Background
Prospective Phase II study (Trans-Tasman Oncology Group) evaluating concurrent chemoradiation (CRT) for high-risk Merkel cell carcinoma. 53 patients with high-risk MCC (Stage III: lymph node involvement, T4 primary, or primary >1 cm). RT: 50 Gy + concurrent carboplatin and etoposide for 2 cycles. Assessed local control, regional control, and survival.
Interventions and follow up
Arm A: CRT: RT 50 Gy + concurrent carboplatin AUC2 day 1 + etoposide 100 mg/m² days 1–3, cycles 1 and 4 (of RT); single-arm Phase II
Arm B: N/A — single-arm desig
Primary endpoint: Locoregional control
mFollow up: 3 year
Arm B: N/A — single-arm desig
Primary endpoint: Locoregional control
mFollow up: 3 year
Results
3-Year Locoregional Control: 75%
3-Year OS: 71%
3-Year Distant Metastasis-Free Survival: 76%
Grade ≥3 toxicity: Myelosuppression 45%; manageable; no treatment-related deaths
3-Year OS: 71%
3-Year Distant Metastasis-Free Survival: 76%
Grade ≥3 toxicity: Myelosuppression 45%; manageable; no treatment-related deaths
Adverse events
Main adverse events: Grade ≥3 hematologic toxicity in 45% (myelosuppression from carboplatin/etoposide); mucositis in H&N sites; fatigue. Overall, chemotherapy added substantial acute toxicity. RT-related late effects consistent with field/dose.
Conclusions
Concurrent CRT achieves 75% 3-year locoregional control and 71% OS in high-risk MCC, with significant but manageable acute toxicity. Provides proof-of-concept that CRT is feasible and active in MCC, though its advantage over RT alone remains unproven in a randomized setting.
Key Limitations
Key Limitations: Single-arm Phase II; no randomized comparison with RT alone; selected high-risk population; carboplatin/etoposide regimen predates modern immunotherapy options; small sample; regional relapse and distant metastasis not fully separated in outcome reporting.
Clinical Context
The Poulsen Phase II study is the primary evidence for chemoradiation in high-risk MCC. However, as adjuvant chemotherapy shows no OS benefit (Bhatia NCDB 2016), RT alone is the standard adjuvant approach for resected MCC. CRT may be considered for unresectable or Stage III disease at specialized centers. Avelumab (anti-PD-L1) is now approved for metastatic MCC and is being studied in the adjuvant setting.
References