In a study presented during the ASCO20 Virtual Scientific Program1 and published as a brief report in JAMA Oncology,2 Praful Ravi, MB, BChir, of the Dana-Farber Cancer Institute, Boston, and colleagues 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 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–CTLA-4, anti–PD-1, and anti–PD-L1 therapies.
"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%."— Praful Ravi, MB, BChir
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Median age at diagnosis of metastatic renal cell carcinoma was 61 years (range = 36–86 years); 50 patients (75%) were male; and 60 patients (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, immune checkpoint inhibitors plus targeted therapy were given to 29 patients (42%), single-agent immune checkpoint inhibitors were given to 27 (39%), dual immune checkpoint inhibitors wer given to 9 (13%), immune checkpoint inhibition plus chemotherapy was given to 2 (3%), and immune checkpoint inhibition plus an investigational agent was given to 2 (3%). Among 68 patients evaluable for response, 25 (37%) had a 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, single-agent immune checkpoint inhibitors were given to 26 (38%), dual immune checkpoint inhibitors were given to 22 (32%), immune checkpoint inhibition plus targeted therapy were given to 13 (19%), immune checkpoint inhibition plus an investigational agent were given to 7 (10%), and immune checkpoint inhibition plus chemotherapy were given to 1 (1%). Among 64 patients evaluable for response, a partial response (no complete responses) was observed in 15 (23%), stable disease in 26 (41%), and progressive disease in 23 (36%).
The median time to disease progression was 8.2 months with first-line therapy vs 5.7 months with second-line therapy (P = .045).
A response with second-line therapy was observed in 7 of 24 patients (29%) with response to first-line therapy in 3 of 14 patients (21%) with best response of progressive disease with first-line therapy. A response was observed in 7 of 23 patients (30%) receiving single-agent immune checkpoint inhibition at second-line therapy and in 3 of 13 (23%) receiving an immune checkpoint inhibitor plus targeted therapy. Among six evaluable patients receiving combined PD-1 and CTLA-4 inhibition as second-line therapy, a 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 were reported 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.”
1. Ravi P, Mantia C, Su C, et al: Use of immune checkpoint inhibitors (ICIs) after prior ICI in metastatic renal cell carcinoma: Results from a multicenter collaboration. ASCO20 Virtual Scientific Program. Abstract 5077.
2. Ravi P, Mantia C, Su C, et al: Evaluation of the safety and efficacy of immunotherapy rechallenge in patients with renal cell carcinoma. JAMA Oncol. May 29, 2020 (early release online).