Background and Objectives: Novel immunotherapy-based combination treatments have drastically improved clinical outcomes for previously untreated patients with advanced/metastatic renal cell carcinoma (aRCC). This study aimed to assess the temporal trends in grade 3/4 adverse event (AE) rates and associated costs of nivolumab plus cabozantinib combination therapy versus sunitinib monotherapy in previously untreated patients with aRCC. Methods: Individual patient data from the CheckMate 9ER trial (nivolumab plus cabozantinib: N = 320; sunitinib: N = 320) were used to calculate the proportion of patients experiencing grade 3/4 AEs. AE unit costs were obtained from the United States (US) 2017 Healthcare Cost and Utilization Project (HCUP) and inflated to 2020 US dollars. Per-patient-per-month (PPPM) all-cause and treatment-related grade 3/4 AE costs over 18-months, temporal trends, and top drivers of AE costs were evaluated in both treatment arms. Results: Overall, the proportion of patients experiencing grade 3/4 AEs decreased over time, with the highest rates observed in the first 3 months for the nivolumab plus cabozantinib and sunitinib arms. Compared with sunitinib, nivolumab plus cabozantinib was associated with consistently lower average all-cause AE costs PPPM [month 3: $2021 vs. $3097 (p < 0.05); month 6: $1653 vs. $2418 (p < 0.05); month 12: $1450 vs. $1935 (p > 0.05); month 18: $1337 vs. $1755 (p > 0.05)]. Over 18 months, metabolism and nutrition disorders ($244), laboratory abnormalities ($182), and general disorders and administration site conditions ($122) were the costliest all-cause PPPM AE categories in the nivolumab plus cabozantinib arm, and laboratory abnormalities ($443), blood and lymphatic system disorders ($254), and metabolism and nutrition disorders ($177) were the costliest in the sunitinib arm. Trends of treatment-related AE costs were consistent with all-cause AE costs. Conclusions: Nivolumab plus cabozantinib was associated with lower costs of grade 3/4 AE management PPPM than sunitinib, which accumulated over the 18-month study period.
Bibliographical noteFunding Information:
Analytical support was provided by Selvam R. Sendhil, BA, BS, and medical writing support was provided by Loraine Georgy, Ph.D., employees of Analysis Group, Inc.
Stephen Huo and Viviana Del Tejo are employees of Bristol Myers Squibb, which funded the development and conduct of this study and manuscript. Ella X. Du, Xiaoran Yang, and Keith A. Betts are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Bristol Myers Squibb. Daniel M. Geynisman received consulting fees from Pfizer, Exelixis, AstraZeneca, Seattle Genetics/Astellas, Eisai, Merck, Myovant Sciences, and 2nd.MD, as well as research funding from Genentech, Merck, Calithera Biosciences, Astellas Pharma, and Harpoon therapeutics. Mauricio Burotto received consulting fees from Roche/Genentech, Bristol Myers Squibb, MSD Oncology, Novartis, and AstraZeneca, as well as honoraria from Roche/Genentech, MSD Oncology, Bristol Myers Squibb, and AstraZeneca. Camillo Porta received consulting fees from Angelini Pharma, AstraZeneca, Bristol Myers Squibb, Eisai, EUSA Pharma, Ipsen, Merck Serono, and MSD, as well as honoraria from Bristol Myers Squibb, EUSA Pharma, General Electric, Ipsen, and MSD, payment for expert testimony from EUSA Pharma and Pfizer, and fees for attending meetings/travel from Roche. Cristina Suarez received research funding from AB Science, Aragon Pharmaceuticals, Astellas Pharma, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim España, Bristol Myers Squibb, Clovis Oncology, Exelixis, Genentech, GlaxoSmithKline, Hoffmann-La Roche, Novartis, Pfizer, and Sanofi-Aventis, as well as honoraria from Astellas Pharma, Bristol Myers Squibb, Hoffmann-La Roche, Ipsen, and Pfizer, and scientific advisory fees from Astellas Pharma, Bayer, Bristol Myers Squibb, EUSA Pharma, Hoffmann-La Roche, Ipsen, MSD, Novartis, Pfizer, and Sanofi-Aventis. Maria T. Bourlon received consulting fees from Bristol Myers Squibb, Asofarma, Eisai, MSD Oncology, Janssen Oncology, Novartis, Bayer, Ferring, as well as honoraria from Asofarma, MSD Oncology, Bristol Myers Squibb, Bayer, Eisai, Janssen Oncology, Ipsen, Pfizer, Merck, Ferring, Tecnofarma, Medicamenta, AstraZeneca, and Astellas Pharma, payment for expert testimony from Asofarma, support for attending meetings/travel from Asofarma, Janssen-Cilag, MSD Oncology, Bristol Myers Squibb Mexico, Pfizer, Ipsen, and Sanofi, and steering committee honoraria from Bristol Myers Squibb. Toni K. Choueiri participated in Data Safety Monitoring/Advisory Boards and received grants/contracts and consulting fees from AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers Squibb, Calithera, Circle Pharma, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, IQVIA, Infinity, Ipsen, Janssen, Kanaph, Lilly, Merck, Nikang, Nuscan, Novartis, Pfizer, Roche, Sanofi/Aventis, Surface Oncology, Takeda, Tempest, and UpToDate, and declares a leadership or fiduciary role in NCCN, GU Steering Committee, and ASCO/ESMO, owning stock or stock options in Pionyr, Tempest, Osel, and NuscanDx, institutional patents filed on molecular mutations and immunotherapy response, and ctDNA, medical writing and editorial assistance support which may have been funded in part by Communications companies, mentoring several non-US citizens on research projects with potential funding (in part) from non-US sources/Foreign Components, and receiving independent funding of drug companies or/and royalties potentially involved in research around the subject matter. Bradley McGregor received consulting fees from Exelixis, Bristol Myers Squibb, Pfizer, Seattle Genetics, Calithera, EMD Serono, Eisai, Asetellas, Dendreon, Nektar, and Bayer, as well as research funding from Exelixis, Bristol Myers Squibb, Pfizer, Seattle Genetics, and Calithera.
© 2022, The Author(s).