ASCO: No NSCLC Survival Benefit with Neoadjuvant Chemotherapy

CHICAGO, June 4 -- Neoadjuvant chemotherapy did not improve survival of patients with resectable non-small cell lung cancer (NSCLC) compared with surgery alone, researchers reported here.

The trial, which is the largest one of its kind to date, was powered to detect a 15% improvement in overall survival but the five-year survival was 44% in the chemotherapy plus surgery group versus 45% for surgery alone, said Marianne Nicolson, M.D., of the Aberdeen Royal Hospitals Trust in Aberdeen, Scotland, and colleagues.

Despite the lack of overall benefit, Dr. Nicolson said that neoadjuvant chemotherapy should still be considered for a select group of patients who could benefit from pre-surgical staging or patients in whom co-morbidities might delay adjuvant chemotherapy. The study was published simultaneously online in The Lancet.

The trial recruited 519 patients -- 61% stage 1, 31% stage II, and a little over 7% stage III at centers in Great Britain, the Netherlands, Germany, and Belgium. Patients were enrolled from July 1997 to July 2005; 258 were randomized to neoadjuvant chemotherapy and 261 to surgery alone.

Patients were assigned to one of six platinum-based regimens: Mitomycin (Mutamycin), vinblastine (Velban), and cisplatin (Platinol); mitomycin, ifostamide (Mitoxana), and cisplatin; cisplatin and vinorelbine (Navelbine); paclitaxel (Taxol) and carboplatin (Paraplatin); cisplatin and gemcitabine (Gemzar); or docetaxel (Taxotere) and carboplatin.

Surgery was recommended as soon as possible after randomization for those in the surgery-only group and four to six weeks after the last cycle of chemotherapy for patients in the chemotherapy arm.

Among the findings:

• 75% of patients randomized to neoadjuvant chemotherapy completed all three cycles.
• Partial or complete response was achieved in 49% of chemotherapy patients.
• About 20% of chemotherapy patients had evidence of downstaging.
• Only 2% of chemotherapy patients had progressive disease.
• Complete resection was achieved in 79% of the surgery patients and 81% of neoadjuvant chemotherapy patients.

"We can say that neoadjuvant chemotherapy had absolutely no effect on disease-free progression or overall survival," Dr. Nicolson said.

During the discussion Dr. Nicolson was asked about the high rate of brain metastases among the chemotherapy patients -- 21 patients versus 10 patients in the surgery arm.

She said that the investigators found that "surprising, but we don't really think that it is evidence of biologic effect. We cannot at this time fully explain it."

Roman Perez-Soler, M.D., chairman of oncology at Montefiore Medical Center and professor of medical oncology at Albert Einstein College of Medicine, said the findings "confirm what we have known: neoadjuvant chemotherapy does not add a survival benefit but is a good therapeutic option for patients based on lesion size and location."

Dr. Perez-Soler was not involved in the study.

In an accompanying comment in The Lancet, Frances Shepherd, M.D., and Penelope Bradbury, M.D., of University Health Network, Princess Margaret Hospital, and the University of Toronto in Canada, wrote that the study suggests that surgery should not be delayed by neoadjuvant chemotherapy.

"While a systematic review indicates a potential benefit from preoperative chemotherapy," they wrote, "the body of evidence to date favors postoperative chemotherapy."