Stage IIIB NSCLC treatment is definitive chemo-radiotherapy (CRT). In our SAKK 16/01 trial, neoadjuvant chemotherapy (CT) followed by neoadjuvant accelerated radiotherapy (RT) and surgery showed a median survival of 28.7 months (mos) in selected stage IIIB patients (pts). These promising results are the rationale for the current trimodality concept, introducing concomitant cetuximab (CET) to neoadjuvant CRT.
Pts with pathologically proven resectable stage IIIB (T4N0-3M0 or T1-4N3M0, 6th TNM) NSCLC, PS 0-1, and adequate organ function were treated with 3 cycles of neoadjuvant CT (cisplatin 100 mg/m2 and docetaxel 85 mg/m2 d1, q3w) followed by accelerated concomitant boost RT (44 Gy in 22 fractions in 3 weeks), both with concomitant weekly CET (250mg/m2) and subsequent surgery. The primary endpoint was progression-free survival (PFS) at 1 year (yr).
69 pts were treated in 11 Swiss centers. 2/3 were men, median age was 60 yrs. Histology was squamous in 41% and adenocarcinoma in 49%, with T4 disease in 61%, N3 in 46% and both in 7%. A median relative total dose intensity of 99% of CT and 91% of CET was delivered. Per protocol RT was delivered to 95% of pts. 57 (83%) pts underwent surgery, with complete resection (R0) in 74% and a postoperative 30d mortality of 4%. Response rate after CT-immunotherapy was 57% and 64% after CRT-immunotherapy (CRT-I). Major pathologic response was found in 36% of the resected pts. 1-yr PFS based on Kaplan-Meier estimation was 50% (95% CI: 37%-62%). Median PFS was 12 mos (95% CI: 9-16), median OS was 21 mos (95% CI: 14-25), with a 2 and 3-yr survival of 41% and 30%, respectively.
This is one of the largest prospective phase II trials to evaluate the role of induction CRT-I and surgery in resectable stage IIIB disease, and the first to associate concurrent CET to the neoadjuvant strategy. Trial treatment is feasible with excellent adherence to the protocol and promising clinical and pathological response rates, PFS and OS, supporting an aggressive approach including surgery in selected IIIB pts. As compared to our previous SAKK 16/01 experience, the addition of CET does not improve the outcome of this group of locally advanced NSCLC pts.
Clinical trial identification
SAKK 16/08, NCT01059188, original version dated: 24.08.2009, including amendments: 04.07.2013.
Legal entity responsible for the study
Swiss Group for Clinical Cancer Research (SAKK)
All authors have declared no conflicts of interest.