Randomized phase II trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed (CPx) versus cisplatin and vinorelbine (CVb): TREAT.

7002 Background: Adjuvant chemotherapy is beneficial in early stage NSCLC, but toxicity and dose delivery are an issue in many patients. Therapy with CPx showed clear activity and good tolerability in advanced NSCLC (Scagliotti, JCO 26:3543,2008). Aim of this phase II trial was to compare dose delivery and clinical feasibility of CPx and CVb in the adjuvant setting. Methods: R0 resected NSCLC patients, stage pIB-T3N1, were randomized to 4 cycles of C(50 mg/m2 d1+8)/Vb(25 mg/m2 d1,8,15,22) q4 weeks (Winton, NEJM 352:2589,2005) or to 4 cycles of C(75 mg/m2)/Px(500 mg/m2)d1 q3 weeks. Primary objective was clinical feasibility (no grade (G) 4 neutro-/thrombocytopenia >7 days or bleeding, no G3/4 febrile neutropenia, no G3/4 non-hematological toxicity; no premature withdrawal; no death). Secondary objectives were drug delivery and efficacy. Results: 132 pts (74% male, mean age 59 years) were randomized (10/06-12/09, 16 sites, majority before Px-label change to non-squamous). Surgery: lobectomy 83%, pneumonectomy 14%, complex resections 3%. Tumor stages: 38% IB, 10% IIA, 47% IIB, 5% pT3pN1; histology: 43% squamous, 57% non-squamous. Feasibility rate was 95.5% (95%CI 87.5-99.1) for CPx compared to 75.4% (63.1-85.2) for CVb (p=0.001). Prevalence of G3/4 toxicities for CPx vs. CVb were: hematological 10% vs. 74% (p<0.001); non-hematological 33% vs. 31% (p=0.798). Delivery of absolute intended dose was higher for CPx (74.6%, 95%CI 62.5-84.5) than for CVb (20.0%, 11.1-31.8) (p<.0001). Mean doses (mg) for CPx were C: 272 (90% of planned, dose density 23 mg/m2/wk) and Px: 1810 (90%, 150 mg/m2/wk); for CVb were C: 263 (66% of planned dose, 16 mg/m2/wk) and V: 256 (64%, 16 mg/m2/wk). Median number of cycles was 4 for CPx (11.2 wks) and 3 for CVb (9.9 wks). Time to withdrawal from therapy differed significantly between arms favoring CPx (p<0.001). During early follow-up (4 months), relapses and deaths occurred in 1 and 1 patient for CPx and in 3 and 2 for CVb. Conclusions: Adjuvant chemotherapy with CPx is safe and feasible with less toxicity and superior dose delivery compared to CVb, mostly due to Vb delivery failure (d 15, 22). For efficacy, longer follow-up data have to be awaited.