisa M. Cordes, Mohammadhadi H. Bagheri, Liza Lindenberg, Ryan Thompson, Seth M. Steinberg, Tina Moore, Tiffany Lancaster, Milisyaris Velez, Esther Mena, Rene Costello, Donald Bottaro, William L. Dahut, Andrea B. Apolo. Results of phase I plus expansion cohorts of cabozantinib (Cabo) plus nivolumab (Nivo) and CaboNivo plus ipilimumab (Ipi) in patients (pts) with with metastatic urothelial carcinoma (mUC) and other genitourinary (GU) malignancies. Clin. Oncol. 36, no. 6_suppl (February 20, 2018) 515-515.