TARGET TRIAL EMULATION (TTE) INFORMED BY CLINICAL TRIAL DATA: ADJUVANT NIVOLUMAB VS OBSERVATION IN PATIENTS WITH RESECTABLE NON-SMALL CELL LUNG CANCER (RNSCLC) AFTER NEOADJUVANT NIVOLUMAB PLUS CHEMOTHERAPY AND SURGERY
Author(s)
Greta Lozano-Ortega, MSc1, Basia Rogula, MSc1, Stefano Lucherini, MSc2, Sumeena Bhatia, PhD3, Samantha Wilusz, PharmD3, Mariam Besada, MPH1, Lavanya Huria, MSc1, Eleanor Murray, ScD4.
1Broadstreet HEOR, Vancouver, BC, Canada, 2Bristol Myers Squibb, Uxbridge, United Kingdom, 3Bristol Myers Squibb, Princeton, NJ, USA, 4Independent Scholar, Boston, MA, USA.
1Broadstreet HEOR, Vancouver, BC, Canada, 2Bristol Myers Squibb, Uxbridge, United Kingdom, 3Bristol Myers Squibb, Princeton, NJ, USA, 4Independent Scholar, Boston, MA, USA.
Presentation Documents
OBJECTIVES: In CheckMate 816 (CM816), neoadjuvant nivolumab plus chemotherapy (neoNIVO+CT) significantly extended event-free (EFS) and overall survival compared with chemotherapy in patients with rNSCLC. CheckMate 77T (CM77T) followed a similar protocol but continued nivolumab after surgery (adjNIVO). However, the benefit of adjNIVO vs observation among patients treated with neoNIVO+CT and surgery has not been assessed head-to-head. We used individual-level patient data (IPD) to estimate the effect of initiating adjNIVO vs observation overall and within subgroups.
METHODS: A clone-censor-weight TTE was applied to estimate the effect on EFS of initiating adjNIVO within 160 days post-surgery. IPD were combined from the intervention arms of CM77T and CM816 (combined median follow-up: 40.9 months[SB1.1][BR1.2]; eligibility: patients who received 3-4 neoNIVO+CT doses and underwent surgery). Clones were censored at deviation from the assigned strategy or at adjuvant chemotherapy receipt. Stabilized inverse probability of censoring (IPC) weights were estimated in 5-day intervals. Baseline and time-varying confounders were considered. Hazard ratios (HRs) were estimated using IPC-weighted pooled logistic regression with restricted cubic splines for time. Variables for subgroup analyses included programmed death ligand 1 (PD-L1), major pathologic response (MPR), and pathologic complete response (pCR). 95% confidence intervals (CIs) were generated via bootstrapping.
RESULTS: Based on data from N=298 eligible patients, adjNIVO was associated with an EFS HR=0.89 (95% CI: 0.65, 1.22) vs observation. The largest observed adjNIVO benefit was in the PD-L1<1% subgroup (HR=0.60; 0.35, 0.87); a numerical benefit was estimated among patients who did not have MPR (HR=0.71; 0.46, 1.04) or pCR (HR=0.84; 0.58, 1.23).
CONCLUSIONS: Initiating adjNIVO after neoNIVO+CT and surgery may improve EFS among patients with rNSCLC including those with PD-L1<1% at baseline, or with no MPR or pCR[SB3.1]—populations with high unmet need. Small sample sizes and low event counts in key subgroups was a limitation. TTE provides a valuable causal inference framework for clinical trial data.
METHODS: A clone-censor-weight TTE was applied to estimate the effect on EFS of initiating adjNIVO within 160 days post-surgery. IPD were combined from the intervention arms of CM77T and CM816 (combined median follow-up: 40.9 months[SB1.1][BR1.2]; eligibility: patients who received 3-4 neoNIVO+CT doses and underwent surgery). Clones were censored at deviation from the assigned strategy or at adjuvant chemotherapy receipt. Stabilized inverse probability of censoring (IPC) weights were estimated in 5-day intervals. Baseline and time-varying confounders were considered. Hazard ratios (HRs) were estimated using IPC-weighted pooled logistic regression with restricted cubic splines for time. Variables for subgroup analyses included programmed death ligand 1 (PD-L1), major pathologic response (MPR), and pathologic complete response (pCR). 95% confidence intervals (CIs) were generated via bootstrapping.
RESULTS: Based on data from N=298 eligible patients, adjNIVO was associated with an EFS HR=0.89 (95% CI: 0.65, 1.22) vs observation. The largest observed adjNIVO benefit was in the PD-L1<1% subgroup (HR=0.60; 0.35, 0.87); a numerical benefit was estimated among patients who did not have MPR (HR=0.71; 0.46, 1.04) or pCR (HR=0.84; 0.58, 1.23).
CONCLUSIONS: Initiating adjNIVO after neoNIVO+CT and surgery may improve EFS among patients with rNSCLC including those with PD-L1<1% at baseline, or with no MPR or pCR[SB3.1]—populations with high unmet need. Small sample sizes and low event counts in key subgroups was a limitation. TTE provides a valuable causal inference framework for clinical trial data.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
MSR63
Topic
Methodological & Statistical Research
Disease
SDC: Oncology