Background
NRG/GOG Study 279 was a single-arm phase II trial evaluating concurrent cisplatin-gemcitabine with intensity-modulated radiation therapy (IMRT) as definitive non-surgical treatment for locally advanced squamous cell carcinoma of the vulva not amenable to surgery. It addressed a critical unmet need in a rare disease where high-dose cisplatin-based CRT is extrapolated from cervical and anal cancer evidence; gemcitabine was added as a radiation sensitizer to potentially improve organ-preservation rates without exenteration.
Interventions and follow up
Regimen: Cisplatin 40 mg/m² + gemcitabine 50 mg/m² IV weekly × 6 weeks concurrent with IMRT (64 Gy with concurrent boost)
Primary endpoint: Complete pathologic response (CPR)
Secondary endpoints: PFS, OS, adverse events
mFollow-up: 51 months
Primary endpoint: Complete pathologic response (CPR)
Secondary endpoints: PFS, OS, adverse events
mFollow-up: 51 months
Results
CPR: 38/52 patients (73%; 90% CI 61–83%)
12-mo PFS: 74% (90% CI 62.2–82.7%)
24-mo OS: 70% (90% CI 57–79%)
Surgery: no pelvic exenterations performed; one Grade 5 event assessed as unlikely treatment-related
12-mo PFS: 74% (90% CI 62.2–82.7%)
24-mo OS: 70% (90% CI 57–79%)
Surgery: no pelvic exenterations performed; one Grade 5 event assessed as unlikely treatment-related
Adverse events
Hematologic: most common Grade 3–4 — neutropenia and thrombocytopenia
Dermatologic: radiation dermatitis common
Discontinuation: 7 patients (12%) came off trial due to toxicity or patient withdrawal; Grade ≥3 GI toxicity uncommon; no unexpected long-term toxicity reported
Dermatologic: radiation dermatitis common
Discontinuation: 7 patients (12%) came off trial due to toxicity or patient withdrawal; Grade ≥3 GI toxicity uncommon; no unexpected long-term toxicity reported
Conclusions
Concurrent cisplatin-gemcitabine with IMRT achieved a 73% complete pathologic response rate and 74% 12-month PFS in locally advanced unresectable vulvar squamous cell carcinoma, demonstrating that organ preservation without pelvic exenteration is achievable and establishing this regimen as a viable definitive CRT approach for this rare disease.
Key Limitations
Single-arm, non-randomized design — no comparison to single-agent cisplatin CRT (historical standard); small sample size (n=52 evaluable) limits statistical precision; predominantly White patient population (94%) limits generalizability; 90% CI used (not 95%), consistent with phase II design; CPR as primary endpoint rather than PFS or OS; median age 58 years may not reflect elderly patients less fit for gemcitabine; pathologic response required post-CRT resection (not all patients resected — 7 discontinued); no biomarker selection (HPV status, PD-L1).
Clinical Context
Vulvar squamous cell carcinoma is rare (~6,000 cases/year in the US) with no FDA-approved systemic therapies and limited Level I evidence for definitive CRT. NRG/GOG 279 provides the highest-quality prospective evidence for cisplatin-gemcitabine IMRT in the locally advanced setting, improving on historical cisplatin-only CRT data. The 73% CPR rate compares favorably to single-agent cisplatin-CRT historical benchmarks (~50–65%). No pelvic exenterations in the response-evaluated cohort is a clinically meaningful organ-preservation result. ASCO and ESMO recognize concurrent cisplatin-based CRT for unresectable disease; NRG/GOG 279 supports gemcitabine addition as a sensitizer. There is ongoing interest in HPV-targeted immunotherapy (pembrolizumab) combinations in vulvar cancer.