phase iii study of concurrent chemotherapy and radiotherapy (ct/rt) versus ct/rt followed by...
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Phase III Study of Concurrent Chemotherapy and Radiotherapy (CT/RT) versus CT/RT followed by Surgical Resection for Stage IIIA(pN2) NSCLC Outcomes Update of North American Intergroup Trial 0139 (R9309) Conducted by: RTOG (chair), SWOG, NCIC CTG, ECOG, CALGB and NCCTG Radiation Therapy Oncology Group Slide 2 Lung Intergroup Trial 0139 Rationale Patients with stage III NSCLC and clinically- evident N2 disease have poor outcomes with surgery or radiotherapy (RT) alone Chemotherapy (CT) plus RT is standard for pathologically-confirmed N2 nodes (pN2) Surgical resection after CT/RT, although promising in phase II trials, is controversial due to increased morbidity and mortality Slide 3 Lung Intergroup Trial 0139 Objectives 1.Determine if resection after CT/RT results in improved outcome compared to CT plus full-course RT (arms based on SWOG 8805 and SWOG 9019) 2.Analyze progression-free, overall, and long-term survival; toxicity; and patterns of failure Slide 4 Lung Intergroup Trial 0139 Eligibility Criteria T1-3, pN2, M0 non-small cell lung cancer Resection technically feasible FEV1 >2.0 liters, or, predicted post-resection FEV1 800 cc Medically fit Slide 5 Lung Intergroup Trial 0139 Study Design STRATIFY KPS 70-80 vs 90-100 T1 vs T2 vs T3 RANDOMIZE RE-EVALUATE RE-EVALUATE 2-4 weeks after 7 days before completion of RT completion of RT Induction CT/RT Cisplatin, 50 mg/m 2 IV d1, 8, 29, 36 Etoposide, 50 mg/m 2 IV d1-5, 29-33 Thoracic RT, 45 Gy (1.8 Gy/d), begin d1 Slide 6 Lung Intergroup Trial 0139 Study Design No progression at re-evaluation Surgical Resection Continue RT to 61 Gy without interruption CONSOLIDATION cisplatin plus etoposide X 2 cycles Slide 7 Lung Intergroup Trial 0139 Statistical Considerations Sample size assumed 25% 2-year survival for CT/RT and 10% absolute improvement by the addition of surgery 80% statistical power and 0.05 significance level Final accrual 484 eligible patients Slide 8 Lung Intergroup Trial 0139 Results Opened 3/94 and closed 11/01 Accrual longer than planned with more events, thus closure allowed at n = 429 First analysis in 2003 reported better PFS, but not OS, for surgical arm Second planned analysis this report: Median follow-up: 81 months All patients followed >2.5 years Slide 9 Lung Intergroup Trial 0139 Patient and Tumor Characteristics* Randomized/Eligible CT/RT/S CT/RT Female Age median yrs/ 70 KPS 70-80 Weight loss 5 kg T3 tumors Squamous histology LDH abnormal 429/396 (93%) 202 194 144 (36%) 60/63 (16%) 48 (12%) 84 (21%) 48 (12%) 129 (33%) 72 (18%) *balanced in both arms Slide 10 Lung Intergroup Trial 0139 Eligible for thoracotomy177 (88%) Thoracotomy performed164 (81%) Complete resection144 (71%) Incomplete resection 11 (5.5%) No resection 9 (4.5%) Eligible for consolidation CT/RT 179 (92%) Commenced consolidation155 (80%) Treatment Delivered ARM 1 (n=202) ARM 2 (n=194) Slide 11 Lung Intergroup Trial 0139 Treatment CT/RT/S CT/RT p-value (n=202) (n=194) Induction 191 (95%) 177 (92%) NS chemotherapy Consolidation 112 (56%) 144 (75%) p