A multi-institutional retrospective analysis of immune checkpoint inhibitor efficacy in gynecologic cancers

Abstract

<h3>Objectives:</h3> Immune checkpoint inhibitor (ICI) therapy is the standard-of-care in several solid tumor malignancies, including gynecologic cancers (GYN). Several recent approvals are based on histology-agonistic trials where the relative efficacy in GYN cancers is lacking. Also, real-world efficacy data on ICI therapy in GYN malignancies are limited. The response rates to ICI rechallenge and the histologies most likely to respond are unknown. This study evaluates and characterizes clinical response to ICI therapy in GYN cancers. <h3>Methods:</h3> An IRB approved retrospective review was performed on adult women with gynecologic 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, disease characteristics, overall response rates (ORR), time to response, duration of response (DOR), and progression free survival (PFS). <h3>Results:</h3> Database review identified 129 eligible patients. The primary sites of disease were uterus (40%), vulvovaginal (22%), ovary (21%), and cervix (17%). Most patients received PD-1 inhibitor monotherapy (80.6%), 16.3% of patients received combination CTLA-4 and PD-1 inhibitor therapy. Monotherapy with anti-PD-L1 and anti-CTLA4 represented 2.3% and 0.8%, respectively. The ORR across all disease sites was 45%. The complete response rate, partial response rate, and stable disease rates were 24%, 62%, and 14%, respectively. The ORR in cervical cancer was 54.5%, 51.9% in uterine cancer, 35% in vulvar cancer, and 33.3% in ovarian cancer. The overall median time to response and DOR was 2.5 months and 4.5 months, respectively. Median DOR/PFS (months) were 10/13 (uterine), 3/5 (ovary) 3.8/7 (cervix), 5/7.8 (vulvar). Twenty-eight patients received a subsequent line of ICI therapy, and of these, 11 responded, including 3 patients (all with vulvar or cervical cancer) who had not responded to 1st line therapy. Eight patients experienced responses in both lines. The only 2 patients with ovarian cancer who responded to second-line ICI had a previous response (and subsequent progression) to first-line ICI. Of nine patients receiving third-line ICI treatment, there was only 1 response in a patient with vulvar melanoma. There were no responders to the fourth rechallenge with immunotherapy. <h3>Conclusions:</h3> Overall, 45% of patients responded to initial ICI therapy, with the majority experiencing a PR. Patients with uterine cancer benefited the longest from ICI therapy. Most patients who responded to second-line therapy were those who responded to initial therapy. All patients who responded to ICI rechallenge without an initial response had vulvar or cervical cancer. Patients with ovarian cancer who did not respond to initial ICI therapy were unlikely to respond to subsequent lines. The use and timing of ICI in GYN malignancies should consider primary site and patterns of prior response.