According to results presented at a late-breaking session at the 40th annual meeting of the American Society of Clinical Oncology, the biologic agent Tarceva™ (erlotinib) improves survival as a single agent in patients with recurrent non-small cell lung cancer.

The epidermal growth factor receptor (EGFR) pathway is a complex biological pathway that is involved in the stimulation and growth of cells.  In many cancer cells, the EGFR is often over-expressed and/or has a mutation within the pathway. Researchers continue to evaluate the role and complexity of EGFR and cancer, as well as newer agents and combinations of agents that may target the EGFR pathway to control cancer growth.

Tarceva™ is an agent that targets the EGFR pathway and is in the last phases of clinical trials prior to FDA approval. Tarceva™ binds to the inner part of the EGFR, inhibiting stimulation of the pathway. Researchers speculate that Tarceva™ may play an important role in the treatment of some cancers, as two other EGFR inhibitors, Erbitux® and Iressa®, have recently been approved by the FDA for specific types of cancer. However, Tarceva™ is unique from other approved EGFR inhibitors in that it binds to the inside of the EGF receptor, instead of the outside portion like Erbitux® and Iressa®. Researchers are also evaluating Tarceva™ in combination with other agents that inhibit the EGFR through different mechanisms.

Researchers recently conducted a multi-institutional clinical trial evaluating Tarceva™ in the treatment of recurrent NSCLC. This trial included 731 patients that had received prior chemotherapy for NSCLC. Half of the patients had been treated with 2 or more prior chemotherapy regimens. Patients in this trial were treated with either Tarceva™ alone or placebo (inactive substitute) and were directly compared. The overall anti-cancer response rate was 9% for patients treated with Tarceva™, and the average duration of response was nearly 8 months.

Table 1 Tarceva™ versus placebo in recurrent NSCLC

Upon analysis of subgroups of patients and their respective outcomes to treatment, researchers noted that females, those with adenocarcinoma, and those who had never smoked had higher responses to Tarceva™. Patients who had never smoked also had a significantly improved survival while on Tarceva™ compared to those who smoked. Tarceva™ was very well tolerated, with rash and diarrhea being the most common side effects, the majority of which was mild to moderate in severity.

The researchers concluded that Tarceva™ as a single agent improves survival and is very well tolerated in patients with recurrent NSCLC. Several clinical trials are continuing to evaluate Tarceva™ in lung cancer, either in different stages of the disease or in combination with other agents. The researchers stated that future clinical trials evaluating Tarceva™ as therapy during a remission or early in the course of lung cancer are warranted.

Comments: This was one of the clinical trials that received publicity because the control group received only placebo rather than another chemotherapy drug.  The ethics of this approach are being debated among the oncology community with some very critical of the study design.  However, this study does show an effect for Tarceva™.  Whether or not the observed responses were better than would have been achieved by other salvage therapies is not known.

Reference: Shepherd F, Pereira J, Ciuleanu T, et al. A randomized placebo-controlled trial of erlotinib in patients with advanced non-small cell lung cancer (NSCLC) following failure of 1st or 2nd line chemotherapy. A National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trial. Proceedings from the 40th annual meeting of the American Society of Clinical Oncology, June 2004; Abstract #7022.