Patients with non–small-cell lung cancer (NSCLC) for whom adjuvant chemotherapy must be delayed for as long as 18 weeks have mortality outcomes that are no worse than those of patients who start chemotherapy soon after surgery, and those who undergo delayed chemotherapy have a significantly lower risk for death than patients who have no chemotherapy at all, investigators report.

A retrospective review of data on 12,473 patients with previously untreated NSCLC showed that there were no significant differences in 5-year overall survival (OS) estimates among patients who started multi-agent chemotherapy at 18-38 days postoperatively, from 39 to 56 days after surgery (the reference interval), or from 57 to 127 days after surgery, reported Daniel J. Boffa, MD, of Yale University, New Haven, Conn., and his colleagues.

In addition, when they used propensity score matching to pair patients who received chemotherapy with patients who did not undergo chemotherapy, they found that even late chemotherapy was associated with a significantly lower risk for death.

“Clinicians should still consider chemotherapy in appropriately selected patients that are healthy enough to tolerate it, up to 4 months after NSCLC resection. Further study is warranted to confirm these findings,” the investigators concluded (JAMA Oncol. 2017 Jan. 5 doi: 10.1001/jamaoncol.2016.5829 ).

In the retrospective review of records from the National Cancer Database, the investigators limited the study to patients for whom chemotherapy is typically prescribed: those with lymph node metastases, tumors 4 cm or larger, and/or local extension of disease. They looked at the association between the time to initiation of adjuvant chemotherapy and survival using Cox modeling with restricted cubic splines, a validated statistical method for evaluating links between survival and independent variables.

Dr. Boffa and his associates found that the unadjusted Kaplan-Meier 5-year OS estimates did not differ between the groups, at 53% for the early chemotherapy group (hazard ratio [HR] vs. the reference group, 1.009, P = .79), 55% for the reference group, and 53% for the later chemotherapy group (HR 1.037, P = .27).

Comparing adjuvant chemotherapy timing on the efficacy of surgery alone in patients matched by tumor stage and other features, the researchers found that chemotherapy started during any of the three intervals was associated with an approximately 34% reduction in risk of death compared with no chemotherapy (HR for the respective time intervals 0.672, 0.645, and 0.664; P less than .001 for each comparison).

The study helps to clarify for clinicians the benefits of adjuvant chemotherapy in select patients with NSCLC in a real-world setting, Howard (Jack) West, MD, of the Swedish Cancer Institute, Seattle, said in an accompanying editorial (JAMA Oncol. 2017 Jan. 5 doi: 10.1001/jamaoncol.2016.5798 ).

“While retrospective data cannot define the benefit of delayed adjuvant chemotherapy with the clarity of a prospective randomized trial, we must remember that in the land of the blind, the one-eyed man is king; these limited data inject an evidence-based answer for a very common clinical question for which we have been forced by necessity to rely only on our best judgments,” he wrote.

The study was internally supported. The authors and Dr. West reported no conflict of interest disclosures.