Adjuvant Chemotherapy Initiated 4 Months After NSCLC Resection Still Effective

Delayed adjuvant chemotherapy reduces mortality after complete non-small-cell lung cancer resection

medwireNews: Observational study findings indicate that patients derive benefit from adjuvant chemotherapy after complete resection of non-small-cell lung cancer (NSCLC) even when treatment is delayed for up to 4 months after surgery.

“Clinicians should still consider chemotherapy in appropriately selected patients that are healthy enough to tolerate it, up to 4 months after NSCLC resection”, say Daniel Boffa, from the Yale School of Medicine in New Haven, Connecticut, USA, and co-investigators.

COX analysis of data from a real-world population treated between 2004 and 2012 showed that the risk of mortality in patients with stage I–III disease was lowest when postoperative chemotherapy was initiated on day 50.

But beginning treatment on days 57–127 did not increase the risk of death compared with doing so on days 39–56, giving a nonsignificant hazard ratio (HR) of 1.037, the authors report in JAMA Oncology. Nor did initiation of chemotherapy before day 39 significantly alter mortality.

And propensity-matched pair analysis confirmed that receipt of adjuvant treatment significantly reduced the mortality risk compared with no postoperative chemotherapy regardless of whether treatment was begun on days 39–56 or 57–127, giving HRs of 0.672 and 0.664, respectively.

However, the researchers caution that “these findings should not be interpreted to mean that chemotherapy has an equivalent effect, irrespective of when it is given.”

“Although our study population was large and the post hoc analysis indicated appropriate statistical power, the chemotherapy effect is relatively small (5% difference in survival)”, they explain. “Therefore it is possible that a small but significant difference in survival exists based on when chemotherapy is given but is not able to be appreciated within this data set.”

The study included treatment-naïve patients entered into the National Cancer Database who began adjuvant multi-agent chemotherapy 18–127 days (median 48 days) after lobectomy or pneumonectomy for stage I (n=3073), II (n=5981) or III (n=3419) NSCLC.

In an accompanying editor’s note, Howard West, from the Swedish Cancer Institute in Seattle, Washington, USA, observes that clinical trial criteria often result in patients who are younger and have a better performance status than those typically seen in a clinic.

While acknowledging the drawbacks of observational studies, he emphasizes that “real-world data from large populations also provide a valuable corroboration of data obtained in randomized clinical trials of potentially nonrepresentative patients.”

“In the absence of prospective data for every patient, such retrospective data are valuable in offering the best evidence available for clinicians charged with the task of offering the best treatment recommendations for practical management of a broad population of patients that includes many who would not qualify for more restrictive clinical trials on which we rely to establish clinical standards.”

References

Salazar MC, Rosen JE, Wang Z, et al. Association of delayed adjuvant chemotherapy with survival after lung cancer surgery. JAMA Oncol; Advance online publication 5 January 2017. doi:10.1001/jamaoncol.2016.5829

West H(J). Bringing adjuvant chemotherapy for resected non-small-cell lung cancer into real-world practice – better late than never? JAMA Oncol; Advance online publication 5 January 2017. doi:10.1001/jamaoncol.2016.5798

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