Concomitant CT/RT tops sequential for NSCLC patients

LOS ANGELES—Patients with locally advanced non-small-cell lung cancer and a good performance status have better overall survival and a lower risk of local-regional progression if they receive concomitant chemoradiation instead of sequential chemoradiation, according to a meta-analysis from the NSCLC Collaborative Group presented at this year's ASTRO meeting (abstract 9). The tradeoff was a higher risk of severe esophagitis.

"There is level I evidence of the survival benefit with the addition of either sequential or concomitant chemotherapy to radiotherapy vs radiotherapy alone among good performance status patients with stage III non-small-cell lung cancer," said presenting author Walter J. Curran, MD. "This meta-analysis seeks to compare the relative benefits of concomitant chemoradiation with sequential chemoradiation, based on those trials that have studied this question."

To be eligible for inclusion in the meta-analysis, trials had to be randomized, controlled trials comparing concomitant vs sequential chemoradiation among patients with unresected, locally advanced NSCLC who had not received previous treatment, said Dr. Curran, profesor of radiation oncologist at Jefferson Medical College, Thomas Jefferson University Hospital, Philadelphia.

In addition, accrual had to be completed before 2004. Individual patient data were used for the meta-analysis, and outcomes were determined according to intention to treat.

The investigators identified seven eligible trials, and individual patient data were available for six of them, for a total of 1,205 patients with a median follow-up of 5 years, Dr. Curran said.

Two trials used the same drugs and doses for concomitant and sequential chemotherapy. For sequential chemotherapy, all trials used at last cisplatin, induction chemotherapy was used in five trials, and consolidation in one.

For concomitant chemotherapy, cisplatin was used in five trials and carboplatin in one trial. One trial used consolidation chemotherapy after concomitant chemotherapy.

In terms of adverse events, patients receiving concomitant chemoradiation had a significantly higher incidence of grade 3 and 4 esophagitis than their counterparts receiving sequential chemoradiation (18% vs 4%; relative risk, 4.9), Dr. Curran reported.

"I think even more important was no difference in pulmonary toxicity of a grade 3 or 4 nature between the arms," Dr. Curran commented.

Overall survival, the primary endpoint of the meta-analysis, was significantly better with concomitant chemoradiation than with sequential chemoradiation (5-year rate, 15.1% vs 10.6%; HR 0.85).

Subgroup analyses did not reveal any significant differences in benefit by age, sex, performance status, histology, or stage, Dr. Curran said.

Progression-free survival, which Dr. Curran noted is "certainly an imperfect endpoint in this group of patients at best," was somewhat better with concomitant chemoradiation, compared with sequential chemoradiation, but not significantly so.

Local-regional progression-free survival, which he said was also a difficult endpoint to define in this population, was significantly better in the concomitant chemoradiation group (HR 0.77). Distant progression-free survival did not differ between groups.

The reference treatment

The findings, Dr. Curran concluded, suggest that relative to sequential chemoradiation, concomitant chemoradiation leads to better survival and less local-regional progression in the NSCLC population, at the expense of a higher rate of severe esophagitis.

"There is no clear evidence that the benefit or detriment of this treatment is identifiably different in any prespecified patient subgroup," he pointed out.

In this country, but perhaps less so around the globe, Dr. Curran said, "we would conclude that concomitant chemoradiation should be the reference treatment for patients with good performance status and locally advanced non-small-cell lung cancer."