Preoperative Chemotherapy Shows Promise in Early Lung Cancer

Giorgio V. Scagliotti, MD

Preoperative gemcitabine plus cisplatin followed by radical surgery is “feasible, tolerable, and active” in patients with early-stage non-small cell lung cancer (NSCLC), according to investigators.

Giorgio V. Scagliotti, MD, with the University of Turin, Italy, and colleagues randomized patients to three cycles of gemcitabine 1250 mg/m2 on days 1 and 8 every 3 weeks, plus cisplatin 75 mg/m2 on day 1 every 3 weeks followed by complete surgical resection or surgical resection alone.

The phase III study, known as Chemotherapy for Early Stages Trial (CHEST), recruited chemotherapy- and radiotherapy-naïve patients with stages IB, II, and T3N1 stage IIIA NSCLC. Individuals with N2 disease were excluded.

Despite improvements in treatment, lung cancer remains the leading cause of cancer deaths in most countries worldwide, Scagliotti and colleagues observed. Radical surgery is still the cornerstone of treatment for early NSCLC, but benefits only patients with localized disease without evidence of mediastinal lymph node involvement.

The authors said they were motivated to perform the CHEST study, in part, based on findings from a previous phase II European Organisation for Research and Treatment of Cancer (EORTC) study that had suggested that cisplatin/gemcitabine was a highly effective induction regimen for stage III NSCLC. The primary endpoint in their study was progression-free survival (PFS).

While the investigators had intended to enroll 712 patients, the study was prematurely terminated after 270 patients had been accrued. The decision to abort the study was made after three randomized, controlled trials on postoperative adjuvant therapy reported an improvement in overall survival (OS) for adjuvant chemotherapy in stages IB, II, and/or IIIA NSCLC, leading the CHEST investigators to conclude that it would be unethical to continue their study with a surgery-only treatment arm.

The CHEST study—with only 38% of the target sample size accrued—showed a chemotherapy response rate of 35.4%.

There was a highly significant benefit for induction chemotherapy with regard to PFS (hazard ratio [HR], 0.70; 95% CI, 0.50-0.97; P = .003). Overall survival was also superior in the chemotherapy arm (HR, 0.63; 95% CI, 0.4-0.92; P = .02).

The researchers also documented an absolute 3-year improvement in PFS of 5.1% in the chemotherapy- plus-surgery arm (52.9% vs 47.9%; adjusted HR for PFS, 0.70; P = .03) and 7.8% improvement in 3-year OS (67.6% vs 59.8%; adjusted HR for OS, 0.63; P = .02).

The benefit of preoperative chemotherapy was limited to the subgroup of patients with stages IIB or IIIA disease. In this subgroup, the 3-year PFS was roughly 19% better in the preoperative chemotherapy arm (55.4% vs 36.1%; P = .002). Differences in the IB/IIA group were nonsignificant, which the authors said was probably due to a lack of power.

The most common grade 3 or 4 chemotherapy-related adverse events were neutropenia and thrombocytopenia.

“Even with the limitation of early termination of enrollment, overall results suggested a positive effect of preoperative chemotherapy in early-stage NSCLC,” Scagliotti and colleagues wrote. In addition, the results were “in the range of” those reported in earlier trials of preoperative treatment in this setting.

Future research should focus on predictors of treatment outcome, the authors added.

Scagliotti GV, Pastorino U, Vansteenkiste JF, et al. Randomized phase III study of surgery alone or surgery plus preoperative cisplatin and gemcitabine in stages IB to IIIA non-small cell lung cancer [published online ahead of print November 28, 2011]. J Clin Oncol. 2012;30(2):172-178.