Abstract 4406: Impact of site of metastases on response to immunotherapy in microsatellite stable (MSS) metastatic colorectal cancer (mCRC)
Authors: Fakih Marwan , Sandhu Jaideep , Li Xiaochen , Wang Chongkai 
Published: April 2023

Abstract
Background: We have noted that responses to the combinations of regorafenib and nivolumab (REGONIVO) or regorafenib ipilimumab nivolumab (RIN) were limited to MSS mCRC without liver involvement. We sought to delineate the impact of non-liver metastatic sites on the response to these combinations.
Methods: We performed a single center retrospective analysis of MSS mCRC receiving REGONIVO or RIN. To isolate the impact of immunotherapy on metastatic disease sites, we performed a 2-month (mo) analysis of organ specific response using organ specific RECIST assessment.
Results: 96 patients (Pts) (39 RIN and 57 REGONIVO) were evaluated. Overall response rate (ORR), median progression free survival (PFS), and median overall survival (OS) were 0%, 2 mo, and 7 mo in pts with liver metastatic (LM) disease (n = 33). We focused on the impact of other metastatic disease site on OS and PFS within the non-LM group to exclude liver as a confounding variable (n=63). Pts with lung-only mCRC had the best prognosis with an ORR, median PFS, and median OS of 56%, 13 mo, and unreached at 24 mo. Pts with peritoneal mCRC fared poorly (ORR 0%, median PFS= 1.5 mo, median OS =12 mo). A high ORR (75%) was noted in a small cohort of 4 pts with lymph node only disease. However, concurrent LN with lung only mCRC diminished efficacy outcomes. Differences in PFS and OS by organ involvement were independent of treatment (REGONIVO or RIN) based on estimates from Cox proportional hazard model. 2-mo response rates by metastatic sites are shown in Table 1. Responses at the 2-mo mark in the 96 pt cohort occurred in lung, LN, and soft tissue metastases but were most robust in lung only metastatic disease.
Conclusions: Responses to the combination REGONIVO or RIN are most robust in lung-only metastatic disease and appear to be modest in the setting of LN and soft tissue involvement. Liver and peritoneal disease was associated with lack of benefit from these combinations.
Table 1. 2-month Response Rates by Site of Metastatic Disease Sites of mCRC Number of Pts PD SD PR+CR Lung 72 33 (45.8%) 21 (29.2%) 18 (25.0%) Lung response in the setting of liver mets 27 18 (66.7%) 7 (25.9%) 2 (7.4%) Lung response without liver mets 45 15 (33.3%) 14 (31.1%) 16 (35.6%) Lung response in lung only metastatic disease 16 3 (18.8%) 4 (25.0%) 9 (56.2) Liver 33 31 (93.9%) 2 (6.1%) 0 (0%) Lymph Node (LN) 49 32 (65.3%) 12 (24.5%) 5 (10.2%) LN in the setting of liver mets 22 20 (90.9%) 2 (9.1%) 0 (0%) LN in the setting of no liver 30 14 (46.7%) 11 (36.7%) 5 (16.6%) LN only 4 1 (25%) 0 (0%) 3 (75%) Peritoneal 15 14 (93.3%) 1 (6.7%) 0 (0%) Soft tissue 30 11 (39.3%) 15 (53.6%) 2 (7.1%) Bone 8 4 (50%) 4 (50%) 0 (0%) Brain 1 1 (100%) 0 (0%) 0 (0%) Spleen + Adrenal 5 4 (80%) 1 (20%) 0 (0%)
Citation Format: Marwan Fakih, Jaideep Sandhu, Xiaochen Li, Chongkai Wang. Impact of site of metastases on response to immunotherapy in microsatellite stable (MSS) metastatic colorectal cancer (mCRC). [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4406.