2760 - Should We Embrace INTERLACE?: Concurrent Pembrolizumab and Chemoradiotherapy for Locally-Advanced Cervical Cancer Requires More Invasive Brachytherapy Implants
Presenter(s)
G. K. Harada1, A. N. Munjal1, N. V. Peterson1, J. Park1, K. S. Hanubal1, A. Hari2, K. Clair2, J. Tseng2, R. Bristow2, K. Tewari2, J. V. Kuo1, P. Mitra3, and E. Healy1; 1Department of Radiation Oncology, University of California - Irvine, Orange, CA, 2Department of Gynecology Oncology, Chao Family Comprehensive Cancer Center, University of California, Irvine, Orange, CA, 3Department of Radiation Oncology, Chao Family Comprehensive Cancer Center, University of California, Irvine, Orange, CA
Purpose/Objective(s): The management of locally-advanced cervical cancer (LACC) has seen significant improvements with novel immunotherapy (KEYNOTE A18) and induction chemotherapy (INTERLACE) approaches. It is unclear which patients benefit most from a given approach and how these techniques may influence traditional external beam radiotherapy (EBRT) and brachytherapy (BT) practices. The purpose of this study was to assess KEYNOTE A18 and INTERLACE regimens on primary tumor response rate and associated BT approaches.
Materials/Methods: We performed a single institution retrospective review of all patients with a diagnosis of 2021 FIGO stage IB2 – IVA squamous cell carcinoma of the cervix between October 2023 to February 2025. All patients had bulky (=4 cm) disease treated with concurrent chemoradiotherapy and BT boost and were allowed to have induction chemotherapy with carboplatin and paclitaxel (INTERLACE) and/or concurrent immunotherapy with pembrolizumab (KEYNOTE A18). Patients were stratified by treatment regimen and assessed using T2-weighted MRI sequences of the pelvis at presentation and following EBRT to measure percent tumor volume decrease and extent of parametrial or vaginal disease. Secondary outcomes were assessed, and included incidence of interstitial BT, days missed for EBRT, and treatment toxicity. The threshold for statistical significance was set to p < 0.05.
Results: A total of 19 patients were identified with a median age of 45 years (IQR = 38–55 years). Most patients had FIGO stage IIIC1 disease (8/19 = 42.1%) and a median initial tumor size of 163.0 cc (IQR = 70.8–248.6 cc). Most patients were treated using chemoradiation with concurrent weekly cisplatin alone (8/19 = 42.1%), followed by 5 patients each receiving INTERLACE and KEYNOTE A18 regimens, respectively (5/19 = 26.3%). Median post-EBRT shrinkage was 95.8% for chemoradiation, followed by 100.0% for INTERLACE and KEYNOTE A18 (p = 0.106). Similarly, there were no differences in post-EBRT vaginal disease between regimens (p = 0.431). Patients receiving KEYNOTE A18 had significantly greater odds of post-EBRT parametrial disease (OR = 19.5, 95% CI = 1.30 – 292.75, p = 0.032) and required more interstitial BT than those receiving other regimens (OR = 24.0, 95% CI = 1.69 – 341.00, p = 0.019). There were no differences in number of days missed for EBRT (p = 0.700), or incidence of Grade 2 (p = 0.613) or Grade 3 (p = 0.907) toxicities between groups.
Conclusion: This is the first reported institutional experience assessing novel induction chemotherapy and concurrent immunotherapy approaches for LACC on primary tumor response. Patients treated with the KEYNOTE A18 regimen required more interstitial brachytherapy procedures after EBRT, possibly owing to poor response for parametrial disease, and suggests potential benefit of other paradigms in facilitating less-invasive intracavitary approaches. Future work is warranted in larger randomized settings to assess superiority of these regimens in the management of LACC.