Abstract LBA50
Background
A post hoc analysis from the phase 3 CheckMate 816 study showed that residual viable tumor (RVT) in the primary tumor (PT) was associated with event-free survival (EFS) with N + C (2y EFS rates: 90%, 60%, 57%, and 39% in patients [pts] with 0–5, > 5–30, > 30–80, and > 80% RVT). Here, we report analyses in pts with or without (w/o) pathologic evidence of lymph node involvement (LN-I).
Methods
Adults with resectable NSCLC were randomized to receive N 360 mg + platinum-doublet C Q3W or C alone Q3W for 3 cycles, followed by resection. Primary endpoints were pathologic complete response (pCR) and EFS (both met). Analyses included efficacy by LN-I and assessment of prespecified histopathologic features (%RVT, regression, and necrosis) in PT and LN. Pts with LN-I could have had either 0% (pathologic evidence of completely regressed tumor) or > 0%RVT in the resected LN. A time-dependent ROC curve analysis assessed the predictive ability of %RVT in PT for 2y EFS.
Results
pCR rates were improved with N + C vs C in both pts with or w/o LN-I (table); similar EFS benefit was seen in pts with or w/o LN-I (HR: 0.69 and 0.74). In the N + C arm, pts with LN-I who had 0% RVT in both PT and LN showed the best EFS outcomes numerically, followed by those with 0% RVT in either PT or LN; those with > 0% RVT in both PT and LN showed shorter EFS (2y EFS rates: 92%, 76%, and 49%). Overall, lower %RVT and higher % regression (appears to be inversely related to RVT) was seen with N + C vs C in PT and LN; % necrosis did not differ between the treatment arms (table). In both pts with or w/o LN-I (N + C), %RVT in PT was predictive of EFS at 2y (AUC: 0.76 and 0.73).
Conclusions
These findings further support neoadjuvant N + C vs C as a novel treatment option for pts with resectable NSCLC, regardless of LN-I. %RVT in PT in pts with or w/o LN-I was associated with EFS with N + C. Further assessment of clinically relevant %RVT cutoffs to predict long-term outcomes with immunotherapy is warranted. Table: 000LBA50
| Path-evaluable a | ||||
| W/o LN-I | With LN-I | |||
| N + C (n = 72) | C (n = 51) | N + C (n = 68) | C (n = 74) | |
| Efficacy | ||||
| Median EFS (95% CI), mo | NR (30.6–NR) | NR (22.4–NR) | 31.6 (22.2–NR) | 22.7 (14.8–NR) |
| EFS HR (95% CI) | 0.74 (0.39–1.41) | 0.69 (0.42–1.13) | ||
| pCR, % 0% RVT, PT 0% RVT, LN 0% RVT, PT and LN 0% RVT, PT or LN | 40 – – – | 6 – – – | 24 34 19 38 | 3 5 1 7 |
| Path features, median (Q1–Q3) | ||||
| %RVT PT LN | 1 (0–48) – | 65 (12–90) – | 35 (2–82) 40 (0–100) | 82 (50–94) 96 (61–100) |
| % Regression PT LN | 80 (18–99) – | 20 (4–70) – | 40 (6–82) 20 (0–85) | 13 (4–44) 1 (0–15) |
| % Necrosis PT LN | 4 (0–18) – | 2 (0–10) – | 1 (0–16) 0 (0–15) | 1 (0–6) 0 (0–2) |
a140 (78%) and 125 (70%) of concurrently randomized pts in N + C and C arms had path-evaluable samples from both PT and LN. NR, not reached.
Clinical trial identification
NCT02998528.
Editorial acknowledgement
Editorial assistance in the writing of the abstract was provided by Wendy Sacks, PhD, and Michele Salernitano of Ashfield MedComms, an Inizio company.
Legal entity responsible for the study
Bristol Myers Squibb.
Funding
Bristol Myers Squibb.
Disclosure
J.S. Deutsch: Financial Interests, Personal, Other, Application No: 63/313,548: Patent pending. A. Cimino-Mathews: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Institutional, Funding, Research funding to institution: Bristol Myers Squibb. D. Wang: Financial Interests, Personal, Full or part-time Employment: Akoya Biosciences. P. Illei: Financial Interests, Personal, Advisory Board, Pathology advisory board on NSCLC biomarker testing: AstraZeneca, Bristol Myers Squibb, Janssen, Roche; Financial Interests, Personal, Invited Speaker, Unbranded education on NSCLC biomarker testing: Eli Lilly, Genentech; Financial Interests, Personal, Stocks/Shares, 100 SHARES: Bristol Myers Squibb; Non-Financial Interests, Institutional, Other, Co-PI on an institutional grant (central pathology review): Bristol Myers Squibb; Non-Financial Interests, Institutional, Other, Co-PI: Erbe GmBH. J. Spicer: Financial Interests, Personal, Other, speaker, consultancy, advisory role: Merck, BMS, Roche, AstraZeneca, Protalix Biotherapeutics, Chemocentryx; Financial Interests, Personal, Funding, Research funding: Merck, Roche, Protalix Biotherapeutics, CLS Therapeutics; Non-Financial Interests, Personal, Proprietary Information: AstraZeneca, Protalix Biotherapeutics, CLS Therapeutics. M. Provencio Pulla: Financial Interests, Personal, Advisory Board: BMS, MSD, Bayer, Lilly, Roche, Takeda, Janssen; Non-Financial Interests, Leadership Role, President of Spanish Lung cancer Group: President; Non-Financial Interests, Leadership Role, Insutituto Investigación Sanitaria Puerta de Hierro: Director. P.M. Forde: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, Daiichi, F-Star, G1, Genentech, Iteos, Janssen, Merck, Novartis, Sanofi, Surface; Financial Interests, Institutional, Funding, Research funding to institution: AstraZeneca, BioNTech, BMS, Corvus, Kyowa, Novartis, Regeneron ; Financial Interests, Personal, Other, Trial steering committee membership: AstraZeneca, Biontech, BMS, Corvus; Non-Financial Interests, Personal, Member of the Board of Directors: Mesothelioma Applied Research Foundation; Non-Financial Interests, Personal, Advisory Board: LUNGevity. D. Pandya: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. M.P. Tran: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. J. Fiore: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. V. Devas: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. J.M. Taube: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, AstraZeneca, Genentech, Akoya Biosciences, Lunaphore Technologies, Compugen; Financial Interests, Personal, Stocks/Shares: Akoya Biosciences; Financial Interests, Institutional, Funding, Research funding to institution: Bristol Myers Squibb, Akoya Biosciences; Non-Financial Interests, Personal, Other, Equipment loan and reagent provision: Akoya Biosciences; Other, Personal, Invited Speaker, Patent pending for machine learning for irPRC scoring: Akoya Biosciences. All other authors have declared no conflicts of interest.