Abstract 3493
Background
A goal of adjuvant therapy is to prolong disease-free survival, with the risk of mortality approaching that of the general population. From the literature, recurrences in stage III melanoma are most likely to occur within 3 years after surgery. Mixture-cure models (MCMs) capture survival heterogeneity of cancer patients by assuming they are either “cured” or “uncured”, where cured patients are defined as having a low risk of relapse.
Methods
We applied MCMs to 3-year recurrence-free survival (RFS) outcomes in patients with resected melanoma treated with adjuvant nivolumab (NIVO) or ipilimumab (IPI) in the double-blind, phase III CheckMate 238 trial (NCT02388906) and assumed that the cured fraction has mortality risks similar to that of the general population. Patient age, sex, and geographic region information from CheckMate 238 and mortality rates from the World Health Organization were used to derive a cohort-level background survival distribution representative of “cured” or “disease-free” patients. Parametric functions were used to model uncured population outcomes. Parameters of the MCM were estimated by means of maximum likelihood methods. Statistical goodness-of-fit metrics and visual inspection showed that generalized gamma and log-logistic distributions were best suited for survival analyses of cured and uncured patients, respectively.
Results
The 3-year RFS rates were explained by the fraction of patients with a low risk of relapse in the NIVO arm at 55.1% (95% CI, 49.2–60.1) and IPI arm at 39.9% (95% CI, 33.6–46.1). Sensitivity analyses indicated that the estimated fraction of patients with a low risk of relapse was > 50% in the NIVO arm. Estimated RFS distributions of the uncured patients exhibited similar patterns for both arms, implying the differences in RFS rates between treatment arms can be explained with the elicited differences in proportions of patients at high vs low risk of relapse.
Conclusions
MCM analyses from CheckMate 238 suggested that adjuvant treatment with NIVO leads to a higher proportion of patients with low risk of relapse compared with IPI. Validation of the results from MCMs will include analyses of longitudinal RFS and overall survival data from the EORTC 18071 trial.
Clinical trial identification
NCT02388906.
Editorial acknowledgement
Kakoli Parai, PhD, and Andrea Lockett at StemScientific, an Ashfield Company, funded by Bristol-Myers Squibb.
Legal entity responsible for the study
Bristol-Myers Squibb.
Funding
Bristol-Myers Squibb.
Disclosure
J.S. Weber: Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy, Shareholder / Stockholder / Stock options: AltorBioScience; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Research grant / Funding (institution): Astellas Pharma; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Licensing / Royalties, Named on a patent for a PD-1 antibody biomarker: Biodesix; Shareholder / Stockholder / Stock options: Biond; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: cCam Biotherapeutics; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Celldex; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Daiichi Sankyo; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: GlaxoSmithKline; Honoraria (self), Advisory / Consultancy: Ichor Medical Systems; Research grant / Funding (institution): Incyte; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Lion Biotechnologies; Honoraria (self), Advisory / Consultancy: Medivation; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Licensing / Royalties, Named on patent for an ipilimumab biomarker: Moffitt Cancer Center; Honoraria (self), Advisory / Consultancy: Nektar; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pieris Pharmaceuticals; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Sellas Life Sciences; Honoraria (self), Advisory / Consultancy: WindMIL; Honoraria (self), Advisory / Consultancy, Shareholder / Stockholder / Stock options: CytomX Therapeutics; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis. M. Kurt: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. M. Edmondson-Jones: Advisory / Consultancy: Bristol-Myers Squibb. A. Amadi: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. M. Lobo: Full / Part-time employment: Bristol-Myers Squibb. A. Moshyk: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. S. Kotapati: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. P. Mohr: Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy: GlaxoSmithKline; Honoraria (self), Advisory / Consultancy: Merck, Sharp & Dohme; Honoraria (self), Advisory / Consultancy: Merck Germany; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Sanofi.
Resources from the same session
1541 - TERT gene fusions characterize a subset of metastatic Leydig cell tumors
Presenter: Bozo Kruslin
Session: Poster Display session 3
Resources:
Abstract
5389 - Two-weekly accelerated BEP (aBEP) regimen as induction chemotherapy (CT) in intermediate and poor prognosis patients (pts) with nonseminomatous germ cell tumors (NSGCT): final results of phase II trial.
Presenter: Alexey Tryakin
Session: Poster Display session 3
Resources:
Abstract
2934 - Differential expression of circulating miR375 and miR371 to detect teratoma and viable germ cell malignancy
Presenter: Lucia Nappi
Session: Poster Display session 3
Resources:
Abstract
3585 - Prognosis of anaemia in disseminated testicular germ cell tumours. On behalf of the Spanish Germ Cell Cancer Group (SGCCG)
Presenter: Esmeralda Garcia Torralba
Session: Poster Display session 3
Resources:
Abstract
2254 - The Effects Of Primary Testicular Tumor Localization On Prognosis In Patients With Nonseminomatous Testis Cancer
Presenter: Birol Yildiz
Session: Poster Display session 3
Resources:
Abstract
4505 - Initial Results of a Phase II study of Nivolumab and Ipilimumab in Metastatic Adrenal Tumors.
Presenter: Matthew Campbell
Session: Poster Display session 3
Resources:
Abstract
3369 - NEMIO: a randomized phase II trial evaluating efficacy and safety of dose dense MVAC (ddMVAC) + durvalumab +/- tremelimumab as neoadjuvant treatment in patients with bladder muscle-invasive urothelial carcinoma
Presenter: Constance Thibault
Session: Poster Display session 3
Resources:
Abstract
2075 - KEYNOTE-866: Phase 3 Study of Perioperative Pembrolizumab (pembro) or Placebo (pbo) in Combination With Neoadjuvant Chemotherapy in Cisplatin (cis)-Eligible Patients (pts) With Muscle-Invasive Bladder Cancer (MIBC)
Presenter: Arlene Siefker-Radtke
Session: Poster Display session 3
Resources:
Abstract
4824 - KEYNOTE-905: A Phase 3 Study of Cystectomy Plus Perioperative Pembrolizumab Versus Cystectomy Alone in Cisplatin (cis)-Ineligible Patients (pts) With Muscle-Invasive Bladder Cancer (MIBC)
Presenter: Matthew Galsky
Session: Poster Display session 3
Resources:
Abstract
2253 - Phase 3 LEAP-011 trial: First-Line Pembrolizumab With Lenvatinib in Patients With Advanced Urothelial Carcinoma Ineligible to Receive Platinum-Based Chemotherapy
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract