Background
Phase 3 RCT (HOG LUN 01-24). 253 patients with unresectable stage III NSCLC who had NOT progressed after induction concurrent chemoRT (cisplatin-based + ≥59 Gy). Patients randomized at completion of CRT. Enrolled at Hoosier Oncology Group sites.
Interventions and follow up
Arm A: Pemetrexed 500 mg/m² IV q21 days × 4 cycles (consolidation chemotherapy)
Arm B: Observatio
Primary endpoint: OS
mFollow up: Median 25.7 month
Arm B: Observatio
Primary endpoint: OS
mFollow up: Median 25.7 month
Results
OS: 12.6 months (pemetrexed) vs 13.7 months (observation), HR 1.07 (95% CI 0.75–1.52), P=.68 — not significant
PFS: 7.0 vs 6.3 months, HR 1.02 (95% CI 0.73–1.42), P=.92 — not significant
Grade ≥3 fatigue: 8.5% (consolidation) vs 0% (observation)
PFS: 7.0 vs 6.3 months, HR 1.02 (95% CI 0.73–1.42), P=.92 — not significant
Grade ≥3 fatigue: 8.5% (consolidation) vs 0% (observation)
Adverse events
Main adverse events: Any grade toxicity significantly higher with pemetrexed consolidation. Grade ≥3 fatigue 8.5% vs 0%, grade ≥3 neutropenia 15.5% vs 0%. Hospitalization and treatment discontinuation rates higher in pemetrexed arm. No treatment-related deaths.
Conclusions
Pemetrexed consolidation after concurrent CRT provided no OS or PFS benefit over observation in stage III NSCLC, and caused significant excess toxicity. Consolidation cytotoxic chemotherapy after definitive CRT for stage III NSCLC is ineffective and should not be used.
Key Limitations
Key Limitations: Enrollment of only patients without progression after CRT introduces a favorable selection bias. The 4-cycle consolidation regimen was somewhat arbitrary — benefit at other durations is unknown. The pemetrexed dose (500 mg/m²) may not have been optimal for consolidation setting. This trial, combined with earlier docetaxel consolidation failures (Albain ASCO 2002), consistently demonstrates cytotoxic consolidation fails — but immunotherapy consolidation (PACIFIC) later succeeded, highlighting the importance of mechanism of action.
Clinical Context
HOG definitively ended the practice of consolidation cytotoxic chemotherapy after CRT for stage III NSCLC, following similar failures with docetaxel (Vokes ASCO 2002). The contrast with PACIFIC's success (durvalumab consolidation, HR 0.68 for OS) illustrates that consolidation strategy matters: cytotoxic agents fail while anti-PD-L1 immunotherapy transforms outcomes. Current standard: concurrent CRT (60 Gy + platinum-doublet) → durvalumab 12 months (PACIFIC regimen). No role for chemotherapy consolidation.
References
References: Hanna N et al, J Clin Oncol 2008 (HOG LUN 01-24)