205 PD-1/PD-L1/CTLA-4 inhibitor therapy following progression on a different PD-1/PD-L1 inhibitor: a case series

Background There are increasing numbers of immune checkpoint inhibitors (CPI) targeting the PD-1/PDL-1 and CTLA-4 pathways, which are approved in a wide variety of tumor types. A case series has previously described the sequential use of first line CPI, followed by second line CPI in renal cell carcinoma and melanoma patients, and both patient population had progressive disease. There is still a lack of data on the safety and efficacy of challenging a patient who has previously progressed on a CPI with a different class of CPI, in other tumor types. Methods We retrospectively collected data from patients treated with a CPI, who were subsequently challenged with another CPI, at a single institution. Exclusion criteria included patients with renal cell carcinoma and melanoma. Patient characteristics, immune-related adverse effects (irAEs), cancer type, tumor proportion score if available, treatment type, treatment response/progression per RECIST v1.1, and survival data were collected. Results We identified 11 patients with various pathologies who received sequential CPI after progressing on first line CPI (table 1). Cancer types included non-small cell lung cancer (n=5), head and neck cancer (n=2), urothelial carcinoma (n=1), Merkel cell carcinoma (n=1), poorly differentiated carcinoma (n=1), and hepatocellular carcinoma (n=1). The tumor proportion score was available in 6 patients. Out of these patients, all were metastatic at the time of second line CPI. First line CPIs were all PD(L)-1 inhibitors, second line CPIs were all PD(L)-1 inhibitors except for one patient who received a CTLA-4 inhibitor in combination with a PD-1 inhibitor. Out of these patients, 3 patients who were trialed with second line CPI had stable disease, 5 patients had progression of disease, 1 patient had an irAE leading to discontinuation of CPI, and 2 patients died from adverse events unrelated to CPI. Out of 3 patients with stable disease on second line CPI, 2 patients had stable disease for over 2 years, and 1 patient has had stable disease for over 1 year. Conclusions Despite concerns that sequential immunotherapy may not be efficacious, 3 out of 11 patients did significantly benefit with the long-term stable disease. We need further large-scale prospective studies and research to know more about tumor characteristics, the mechanism of resistance in immuno-oncology to help us identify patients who would benefit from sequential immunotherapy.