KEY TAKEAWAYS
- A phase 3 CheckMate-816 study aimed to quantify the percent RVT in PT and LNs using irPRC criteria and to determine whether pathologic response is associated with EFS in neoadjuvant therapy for lung carcinoma.
- The correlation between the percent RVT in tumors and improved EFS suggests that pathologic response could be an emerging marker of survival.
A standardized evaluation system for residual tumor in primary tumor (PT) and lymph nodes (LNs) is crucial for survival predictions and neoadjuvant therapy benefits. An analysis of CheckMate-816 delved into residual viable tumor (RVT) percentage and its impact on event-free survival (EFS). This marked the initial use of such a comprehensive scoring system in a phase 3 trial.
In this phase 3 study, pathologic response was measured in patients with resectable non-small cell lung carcinoma receiving neoadjuvant nivolumab plus chemotherapy versus chemotherapy alone. RVT, regression, and necrosis percentages in PT and LNs were assessed using irPRC criteria (0%-100%). These pathologic features were examined for their association with EFS. Additionally, an exploratory analysis compared pathologic response, radiographic response, and ctDNA clearance.
Patients with 0% RVT in the primary site showed improved EFS regardless of LN involvement (HR=0.18). For nivolumab plus chemotherapy, RVT in the primary tumor predicted EFS (AUC=0.74). 2-year EFS rates varied: 90% (0%-5% RVT), 60% (>5%-30%), 57% (>30%-80%), and 39% (>80% RVT). A 1% increase in RVT was associated with a 0.017 HR increase for EFS.
Combining PT and LN responses differentiated outcomes. No increase in necrosis was seen in on-treatment samples in either arm. On-treatment necrosis correlated with lower EFS rates, challenging its role as a treatment effect indicator. Pathologic response closely mirrored EFS compared to radiographic response and ctDNA clearance.
Percent RVT links to enhanced EFS, suggesting its potential as a survival indicator. As %RVT holds prognostic value, its inclusion in standard pathology assessments could make it a biomarker guiding future adjuvant therapies. Additional exploration for clinically relevant %RVT thresholds in primary tumors and lymph nodes is necessary.
Source: https://jitc.bmj.com/content/11/Suppl_2/A1739
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT02998528
Deutsch JS, Cimino-Mathews A, Thompson E, et al222-N Analysis of pathologic features and efficacy outcomes with neoadjuvant nivolumab plus platinum-doublet chemotherapy for resectable non-small cell lung cancer in CheckMate 816Journal for ImmunoTherapy of Cancer 2023;11:doi: 10.1136/jitc-2023-SITC2023.0222-N
