Lung Cancer Study Could Change Standard of Care

Charlene Laino

June 03, 2003

June 3, 2003 (Chicago) -- In a finding that some oncologists say could change the standard of care for patients with resected non-small cell lung cancer (NSCLC), an international trial has shown for the first time that patients treated with cisplatin-based chemotherapy after surgery are significantly more likely to be alive five years later than those given surgery alone.

The 4.1% 5-year survival advantage conferred by adjuvant chemotherapy in NSCLS patients is slightly smaller than the 5% to 20% survival benefit, depending on the stage of disease, associated with giving chemotherapy after surgery to patients with breast and colon cancer.

Nevertheless, "the increase in survival is significant enough to recommend chemotherapy after surgery to appropriate lung cancer patients," said chief investigator Thierry le Chevalier, MD, from the Institut Gustave Roussy in Villejuif, France.

If adjuvant chemotherapy was given to all appropriate NSCLC candidates, 7,000 deaths worldwide could be prevented annually, Dr. Le Chevalier said here Monday at the 39th annual meeting of the American Society of Clinical Oncology.

About one third of patients with NSCLC are candidates for resection and adjuvant chemotherapy, according to Dr. Le Chevalier.

The rationale for the study, known as the International Adjuvant Lung Cancer Trial, was a 1995 meta-analysis on adjuvant chemotherapy in NSCLC that suggested a 5% improvement in survival at five years, he said.

From 1995 to 2000, 1,867 patients with stage I to III lung cancer in 33 countries were randomized to three or four cycles of cisplatin-based chemotherapy after complete resection of NSCLC, or surgery alone. Cisplatin was given in conjunction with etoposide in 56% of cases, vinorelbine in 27% of cases, vinblastine in 11% of patients, and vindesine in the remaining 6%.

About 80% of the patients, whose median age was 59 years, were men. Forty-seven percent had squamous cell carcinoma, 40% had adenocarcinoma, and the rest had other subtypes. Thirty-six percent of the patients had stage I disease, 25% had stage II, and 39% had stage III.

When the results were analyzed in September 2002, the median follow-up was 56 months, Dr. Le Chevalier said.

Median survival was 50.5 months for patients in the adjuvant chemotherapy group compared with 44.4 months for those in the surgery-alone group, the study showed. Median disease-free survival was 40.2 months and 30.5 months in the two groups, respectively.

At five years, 44.5% of those administered adjuvant chemotherapy were alive, 39.4% of whom had no progression of their disease, the researchers found. The five-year survival and disease-free survival rates were 40.4% and 34.3% in the surgery-only group, respectively.

This translates into a 4.1% absolute benefit in overall survival ( P < .03) and a 5.1% absolute benefit in disease-free survival ( P < .003) at five years, Dr. Le Chevalier said.

"If you look at the curve for survival or disease-free survival, there is a consistent benefit of administering chemotherapy over surgery alone," he added.

"We failed to identify any subgroup more likely to benefit," Dr. Le Chevalier said. There was no significant correlation between age, sex, performance status, type of surgery, stage or histology of disease, cisplatin dose, the combination of chemotherapy, or use of radiation therapy. Twenty-three percent of patients in the cisplatin arm had at least one grade IV toxicity, mainly neutropenia, and 0.8% died of treatment-related toxicity, he said.

Given these toxicities, "whether a 4% to 5% survival benefit is a risk worth taking is a big question," said Bruce Johnson, MD, director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute in Boston, Massachusetts, and moderator of a press conference at which the findings were discussed. "But [when] told that adjuvant chemotherapy will save 1 in 20 patients, most patients seem to want it.

"The information we now have suggests that we should offer adjuvant chemotherapy to patients, in a similar fashion that we offer adjuvant chemotherapy to patients with breast and colon cancer," Dr. Johnson said.

Clinical trials evaluating whether newer agents such as gemcitabine and taxanes may confer survival benefit with fewer toxicities are underway, the researchers noted.

ASCO 39th Annual Meeting: Abstract 6. Presented June 2, 2003.

Reviewed by Gary D. Vogin, MD