Nivolumab plus ipilimumab plus cabozantinib triplet combination for patients with previously untreated advanced renal cell carcinoma: Results from a discontinued arm of the phase III CheckMate 9ER trial Journal Article
| Authors: | Apolo, A. B.; Powles, T.; Escudier, B.; Burotto, M.; Zhang, J.; Simsek, B.; Scheffold, C.; Motzer, R. J.; Choueiri, T. K. |
| Article Title: | Nivolumab plus ipilimumab plus cabozantinib triplet combination for patients with previously untreated advanced renal cell carcinoma: Results from a discontinued arm of the phase III CheckMate 9ER trial |
| Abstract: | Background: The phase III CheckMate 9ER trial originally included a nivolumab plus ipilimumab plus cabozantinib triplet arm, which was discontinued early due to the evolving treatment landscape for first-line advanced renal cell carcinoma (aRCC). We report an exploratory analysis of patients randomised to the triplet regimen before enrolment discontinuation. Methods: Patients with clear-cell aRCC received nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg) Q3W for four cycles with once-daily cabozantinib (40 mg), then nivolumab (240 mg) Q2W plus once-daily cabozantinib (40 mg). CheckMate 9ER primary (progression-free survival [PFS] by blinded independent central review [BICR]) and key secondary (overall survival [OS], objective response rate [ORR] by BICR, and safety) endpoints were applied, along with investigator-assessed PFS and ORR. Results: Fifty patients were randomised to the triplet regimen. After a median follow-up of 39.1 months (range, 33.4–44.5), median PFS (95% CI) was 9.9 (5.7–16.8) months by BICR and 13.9 (7.3–24.7) months by investigator; median OS (95% CI) was 37.0 (31.8-not estimable) months. ORR (95% CI) was 44.0% (30.0–58.7; complete response, 8.0%) by BICR and 48.0% (33.7–62.6; all partial responses) by investigator. Grade 3–4 treatment-related adverse events (TRAEs) occurred in 84.0%, most commonly alanine aminotransferase increased (20.0%), aspartate aminotransferase increased (16.0%), and hepatotoxicity (16.0%). Grade 3–4 hepatic immune-mediated AEs occurred in 40.0%. There were no grade 5 TRAEs. Conclusions: These results suggest that the nivolumab plus ipilimumab plus cabozantinib triplet combination has clinical activity in patients with previously untreated aRCC, although monitoring of overlapping toxicities will be important in future studies of this regimen. ClinicalTrials.gov registration: NCT03141177. © 2022 |
| Keywords: | vasculotropin; adult; cancer survival; clinical article; controlled study; aged; middle aged; unclassified drug; overall survival; prednisone; clinical trial; fatigue; hepatitis; sunitinib; advanced cancer; cancer combination chemotherapy; diarrhea; drug safety; drug withdrawal; hypertension; side effect; cancer patient; follow up; ipilimumab; vasculotropin receptor; progression free survival; liver toxicity; multiple cycle treatment; anemia; mucosa inflammation; nausea; randomized controlled trial; stomatitis; myalgia; renal cell carcinoma; abdominal pain; arthralgia; asthenia; pneumonia; pruritus; rash; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; bilirubin; maculopapular rash; pazopanib; colitis; headache; phase 3 clinical trial; hyperthyroidism; hypothyroidism; axitinib; mammalian target of rapamycin inhibitor; hand foot syndrome; muscle spasm; protein ret; disease exacerbation; adverse drug reaction; treatment withdrawal; amylase; dysgeusia; triacylglycerol lipase; scatter factor receptor; programmed death 1 ligand 1; single blind procedure; adrenal insufficiency; decreased appetite; dysphonia; hypersensitivity; thyroiditis; cabozantinib; kit protein; body weight disorder; immune mediated injury; nivolumab; very elderly; objective response rate; human; male; female; article; treatment response time; axl protein |
| Journal Title: | European Journal of Cancer |
| Volume: | 177 |
| ISSN: | 0959-8049 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2022-12-01 |
| Start Page: | 63 |
| End Page: | 71 |
| Language: | English |
| DOI: | 10.1016/j.ejca.2022.09.020 |
| PROVIDER: | scopus |
| PUBMED: | 36327527 |
| PMCID: | PMC9750497 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 December 2022 -- Source: Scopus |
