Abstract 495P
Background
Microsatellite stable (MSS) metastatic colorectal cancer (mCRC) represent 95% of all mCRC cases and are characterized by resistance to PD-1 or PD-L1 checkpoint inhibition. Liver metastatic disease has been associated with decreased responses to immunotherapy in non-small cell lung cancer and melanoma. However, the impact of metastatic disease to the liver in MSS mCRC on treatment response has not been investigated in the setting of PD-1 or PD-L1 targeting.
Methods
Following IRB approval, we performed a retrospective study to assess the response rate (RR) and progression free survival (PFS) to PD-1 or PD-L1 based therapy in patients with MSS mCRC who progressed following standard chemotherapy and targeted therapy. Patients were included in the analysis if they received an FDA approved anti-PD1 or anti-PD-L1 agent, alone or in combination with other investigational agents. Exclusion criteria included concurrent cytotoxic therapy. RR and PFS were determined by RECIST guidelines.
Results
89 patients with refractory MSS mCRC satisfied the inclusion criteria and were evaluable for analysis. 51, 14, 13, and 11 received nivolumab, atezolizumab, pembrolizumab, and durvalumab, respectively. 40, 8, 10, 10, 17 received concurrent VEGFR, MEK, CTLA-4, radiation, or other targeted therapies. Patients were stratified into 4 groups: liver metastases (LM) at treatment (n = 51), no-liver metastasis (NLM) at treatment (n = 38), history of liver metastases (HLM) prior to or at treatment (n = 69), no history of liver metastases (NHLM) at any time prior to treatment (n = 20). NLM had superior PFS over LM (4 m vs. 1.5 m; HR = 0.41, p < 0.0001), NHLM had a superior PFS over HLM (4.3 m vs. 1.5 m; HR = 0.41, p <0.0001). PFS rates 4m/6 m were 0%/0% (LM), 55.3%/23.7% (NLM), 10.1%/1.5% (HLM), 70%/40% (NHLM). DCR/RR were 0%/0% (LM), 47.4%/10.5% (NLM), 11.6%/0% (HLM), 50%/20% (NHLM).
Conclusions
MSS mCRC patients with NLM and NHLM derive clinical benefits from checkpoint inhibitors while the presence of liver metastases appears to be prohibitive of benefit. PD-1/PD-L1 inhibitors should be re-investigated in prospective trials in MSS mCRC without LM.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M. Fakih: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Amgen; Advisory/Consultancy: Array; Advisory/Consultancy: Bayer; Advisory/Consultancy: Pfizer; Speaker Bureau/Expert testimony: Guardant360; Research grant/Funding (institution): Astra Zeneca; Research grant/Funding (institution): Novartis. All other authors have declared no conflicts of interest.