Sequential vs. Concurrent Therapy for Non–Small-Cell Lung Cancer

Since the mid-1990s, patients with locally advanced nonmetastatic non–small-cell lung cancer (NSCLC) have typically been treated with thoracic radiation therapy and then concurrent or sequential chemotherapy and radiation. Prior meta-analyses have shown that adding chemotherapy to radiation therapy, either sequentially or concurrently, improved survival for these patients (Ann Oncol 2006; 17:473 and BMJ 1995; 311:899).

Now, the NSCLC Collaborative Group has performed a meta-analysis of six randomized trials (involving 1205 patients) that compared outcomes associated with sequential versus concurrent chemoradiation. The chemotherapy regimens varied among the trials, but all regimens incorporated a platinum agent.

At median follow-up of 6 years, the results were as follows:

• Concurrent therapy conferred a significant survival benefit compared with sequential therapy (hazard ratio, 0.84; 95% confidence interval, 0.74–0.95; P=0.004).

• The survival benefit corresponded to a 5.7% improvement at 3 years (23.8% with concurrent therapy vs. 18.1% with sequential therapy) and a 4.5% improvement at 5 years (15.1% with concurrent therapy vs. 10.6% with sequential therapy).

• Progression-free survival was only numerically better with concurrent therapy (HR, 0.90; 95% CI, 0.79–1.01; P=0.07).

• Local control was better with concurrent therapy (HR, 0.77; 95% CI, 0.62–0.95; P=0.01), but distant progression was the same with both treatments.

• Grade 3–4 esophageal toxicity was more common with concurrent therapy (relative risk, 4.9; 95% CI, 3.1–7.8; P<0.001).