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Objectives: Immune checkpoint inhibitors (ICI) are becoming standard of care in several advanced/recurrent gynecologic (GYN) malignancies. Yet, reported toxicities derive from basket and histology-specific clinical trials. Aggregate reports of real-world ICI toxicity, specifically in GYN cancers, are lacking. This study assesses and describes immune-related adverse events (irAE) in women receiving ICI. Methods: An IRB-approved retrospective review was performed on adult women with GYN malignancies treated with ICI, not under clinical trial, between January 2000 and June 2020 at the Mass General Brigham Integrated Health Care System and the Dana Farber Cancer Institute. Variables analyzed included patient demographics, ICI class, duration of therapy, time to first toxicity, subsequent toxicity with ICI retreatment, hospitalization rate, and therapy discontinuation. Toxicity was assessed by using CTCAE v5 criteria. Results: A total of 129 patients met inclusion criteria. The median age at the time of ICI treatment was 62 years. Fifty-two patients (40%) had uterine cancer, vulvar/vaginal; 28 (22%), ovarian; 27 (21%), and 22 (17%) had cervical cancer. Eighty percent of patients received anti-PD-1 monotherapy, 16.3% received combination anti-CTLA-4 and PD-1, 2.3% received anti-PD-L1 monotherapy, and 0.78% received anti-CTLA-4 monotherapy. Twenty-two percent of patients received a second line of ICI after responding or progressing on a previous ICI, and 7% received a third line of ICI. Overall, 55 patients (42.6%) experienced an irAE. The median time to first toxicity was 42 days. Of the 50 patients with assessable toxicity, 25 (50%) experienced grade 1 toxicity, 17 (34%) grade 2, 18 (36%) grade 3, and 2 (4%) grade 4. There were 15 (25%) hospitalizations, and there were no treatment-related deaths. Twenty-one patients (38%) experienced GI toxicity, including colitis and hepatitis. Thirteen patients (23.6%) developed a rash, and 16 (29%) patients had endocrine toxicity, predominantly hypothyroidism. Pneumonitis occurred in 5.5% of patients. In total, 109 patients (84.4%) discontinued ICI therapy. Only 18 patients (16.5%) discontinued due to toxicity, and 58 patients (53.2%) discontinued for progressive disease. On rechallenge, 32% of patients developed new or recurrent toxicity. Download : Download high-res image (85KB) Download : Download full-size image Conclusions: ICI therapy is well-tolerated in patients with GYN cancer. Less than half of our cohort experienced autoimmune-related side effects, and most of these toxicities were grade 1. A very small percentage of patients discontinue treatment for toxicity, and on rechallenge, most patients do not develop new or worsening toxicity. This information may help guide patient counseling when initiating ICI therapy or in the development of combination clinical trials involving ICI. |
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