Key Message Highlights from Phase II Trial of Cisplatin, Gemcitabine, and Intensity-Modulated Radiation Therapy for Locally Advanced Vulvar Squamous Cell Carcinoma
Phase II Trial of Cisplatin, Gemcitabine, and Intensity-Modulated Radiation Therapy for Locally Advanced Vulvar Squamous Cell Carcinoma: NRG Oncology/GOG Study 279
Authors: Neil S. Horowitz, Wei Deng, Ivy Peterson, Robert S. Mannel, Spencer Thompson, Elizabeth Lokich, Tashanna Myers, Parvis Hanjani, David M. O’Malley, Ki Young Chung, David S. Miller, Frederick R. Ueland, Don S. Dizon, Austin Miller, Jyoti S. Mayadev, Charles A. Leath, Bradley J. Monk
Published in the Journal of Clinical Oncology on April 4, 2024
Introduction
Vulvar carcinoma is a rare gynecological cancer, often treated with extensive surgery resulting in significant morbidity. This NRG Oncology/GOG study aimed to assess the efficacy and toxicity of combining cisplatin, gemcitabine, and intensity-modulated radiation therapy (IMRT) for patients with locally advanced, unresectable vulvar squamous cell carcinoma.
Study Overview
- Objective: To determine the efficacy of adding gemcitabine to cisplatin and using IMRT rather than anteroposterior-posteroanterior (AP-PA) radiation, measured by the complete pathologic response (CPR) rate.
- Design: Single-arm, phase II trial that enrolled 57 patients.
- Treatment: Participants received 64 Gy of IMRT to the vulva and 50-64 Gy to the groins/low pelvis. Cisplatin (40 mg/m^2) and gemcitabine (50 mg/m^2) were administered weekly during radiation.
Key Findings:
- Complete Pathologic Response (CPR): Of the 52 evaluable patients, 38 (73%) achieved a CPR.
- Progression-Free Survival (PFS) and Overall Survival (OS): The 12-month PFS was 74% and the 24-month OS was 70%.
- Safety Profile: The most common grade 3 or 4 adverse events were hematologic toxicity and radiation dermatitis. There was one grade 5 event (sudden death) deemed unlikely related to treatment.
What We Learned:
- Combination Efficacy: The addition of gemcitabine to cisplatin and the use of IMRT significantly improved the CPR rate compared to historical results, with acceptable toxicity.
- Safety: The tolerable safety profile supports the feasibility of this chemoradiation regimen.
- Biomarker Importance: The impact of human papillomavirus (HPV) status on treatment response was not evaluated, which is an important consideration given the differences in outcomes between HPV-positive and HPV-negative vulvar cancers.
Key Takeaways:
- IMRT is appropriate for use in women with locally advanced vulvar carcinoma.
- The high CPR rate of 73% is particularly noteworthy, potentially reducing the need for debilitating pelvic exenterations.
- Limitations include the lack of diversity in the study population, with over 90% of participants being white.
- This study demonstrated the potential benefits of intensified chemoradiation strategies.
- Further research is warranted to confirm these findings, optimize patient selection, and explore the integration of emerging targeted and immunotherapeutic approaches.
Summary by Amalya Sargsyan