More Support for Adjuvant Chemo in Resected NSCLC

Zosia Chustecka

September 18, 2010

March 23, 2010 — A new meta-analysis adds support for the use of adjuvant chemotherapy in patients with resected nonsmall-cell lung cancer (NSCLC).

"Although the survival benefit seems small, worldwide adoption of adjuvant chemotherapy could save up to 10,000 lives every year," said Gregory Kalemkerian, MD, from the Department of Internal Medicine at the University of Michigan in Ann Arbor. He was writing in an editorial that accompanies the results, both of which were published online March 24 in The Lancet.

But adjuvant chemotherapy is already used in this patient population. Hence, the new results, which build on 2 previous meta-analyses from the same group, "add little to clinical practice," the Dr. Kalemkerian writes.

Medscape Oncology blogger H. Jack West, MD, medical director of thoracic oncology at the Swedish Cancer Institute in Seattle, Washington, agrees: "What has the meta-analysis told us, beyond confirming what was already established by nearly every thoracic oncologist?"

"The benefit of adjuvant chemotherapy in appropriate patients with sufficiently high-risk disease who are fit enough to consider postoperative chemotherapy has already been well established by several well conducted prospective randomized phase 3 trials, some using relatively current chemotherapy regimens," Dr. West said. "It is unclear to me what value there is in adding a wide range of very old and less well conducted studies that use varied staging and questionable treatment regimens to address the issue."

We should not confuse 'more data' with 'better data.'

"This question had already been answered before this meta-analysis, and to me the only issue that this clarifies is that the benefit is still present, despite diluting the results of high-quality studies with multiple inferior ones," Dr. West said. "I would be very surprised if someone who previously doubted the utility of adjuvant chemotherapy became convinced on the basis of this meta-analysis."

"We should not confuse 'more data' with 'better data'," Dr. West told Medscape Oncology.

New Paper Comprises 2 Meta-Analyses

The new paper actually comprises 2 meta-analyses, and both reach the same conclusion — that the addition of adjuvant chemotherapy after surgery for patients with operable NSCLC improves survival, irrespective of whether radiotherapy was included.

The first of these new meta-analyses looked at adding chemotherapy alone after surgery in 8447 patients (3323 deaths) from 34 clinical trials. It found an absolute increase in survival of 4% at 5 years, from 60% to 64% (hazard ratio [HR], 0.86; P < .0001). The second meta-analysis looked at chemotherapy plus radiotherapy after surgery in 2660 patients (1909 deaths) from 13 trials. It also found an absolute increase in survival of 4% at 5 years, from 29% to 33% (HR, 0.88; P =.009).

These results are reported by Sarah Burdett, MSc, from the Medical Research Council Clinical Trials Unit in London, United Kingdom, and Jean-Pierre Pignon, MD, from the Institut Gustave Roussy in Villejuif, France, on behalf of the NSCLC Meta-Analyses Collaborative Group.

This group has reported 2 previous meta-analyses, Dr. Kalemkerian points out.

In 1995, they reported a 5% improvement in 5-year survival, which was not statistically significant (HR, 0.87; P = .08) with cisplatin-based chemotherapy (BMJ. 1995;311:899-909).

More recently, the same group reported the LACE meta-analysis (J Clin Oncol. 2008;26:5043-5051), which included only trials that used modern cisplatin-based regimens, and found a significant 5-year survival benefit of 5.4% (HR, 0.89; P = .005).

The latest results "add further support to the use of adjuvant chemotherapy in patients with resected NSCLC," the editorialist concludes.

Chemotherapy Recommended

In his editorial, Dr. Kalemkerian also summarizes the current clinical practice.

"Adjuvant platinum-based chemotherapy can be recommended for patients who have complete resection of stage 2 to 3 NSCLC and have uncomplicated recovery with good performance status within 3 months of surgery," he writes.

"Treatment can be considered for patients with larger tumors (T2b, T3) without lymph node involvement," he adds.

However, the scarcity of data means that adjuvant treatment cannot be recommended for patients with stage 1a disease, Dr. Kalemkerian warns. "Similarly, data for patients older than 70 years are sparse, and adjuvant chemotherapy should be approached with caution in the population."

Future studies should focus on the role of adjuvant therapy in these subgroups, and on the use of biomarkers to select patients who will benefit from specific treatments, he suggests.

The researchers have disclosed no relevant financial relationships.

Lancet. Published online March 24, 2010.

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