Chemotherapy Questions Linger in Early NSCLC

Publication
Article
Oncology Live®September 2013
Volume 14
Issue 9

The optimal use of adjuvant chemotherapy for patients with early-stage non-small cell lung cancer remains unresolved, with several clinical trials under way in Europe aimed at identifying ways to better select patients for treatment

Silvia Novello, MD, PhD

The optimal use of adjuvant chemotherapy for patients with early-stage non-small cell lung cancer (NSCLC) remains unresolved, with several clinical trials under way in Europe aimed at identifying ways to better select patients for treatment, according to Silvia Novello, MD, PhD.

Novello, an assistant professor in the Thoracic Oncology Unit at San Luigi Hospital at the University of Turin in Italy, discussed the landscape in adjuvant treatment for patients with stages I-III disease in a presentation and subsequent interview at the 14th International Lung Cancer Congress, held July 25-27 in Huntington Beach, California.

As it stands now, chemotherapy is indicated after surgical intervention for patients with nonmetastatic stage II or III disease, and the most effective duration of therapy is three to four cycles, said Novello. Adjuvant platinum-based chemotherapy improves survival in completely resected stage II and III NSCLC, although the impact “is not impressive,” said Novello, citing the findings of two meta-analyses that demonstrated a 4% increase in the five-year survival (Lancet. 2010;375[9722]:1267-1277).

However, the evidence does not support adjuvant chemotherapy in stage IA, and stage IB is a “gray zone,” Novello indicated. In fact, she cited a study showing that adjuvant chemotherapy may be detrimental for stage IA patients, although she said only 13% of participants in that cohort received the best potential regimen of cisplatin and vinorelbine (J Clin Oncol. 2008;26[21]:3552-3559).

Thus far, the search for predictive biomarkers has not generated a definitive marker, but efforts to do so are continuing, Novello said. She is among the key investigators in the ITACA trial in which researchers in Germany and Italy are randomizing up to 700 patients with completely resected stage II-IIIA NSCLC to standard chemotherapy versus a regimen guided by pharmacogenomics analyses (J Clin Oncol. 2012:30[suppl; abstr TPS7109]).

Patients are stratified first by excision-repair cross-complementing-1 (ERCC1) gene expression and then by thymidilate synthase (TS) levels into four treatment groups: (1) high ERCC1/high TS, taxanes versus the control regimen of a cisplatin- based doublet; high ERCC1/low TS, pemetrexed versus control; low ERCC1/high TS, cisplatin/ gemcitabine versus control; and low ERCC1/ low TS, cisplatin/pemetrexed versus control.

In the phase III SCAT trial, researchers in Spain are seeking to customize chemotherapy for an estimated 432 patients with resected tumors with lymph node involvement of N1-N2 (stages IIA-IIIA) based on BRCA1 mRNA expression levels (NCT00478699).

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