Immunotherapy can be associated with prolonged disease control even after cessation of treatment without the need for further cancer-directed therapy. Treatment-related adverse events (TRAEs) can also persist after discontinuation of therapy.
Treatment-free survival (TFS) with and without toxicity as a component of a partitioned survival model can characterize patient survival time, which is not captured by standard outcome measures.
Data from 1096 patients with advanced renal cell carcinoma treated with first-line nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib (SUN) in the CheckMate 214 trial were analyzed. TFS was defined as the area between two Kaplan-Meier curves for time from randomization to protocol therapy discontinuation and time from randomization to subsequent systemic therapy initiation or death, estimated as the difference in 60-month restricted mean times with confidence intervals (CIs) obtained using bootstrap sampling. Time on protocol therapy and TFS were further characterized as time with and without grade 2+ and 3+TRAEs. Survival functions were estimated in subgroups including International Metastatic Renal Cell Carcinoma Database Consortium risk groups using the Kaplan-Meier method.
At 5 years from randomization, 48% of patients treated with NIVO+IPI and 37% of patients treated with SUN were alive. In the intent-to-treat population, 18% of the NIVO+IPI-treated and 5% of SUN-treated patients are surviving treatment-free. For favorable-risk patients, the 60-month mean TFS was 14.4 months for NIVO+IPI versus 5.5 months for SUN (difference 8.9 months (95% CI 4.9 to 12.8)). TFS for NIVO+IPI versus SUN with grade 2+TRAEs was 5.0 and 2.1 months, respectively, and with grade 3+TRAEs was 1.2 and 0.3 months, respectively. For intermediate/poor-risk patients, the 60-month mean TFS was 10.1 months for NIVO+IPI versus 4.1 months for SUN (difference 6.1 months (95% CI 4.2 to 7.9)). TFS for NIVO+IPI versus SUN with grade 2+TRAEs was 4.0 versus 2.0 months, respectively, and 0.6 versus 0.3 months with grade 3+TRAEs.
Although overall survival was similar, favorable-risk patients treated with NIVO+IPI spent more time surviving treatment-free with and without toxicity versus SUN after 60 months of follow-up. Intermediate/poor-risk patients treated with NIVO+IPI had longer survival and longer TFS without toxicity versus SUN.
NCT02231749.
Journal for immunotherapy of cancer. 2024 Jul 25*** epublish ***
Charlene M Mantia, Opeyemi A Jegede, Elizabeth R Plimack, Thomas Powles, Robert J Motzer, Nizar M Tannir, Chung-Han Lee, Yoshihiko Tomita, Martin H Voss, Toni K Choueiri, Brian I Rini, Hans J Hammers, Bernard Escudier, Laurence Albigès, Lisa Rosenblatt, Michael B Atkins, Meredith M Regan, David F McDermott
Harvard Medical School, Boston, Massachussetts, USA., Division of Biostatistics, Dana-Farber Cancer Institute, Boston, Massachusetts, USA., Department of Hematology/Oncology, Fox Chase Cancer Center, Temple Health, Philadelphia, Pennsylvania, USA., Department of Urology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free National Health Service Trust, London, UK., Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Department of Urology, Department of Molecular Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan., Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA., Division of Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, USA., Department of Medical Oncology, Gustave Roussy, Villejuif, France., Department of Cancer Medicine, Gustave Roussy, Villejuif, France., Bristol Myers Squibb, Princeton, New Jersey, USA., Georgetown-Lombardi Comprehensive Cancer Center, Washington, District of Columbia, USA., Harvard Medical School, Boston, Massachussetts, USA .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/39060019