Most patients with resectable NSCLC can benefit from preop chemo

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - Preoperative chemotherapy might help most patients with resectable non-small-cell lung cancer (NSCLC) survive longer, according to a new systematic review and meta-analysis.

Compared to surgery alone, surgery with neoadjuvant chemo significantly improved overall survival, time to distant recurrence, and recurrence-free survival in patients with resectable NSCLC, the authors reported online February 25 in The Lancet.

They saw an absolute survival increase of 5% at five years, from 40% to 45%.

"The results showed conclusively that preoperative chemotherapy is beneficial in these patients, representing a 13% reduction in the risk of death. This benefit was evident regardless of the patient's age, sex, performance status, histological type or clinical stage," said co-author Sarah Burdett, of the Medical Research Council Clinical Trials Unit of University College London, United Kingdom, in an email to Reuters Health.

"This is the first time the effect of preoperative chemotherapy against surgery alone for people with operable non-small cell lung cancer has been explored in an individual participant data systematic review and meta-analysis, the gold standard of systematic review," added Burdett.

Asked whether this should be the standard of care, she replied that "the benefit of preoperative chemotherapy is similar to that previously seen with postoperative chemotherapy, but further research is required regarding whether a combination of these treatments could have an even larger impact on survival."

The systematic review and meta-analysis included studies from early 1965 through May 2013 involving chemotherapy-naive NSCLC patients who were suitable for surgery and who had no previous malignancy.

All the analysis was by intention to treat, with no assessment of toxic effects.

Basing their meta-analysis on data from 2,385 patients in 15 randomized controlled trials, representing 92% of patients who were randomized from all known eligible trials, they found that preop chemo was a significant benefit to survival (hazard ratio 0.87, p=0.007), with no evidence of a difference between trials.

Patients appeared to benefit similarly regardless of age, sex, performance status, clinical stage or histology; and they survived similarly regardless of chemo regimen, scheduling, number of drugs, platinum agent used or whether they had postop radiotherapy.

Pre-op chemo significantly improved recurrence-free survival (HR 0.85, p=0.002) and time to distant recurrence (HR 0.69; p<0.0001), although most patients included were stage IB-IIIA.

Results for time to locoregional recurrence also favored the neoadjuvant chemo group, but not to a statistically significant extent (0.88; p=0.20).

Because most patients were in clinical stage IB, IIB and IIIA, the results were most reliable for these patients, Burdett said.

When the single estimated HR was combined with the overall result for the meta-analysis, the effect on survival remained the same (HR 0.87, p=0.006), based on 96% of patients.

The results so far seem to suggest similar effects with either preop or postop chemo, giving a choice of treatment options, the authors wrote, adding, "Clinicians might consider that preoperative chemotherapy is preferable for poorer prognosis patients with larger, more advanced stage tumours, less able to tolerate chemotherapy after surgery, or in regions where surgery waiting lists are longer."

"The potential benefit of preoperative chemotherapy would need to be balanced against possible toxic effects," they wrote. "However, although we were unable to assess toxic effects at the patient level in this study, trial reports for 13 of the included trials described mild or acceptable toxic effects and that chemotherapy was generally well tolerated."

In an editorial, Drs. Luis Paz-Ares and Jesus Corral of the Hospital Universitario Virgen del Rocio in Seville, Spain, wrote that the meta-analysis was well conducted, with scientifically sound and clinically relevant results.

"This analysis formally confirms that neoadjuvant chemotherapy improves overall survival to a similar extent as adjuvant treatment," they wrote.

"Nevertheless, despite the benefit shown, only one of 13 patients with early-stage lung cancer actually benefits from complementary chemotherapy, and at the expense of inducing relevant side-effects in all treated patients," they added.

"There is therefore an urgent need to develop predictive biomarkers to identify those patients who will profit from systemic treatment," they wrote.

SOURCE: http://bit.ly/1kS0B34

Lancet 2014.

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