IASLC: Myths Abound in NSCLC Treatment with Erlotinib

SEOUL, South Korea, Sept. 6 -- Erlotinib (Tarceva) is a viable candidate across the board for second-line treatment of non-small-cell lung cancer (NSCLC), oncologists said here.

The National Cancer Institute of Canada-Clinical Trials Group (NCIC-CTG) study that led to approval of erlotinib for second-line treatment showed some groups benefited more than others, which led some to use these features for patient selection, said Keunchil Park, M.D., of Samsung Medical Center in Seoul.

But, he and other oncologists at an industry-sponsored satellite symposium held in conjunction with the International Association for the Study of Lung Cancer meeting here suggested such patient exclusion is based on myth rather than robust clinical evidence.

Erlotinib is indicated by the FDA as monotherapy for the treatment of patients with locally advanced or metastatic NSCLC after failure of both platinum-based and docetaxel chemotherapies.

One "myth" is that erlotinib is only effective in women with adenocarcinoma, said Romn Prez-Soler, M.D., of the Albert Einstein College of Medicine in New York.

The NCIC-CTG study showed that women had more than twice as high a response rate as men although adenocarcinomas were more than three times as likely to respond as other histological types of NSCLC.

But the response rate was not a good indicator of benefit by itself with erlotinib, Dr. Prez-Soler said.

For overall survival, men and women had an identical 20% reduction in risk (P=0.01 and P=0.03, respectively), and both adenocarcinomas and squamous-cell carcinoma showed a significant benefit for erlotinib (P=0.008 and P=0.0007).

The same was true for the greater erlotinib response rate seen among Asian than non-Asian patients (18.9% versus 7.5%) that still yielded significant overall survival benefit for non-Asians (hazard ratio 0.8).

Although current and ex-smokers in the NCIC-CTG trial did not have a significant overall survival advantage with erlotinib (HR 0.9, P=0.14), Dr. Prez-Soler said, "benefit cannot be ruled out."

Rather, he suggested that this group might need higher erlotinib dosing than nonsmokers. Pharmacokinetic studies in healthy volunteers in a separate study showed that smokers got at most 65.2% of the drug exposure as did nonsmokers from the same dose.

"The most likely explanation is that cigarette smoke induces liver enzymes that are responsible for metabolism of Tarceva," Dr. Prez-Soler said. "Dose escalation may be required in current smokers, and trials are ongoing to investigate this possibility."

Another myth is that erlotinib is effective only in tumors positive for epidermal growth factor receptor (EGFR) expression measured by immunohistochemistry or fluorescence in situ hybridization (FISH), said Denis Soulires, of the Centre Hospitalier de l'Universit de Montreal.

But, in the same NCIC-CTG study, tumors with high expression of EGFR did not survive significantly longer than those with low expression (P=0.12), he said.

Erlotinib was not significantly more effective than placebo in tumors without EGFR tyrosine kinase mutations (HR for survival 0.74, P=0.924), but there was not a significant interaction between mutation presence or absence and survival (P=0.47).

Furthermore, another trial suggested that tyrosine kinase mutations might be prognostic rather than predictive of response, Dr. Soulires said.

"None of the suggested biomarkers or patient characteristic can be reliably used to predict clinical benefit," he said. "Selection of patients on the basis of the current data cannot yet be justified in clinical practice."