Immune checkpoint inhibitor (ICI) retreatment in advanced melanoma is used in clinical practice, but there is a lack of evidence to support it, according to research presented at the NCCN 2023 Annual Conference.
“Although immune checkpoint inhibitors and targeted therapies revolutionized the treatment of advanced melanoma over the past few decades, the majority of patients experience disease progression after initial treatment, and options are limited in this setting. Checkpoint inhibitor retreatment is common, despite a lack of comparative evidence to support its use,” said study presenter Daniel Olson, MD, of the University of Chicago Comprehensive Cancer Center in Illinois.
To evaluate the current evidence supporting the use of ICI retreatment in the setting of advanced melanoma, Dr Olson and colleagues conducted a systematic review of the literature. The review included 8 studies — 6 retrospective analyses, 1 single-arm phase 2 trial, and 1 exploratory subgroup analysis.
The phase 2 trial included 70 patients who received pembrolizumab plus low-dose ipilimumab after progression on anti-PD-1 therapy. The response rate was 29%, the median duration of response was 16.6 months, and the median overall survival was 24.7 months.
In the exploratory subgroup analysis, 256 patients received ipilimumab or a BRAF inhibitor, with or without a MEK inhibitor, after progression on pembrolizumab. The response rate was 15.5% with ipilimumab, and the median overall survival was 9.8 months with ipilimumab.
The 6 retrospective analyses included a range of 57 patients to 335 patients. The retreatment regimens included ipilimumab alone, anti-PD-1 therapy alone, ipilimumab plus anti-PD-1 therapy, and ipilimumab plus nivolumab.
The response rates ranged from 8% to 33% for 5 studies, and the median overall survival ranged from 5.1 months to 21 months for 6 studies.
“[O]ur review found no prospective randomized trials that have studied use of checkpoint inhibitors after prior anti-PD-1 therapy,” Dr Olson said. “We found limited evidence of efficacy in highly selected and heterogeneous patient populations, mostly from retrospective studies that did not uniformly report response or define resistance to prior anti-PD-1 therapy.”
Dr Olson added that, after this review was conducted, data from the SWOG S1616 trial were published. Results from this phase 2 trial suggested that a minority of patients with advanced melanoma may benefit from ICI retreatment, and ipilimumab plus nivolumab provides a greater benefit than ipilimumab alone.
Similarly, a phase 3 study showed that ipilimumab can be somewhat effective in melanoma patients refractory to anti-PD-1 therapy, but tumor-infiltrating lymphocyte treatment appears more effective for these patients.
“Overall, I would say the comparison of outcomes across studies is challenging, and there is no robust, meaningful benchmark for novel therapies in this setting,” Dr Olson said. “Standardizing data collection and reporting on responses to prior treatment, appropriately indexing search strings as nomenclatures become more standardized, and defining the index date to measure outcomes will allow better comparison and synthesis of data across studies.”
Disclosures: This research was sponsored by Iovance Biotherapeutics, Inc. Study authors disclosed relationships with Iovance Biotherapeutics, Immunocore, Inhibrix, Instil Bio, Astellas, GLG Group, Alpha Insights, Castle Biosciences, Quest Imaging, Merck, Bristol Myers Squibb, Alkermes, NIT, and Regeneron.
Olson D, Gastman B, Rowell A, et al. Immune checkpoint inhibitor (ICI) treatment after progression on anti-PD-1 therapy in advanced melanoma: A systematic review of the literature. NCCN 2023. March 31-April 2, 2023. Abstract HSR23-110.