In a study presented at the ASCO20 Virtual Scientific Program (Abstract 5077) and published as a brief report in JAMA Oncology, Ravi et al found that rechallenge with immune checkpoint inhibitor therapy was capable of producing responses in patients with metastatic renal cell carcinoma, including patients whose disease did not respond to initial immune checkpoint inhibitor therapy.
“The findings of this multicenter cohort study suggest that immune checkpoint inhibitor rechallenge in patients with metastatic renal cell carcinoma may be safe and reasonably efficacious, with an overall response rate of 23%.”— Ravi et al
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Study Details
The retrospective cohort study included 69 consecutive patients with metastatic renal cell carcinoma from nine U.S. institutions who received at least two separate lines of immune checkpoint inhibitor therapy alone or in combination with other therapies between January 2012 and December 2019. Immune checkpoint inhibitors included anti–cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), anti–programmed cell death protein 1 (PD-1), and anti–programmed cell death ligand 1 (PD-L1) therapies.
Median age at diagnosis of metastatic renal cell carcinoma was 61 years (range = 36–86 years); 50 (75%) of patients were male; and 60 (87%) had clear cell histology. Response was assessed according to Response Evaluation Criteria in Solid Tumors, version 1.1.
Treatment and Responses
At first-line treatment, treatments were immune checkpoint inhibition plus targeted therapy in 29 patients (42%), single-agent immune checkpoint inhibitors in 27 (39%), dual immune checkpoint inhibitors in 9 (13%), immune checkpoint inhibition plus chemotherapy in 2 (3%), and immune checkpoint inhibition plus an investigational agent in 2 (3%). Among 68 patients evaluable for response, 25 (37%) had partial response (no complete responses), 29 (43%) had stable disease, and 14 (21%) had progressive disease. Reasons for discontinuation of immune checkpoint inhibitor treatment were disease progression in 50 (72%), toxicity in 16 (23%), and other in 3 (4%).
At second-line treatment, treatments were single-agent immune checkpoint inhibitors in 26 (38%), dual immune checkpoint inhibitors in 22 (32%), immune checkpoint inhibition plus targeted therapy in 13 (19%), immune checkpoint inhibition plus chemotherapy in 1 (1%), and immune checkpoint inhibition plus an investigational agent in 7 (10%). Among 64 patients evaluable for response, partial response (no complete responses) was observed in 15 (23%), stable disease in 26 (41%), and progressive disease in 23 (36%).
Median time to progression was 8.2 months with first-line therapy vs 5.7 months with second-line therapy (P = .045).
Response with second-line therapy was observed in 7 (29%) of 24 patients with response to first-line therapy and in 3 (21%) of 14 patients with best response of progressive disease with first-line therapy. Response was observed in 7 (30%) of 23 patients receiving single-agent immune checkpoint inhibition at second-line therapy and in 3 (23%) of 13 receiving an immune checkpoint inhibitor plus targeted therapy. Among six evaluable patients receiving combined PD-1 and CTLA-4 inhibition as second-line therapy, response was observed in one patient (17%) who had received single-agent PD-L1 inhibition as first-line therapy.
Immune-Related Adverse Events
Immune-related adverse events of any grade occurred in 71% of patients with first-line therapy and 45% with second-line therapy. Grade ≥ 3 immune-related adverse events were observed in 18 patients (26%) undergoing first-line therapy, with the most common being elevated liver enzymes (9%), elevated amylase/lipase (6%), and pneumonitis (4%). Grade ≥ 3 events were observed in 11 patients (16%) undergoing second-line therapy, with the most common being elevated amylase/lipase (4%) and arthritis (3%). The risk of immune-related events with second-line therapy was higher in patients with such an event with first-line therapy (n = 20, 41%) vs those without such an event (n = 4, 20%). No treatment-related deaths were reported.
The investigators concluded, “The findings of this multicenter cohort study suggest that immune checkpoint inhibitor rechallenge in patients with metastatic renal cell carcinoma may be safe and reasonably efficacious, with an overall response rate of 23%. Data from prospective studies are needed to validate these findings and determine the role of sequential immune checkpoint inhibitor regimens in treatment of metastatic renal cell carcinoma.”
Toni K. Choueiri, MD, of Dana-Farber Cancer Institute, is the corresponding author for the JAMA Oncology article.
