Abstract 3844: Clinical implications of mixed response on prognosis of non-small cell lung cancer (NSCLC) patients treated with Immunotherapy

Abstract Background: Current methods for assessing the response of lung cancer patients to therapy (e. g. RECIST criteria) lack consideration for mixed response (MR) where some lesions increase while others decrease simultaneously. MR poses a challenge in deciding the continuation of therapy. Understanding the clinical implications of MR on patient prognosis within radiographic response categories is crucial for establishing effective treatment strategies for NSCLC. Methods: This study analyzed 177 NSCLC patients with ≥2 lesions receiving first-line systemic treatment with immunotherapy. Clinical response was evaluated by RECIST v1. 1 and immune-related RECIST (irRECIST). MR was defined as the simultaneous presence of ≥1 lesion increase and ≥1 lesion decrease during therapy. Two different definitions of MR were utilized. Definition-A (MR-A): the simultaneous presence of one or more lesions increasing ≥5mm and one or more lesions decreasing ≥5mm during therapy (Δ baseline - first follow-up ≥ 5 mm) ; and Definition-B (MR-B): the simultaneous presence of one or more lesions increasing 1mm and one or more lesions decreasing 1mm during therapy (any Δ baseline - first follow-up). Subgroup analysis was conducted using 94 patients with only intrathoracic lesions. Results: Among the 177 patients, tumor responses based on RECIST were 3 CR (1. 7%), 42 PR (23. 7%), 87 SD (49. 2%), and 45 PD (25. 4%). Based on irRECIST, responses were 3 CR (1. 7%), 46 PR (26. 0%), 89 SD (50. 3%), and 39 PD (22. 0%). MR-A and MR-B occurred in 19. 8% (n=35) and 45. 2% (n=80) of cases, respectively. In the irRECIST PD group, MR-A demonstrated significantly different median progression-free survival (mPFS) and median overall survival (mOS) compared to non-MR-A (p0. 020, p0. 005, respectively). The mPFS for MR-A group was 1. 4 months (range 0. 5-52. 9) and non-MR-A group was 5. 5 months (range 0. 2-97. 2) with the hazard ratio being 2. 91 (95% CI 1. 13-7. 51). The mOS for MR-A and non-MR-A groups were 4. 8 months (range 0. 7-61. 5) and 11. 8 months (range 0. 2-97. 2), respectively, hazard ratio 4. 87 (95% CI 1. 43-16. 56). No other significant results were found for other RECIST and irRECIST categories. Subgroup analysis of only intrathoracic lesion patients revealed no statistically significant results. Conclusion: Contrary to our hypothesis, MR did not modify prognosis within the RECIST or irRECIST category. MR-A or MR-B in the RECIST or irRECIST PD group did not show a better prognosis, indicating the complexity of mixed responses in NSCLC patients treated with immunotherapy. Further research with larger cohorts are warranted. Citation Format: Seyoung Lee, Taegyu Um, Jeeyeon Lee, Peter Haseok Kim, Monica Yadav, Maria J. Chuchuca, Liam Il-Young Chung, Young Kwang Chae. Clinical implications of mixed response on prognosis of non-small cell lung cancer (NSCLC) patients treated with Immunotherapy abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 3844.