“This prematurely closed phase III study indicates estimates of efficacy outcome in the range of those reported in other trials of preoperative treatment in the same setting of patients,” the authors comment.
They explain that their trial was terminated early because other randomized trials had documented positive results with adjuvant chemotherapy, and they felt it would be unethical to continue with a surgery-only arm.
Dr. Giorgio V. Scagliotti, with the University of Turin, Italy, and colleagues originally aimed to recruit 712 patients with stages IB-IIIA non-small-cell lung cancer (NSCLC) to compare outcomes with three preoperative cycles of gemcitabine plus cisplatin followed by radical resection versus surgery alone. At the point the study was closed, 129 patients had been assigned to chemotherapy plus surgery and 141 to surgery only.
Rates of progression-free survival at 3 years — the primary end point — were 52.9% for chemotherapy plus surgery and 47.9% with surgery alone, for a hazard ratio of 0.70 (p=0.003), the investigators report. Corresponding 3-year overall survival rates were 67.6% versus 59.8% (hazard ratio 0.63; p=0.02).
This advantage was seen almost entirely in patients with stage IIB/IIIA NSCLC, for whom the survival benefit at 3 years was 23.4%, the authors point out. Differences in those with stage IB/IIA disease were nonsignificant.
Serious adverse events related to chemotherapy or the procedure occurred in 12% of patients in the combination arm and 8% in the surgery-only arm, according to the report. The rate of grade 3 or 4 hematologic toxicity was 32% in the chemo group, 0% in the surgery alone group. Corresponding rates of grade 3 or 4 non-hematologic events were 16% and 11%.
“This randomized, controlled, multicenter phase III study showed that preoperative chemotherapy in early-stage NSCLC was feasible, tolerable, and active,” Dr. Scagliotti and colleagues conclude.
“Future developments in populations with these disease stages should focus on the utility of well-tolerated drugs and the collection of pharmacogenomic data to determine predictors for treatment outcome,” they add.
In an editorial, Dr. Gary M. Strauss with Tufts University School of Medicine in Boston, Massachusetts, discusses the results of this and other trials looking at adjuvant or induction chemotherapy in lung cancer patients undergoing surgery. “The evidence in support of surgical resection followed by adjuvant chemotherapy seems to be more convincing than for the use of induction chemotherapy in resectable NSCLC,” he suggests.
As for the current study, Dr. Strauss concludes, the findings “contribute only modestly to the question of how to optimally manage patients with resectable NSCLC.”
J Clin Oncol 2011;29.