Pre-op chemo vs. Post-op chemo!!!

[RandyW]

Preoperative Chemotherapy Improves 5-Year Disease-Free Survival Compared With Postoperative Treatment in NSCLC: Presented at ECCO-ESMO

By Chris Berrie

BERLIN -- September 24, 2009 -- Preoperative chemotherapy (preCT) shows beneficial trends for 5-year disease-free survival (DFS), compared with postoperative chemotherapy (postCT) in patients with clinical early stage non-small-cell lung cancer (NSCLC). In addition, preCT shows significantly better patient compliance over postCT.

The multicentre, randomised, prospective, open-label, phase 3 trial was presented here on September 22 at the joint 15th Congress of the European Cancer Organisation (ECCO) and 34th Congress of the European Society for Medical Oncology (ESMO).

Bartomeu Massuti, MD, Medical Oncology, Hospital General Universitari Alacant, Alicante, Spain, and colleagues assessed whether 3 cycles of postCT or preCT improved 5-year DFS, each compared with surgery alone. Secondary endpoints included toxicities, overall survival (OS), and prognostic and predictive values of molecular markers.

Patients with NSCLC (n = 624) aged 18 years and older were stratified by tumour size (<3>5 cm) and age (<60>=60 years), and randomised to surgery alone (n = 212), postCT (n = 211) or preCT (n = 201). Of the patients, 200, 201, and 181 underwent surgery, respectively.

Chemotherapy consisted of paclitaxel 200 mg/m2/3 hours, plus carboplatin area under the curve (AUC) 6 every 3 weeks, for 3 cycles. Postoperative thoracic radiotherapy was allowed for patients with N2 disease.

Surgery across treatment groups was mainly lobectomy/bilobectomy (~70%) or pneumonectomy (~25%), with no difference in surgery-related deaths (6%, 7%, 5%, respectively).

In the intention-to-treat patient population, preCT provided a radiological response of 53% (complete, 9%; partial, 44%; stable, 32%; progressive, 5%), with 9.5% pathological complete response.

Treatment compliance was significantly greater for preCT than postCT (97% vs 66%; P < .0001). "The reasons for the patients who did not receive postoperative chemotherapy were mainly surgery related [54%]," added Dr. Massuti.

A 5-year DFS of 38.3% was seen for preCT versus 34.1% for surgery alone (P = .176). This was not seen for postCT (36.6%; P = .73). No differences in 5-year OS were seen across treatments (surgery alone, 44.0%; postCT, 45.5%; and preCT, 46.6%).

For stage T3N1M0 patient subgroup, this trend almost reached significance over surgery alone for preCT (P = .07), but not for postCT (P = .54).

Chemotherapy toxicity was mild in both arms, with similar levels of grade 3/4 toxicity across preCT and postCT, and with postoperative mortality similar across treatment arms.

Dr. Massuti noted the need for addressing chemotherapy benefit according to disease stage. Indeed, as he said, "New staging procedures and molecular markers could refine the design of new trials dealing with preoperative chemotherapy in early stage NSCLC."

Funding for this study was provided by Bristol Myers Squibb, Spain.

[Presentation title: Assessing the Value of Pre-Operative Chemotherapy in Early Stage Non-Small-Cell Lung Cancer: Mature Data and Prognostic Factors Analysis of a Phase III Randomised Trial of Surgery Alone vs Pre-Operative Paclitaxel/Carboplatin (PC) vs Postoperative PC. Final NATCH Data. A Spanish Lung Cancer Group (SLCG) Trial. Abstract 21LBA]