The 2022 ASCO annual meeting featured a session on kidney and bladder cancer, including a presentation by Dr. Lucia Carril-Ajuria discussing the prognostic value of the lung immune prognostic index in patients with untreated advanced RCC receiving nivolumab + ipilimumab or sunitinib in the CheckMate 214 trial.1 The lung immune prognostic index, defined by lactate dehydrogenase (LDH) and derived neutrophil to lymphocyte ratio, has been shown to correlate with outcomes of immune checkpoint inhibitor therapy in patients with lung and other cancers, including patients with previously treated advanced RCC receiving nivolumab in the phase 2 NIVOREN GETUG-AFU 26 trial. At ASCO 2022, Dr. Carril-Ajuria reports an analysis of lung immune prognostic index in patients with previously untreated advanced RCC receiving nivolumab + ipilimumab or sunitinib in the randomized phase 3 CheckMate 214 trial with a minimum of 5 years of follow-up.2
Data were used from CheckMate 214 comparing nivolumab + ipilimumab (nivolumab 3 mg/kg + ipilimumab 1 mg/kg) vs sunitinib (50 mg) for untreated advanced RCC (n = 1,096). Patients with available lung immune prognostic index data were categorized into 3 lung immune prognostic index groups:
- Good [LG]: derived neutrophil to lymphocyte ratio ≤ 3 and LDH ≤ upper limit of normal [ULN])
- Intermediate [LI]: derived neutrophil to lymphocyte ratio > 3 or LDH > ULN
- Poor [LP]: derived neutrophil to lymphocyte ratio > 3 and LDH > ULN)
This analysis focused on the prognostic value of lung immune prognostic index using overall survival (OS) outcomes. Univariable analyses were conducted to evaluate lung immune prognostic index groups alongside known risk factors including age, sex, IMDC risk, baseline PD-L1 status, prior nephrectomy, and baseline tumor burden. Variables that were statistically significant in univariable analyses (p < 0.1) were included in the full multivariable analyses, from which a reduced model was generated.
A total of 1,084 patients were evaluable for lung immune prognostic index (nivolumab + ipilimumab, n = 542; sunitinib, n = 542). Patients were distributed evenly between treatment arms for all 3 lung immune prognostic index groups, but distribution between lung immune prognostic index groups was unbalanced, with most patients grouped as LG:
OS outcomes were improved with nivolumab + ipilimumab over sunitinib across all lung immune prognostic index groups. Moreover, patients in the LG group had better OS outcomes vs patients in the LI or LP groups regardless of treatment (nivolumab + ipilimumab: LG vs LI/LP HR 0.68, 95% CI 0.52-0.88), but with more distinct differences between lung immune prognostic index groups in the sunitinib arm (sunitinib: LG vs LI/LP HR 0.45, 95% CI 0.35-0.58):
Final multivariable analyses results showed the lung immune prognostic index correlated with OS for LI vs LG in the nivolumab + ipilimumab arm and for LI vs LG and LP vs LG in the sunitinib arm. PFS and duration of response by lung immune prognostic index group are as follows:
Dr. Carril-Ajuria concluded this presentation discussing the prognostic value of the lung immune prognostic index in patients with untreated advanced RCC receiving nivolumab + ipilimumab or sunitinib in the CheckMate 214 trial with the following take-home messages:
- These results indicate the potential prognostic value of the lung immune prognostic index in patients with untreated advanced RCC receiving nivolumab + ipilimumab or sunitinib
- The lung immune prognostic index appeared to have relatively weak predictive value with efficacy outcomes generally improved with nivolumab + ipilimumab versus sunitinib in both lung immune prognostic index groups
- Additional analyses are ongoing to further investigate the prognostic value of lung immune prognostic index in this patient population and its impact on other clinical outcomes
Presented by: Lucia Carril-Ajuria, MD, Gustave Roussy, Villejuif, France
Co-Authors: Robert J. Motzer, Nizar M. Tannir, David F. McDermott, Hans J. Hammers, Elizabeth R. Plimack, Frede Donskov, Brian I. Rini, Ruiyun Jiang, Chung-Wei Lee, Heshani Desilva, Laurence Albiges
Affiliations: Memorial Sloan Kettering Cancer Center, New York, NY, University of Texas MD Anderson Cancer Center, Houston, TX, Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, MA, UT Southwestern Kidney Cancer Program, Dallas, TX, Fox Chase Cancer Center, Philadelphia, PA, Aarhus University Hospital, Aarhus, Denmark, Vanderbilt-Ingram Cancer Center, Nashville, TN, Bristol Myers Squibb, Princeton, NJ
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 3 – Mon, June 7, 2022.
References:
- Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carinoma. N Engl J Med 2018;378(14):1277-1290.
- Albiges L, Tannir NM, Burotto M, et al. Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: Extended 4-year follow-up of the phase III CheckMate 214 trial. ESMO Open 2020 Nov;5(6):e001079.