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Abstract
Background The correlation between initial tumor burden (TB) and immunotherapy outcomes is not known. We used a unique data resource consisting of a federally (NCI) funded basket trial (NCT02834013) for patients with rare cancers to evaluate associations between baseline TB as documented by standardized radiographic response criteria and outcomes after therapy with nivolumab combined with ipilimumab.
Methods Baseline TB was assessed by the sum of the longest diameters (RECIST v1.1 target lesions) from the pre-treatment scan. Overall survival (OS) and progression-free survival (PFS) were measured from study registration date. Descriptive visual evaluation using Martingale residual and cubic spline plots indicated non-linear associations. To capture potential non-linear association, quartiles of TB were analyzed using univariate and multivariable (controlling for age, performance status [PS], sex, and ethnicity) Cox regression models, which were stratified by basket to account for varying baseline hazards. Fisher’s exact and Wilcoxon rank sum tests were used to evaluate covariate associations with baseline TB.
Results The trial was conducted by the SWOG Early Therapeutics and Rare Cancers Committee and was open at >1000 sites. Patients (N=722) from 52 rare cancer baskets were evaluable. Median age was 60 years. The TB quartiles for this cohort were 1–4.7, 4.8–8.0, 8.1–12.8, and 12.9+cm. Increasing baseline TB was associated with younger age (median 63, 60, 60, 58 years, respectively, p=0.018) and increasing rates of performance status 2 vs 0 or 1 (4%, 5%, 5%, 11%, respectively, p=0.031). The largest versus smallest quartile correlated with shorter PFS (table 1, p=0.030), but lost significance on multivariable adjustment (p=0.071). The 2 largest quartiles were associated with significantly shorter OS compared to the smallest quartile on both univariate (table 1, p=0.022 and <0.001) and multivariable analysis (table 1, p=0.021, p<0.001).
Conclusions In this large cohort of patients with rare tumors receiving checkpoint inhibitors, smaller baseline TB was predictive for longer survival after immunotherapy.
Acknowledgements NIH/NCI grants CA180888 and CA180819 and in part by Bristol-Myers Squibb Company.
Trial Registration NCT02834013.
Ethics Approval S1609 (NCT02834013) was approved by the ethics review committee at each institution/practice where the study was open.
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