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Delayed adjuvant chemotherapy does not increase NSCLC mortality
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Adjuvant chemotherapy initiated 7 to 18 weeks after resection of non–small cell lung cancer still benefited patients who recovered slowly from surgery and did not increase risk for mortality, according to results of a retrospective observational study.
“Patients with lung cancer in particular may be slow to regain their preoperative performance status after surgery, secondary to advanced age, prevalence of smoking-related lung disease and higher risk for postoperative complications,” Daniel J. Boffa, MD, associate professor of thoracic surgery in the department of surgery of Yale School of Medicine, and colleagues wrote. “Therefore, the relationship between the time to initiate adjuvant chemotherapy and its effectiveness is highly relevant to clinical practice.”
Boffa and colleagues used the National Cancer Data Base to evaluate data from 12,473 treatment-naive patients (median age, 64 years; interquartile range [IQR], 57-70) with stage 1 (n = 3,073), stage 2 (n = 5,981) or stage 3 disease (n = 3,419) to measure the relationship between the timing of postoperative chemotherapy and 5-year mortality. Each patient received multiagent chemotherapy 18 to 127 days after NSCLC resection.
The median time to chemotherapy postsurgery was 48 days (IQR, 37-62; range, 18-127). Median follow-up for surviving patients from day of surgery was 46 months (IQR, 28-73).
Researchers first used an adjusted adjuvant Cox model with adjuvant chemotherapy timing, separated into 7-day intervals, where patients in the 49-days interval were used as the reference group because they represented the cohort median. Results of this analysis showed no correlation between mortality and chemotherapy timing.
Researchers then used a Cox model with restricted cubic splines in which patients were categorized into three groups based on initiation of therapy: reference (39 to 56 days), earlier (18-38 days) or later (57-127 days).
This analysis showed lowest risk for mortality when therapy started 50 days postsurgery (95% CI, 39-56). However, patients who began chemotherapy after this interval in the later group did not have increased risk for mortality (HR = 1.03; 95% CI, 0.97-1.1).
To validate adjuvant chemotherapy efficacy, researchers compared patients with a separate cohort of 19,001 patients with NSCLC treated with surgery alone.
Analysis of 3,976 propensity-matched pairs showed patients who received chemotherapy during the later interval had a lower risk for mortality compared with patients treated with surgery only (HR = 0.66; 95% CI, 0.62-0.7). Further analysis showed patients who received adjuvant chemotherapy, regardless of timing, had decreased mortality risk compared with patients who received surgery only (early group, HR = 0.67; 95% CI, 0.62-0.72; reference group, HR = 0.64; 95% CI, 0.6-0.68).
Unadjusted Kaplan-Meier 5-year OS estimates did not show significant differences between patients who received earlier therapy (53%) compared with the reference group (55%) or later group (53%).
“Clinicians should still consider chemotherapy in appropriately selected patients who are healthy enough to tolerate it, up to 4 months after NSCLC resection,” Boffa and colleagues wrote.
However, retrospective data cannot fully define the benefit of delayed treatment compared with a prospective randomized trial, forcing clinicians to use their best judgment in these cases, Howard West, MD, medical director of the thoracic oncology program at Seattle Cancer Institute, wrote in a corresponding editor’s note.
“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,” West wrote. “But real-world data from large populations also provide a valuable corroboration of data obtained in randomized clinical trials of potentially nonrepresentative patients.”
He added that without prospective data for every patient, retrospective data are valuable in that they offer “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.”– by Melinda Stevens
Disclosure: The researchers and West report no relevant financial disclosures.
Photo by Yale School of Medicine.
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