This article is more than 5 years old. Information may no longer be current.
FDA approves Tarceva for first-line treatment in patients with NSCLC
Click Here to Manage Email Alerts
The FDA recently approved erlotinib as a first-line treatment for patients with metastatic non–small cell lung cancer whose tumors exhibit epidermal growth factor receptor exon 19 deletions or exon 21 substitution mutations.
This indication for erlotinib (Tarceva; Genentech, Astellas Pharma) is being approved in tandem with the cobas EGFR Mutation Test, a companion diagnostic test for patient selection.
Alberto Gutierrez
“The approval of the cobas EGFR Mutation Test will allow physicians to identify non–small cell lung cancer patients who are candidates for receiving Tarceva as first-line therapy,” Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, said in a press release. “Companion diagnostics play an important role in determining which therapies are the safest and most effective for a particular patient.”
Approval for erlotinib was based on the results of a randomized, multicenter, open-label trial evaluating erlotinib (n=86) against platinum-based doublet chemotherapy (n=88) in patients with metastatic NSCLC whose tumors had EGFR exon 19 deletions or exon 21 (L858R) substitution mutations determined by a clinical trial assay.
Patients were randomly assigned to erlotinib 150 mg/day orally or platinum-based doublet chemotherapy. Tumor samples from 134 patients were tested retrospectively by the cobas EGFR Mutation Test. The trial’s primary endpoint was investigator-assessed PFS, whereas secondary endpoints included OS and objective response rate (ORR).
According to study results, the median PFS was 10.4 months in the erlotinib group and 5.2 months in the platinum-based chemotherapy group (HR=0.34; 95% CI, 0.23-0.49). The median OS was 22.9 months in the erlotinib group and 19.5 months in the platinum-based chemotherapy arm (HR=0.93; 95% CI, 0.64, 1.35). The ORR was 65% in the erlotinib group and 16% in the platinum-based chemotherapy group.
Most patients in the platinum-based chemotherapy group (82%) received an EGFR tyrosine kinase inhibitor after investigator-determined disease progression. Analysis of PFS in patients who tested positive in the cobas EGFR Mutation Test was consistent with the primary analysis.
The most common adverse effects observed in patients who received erlotinib included rash, diarrhea, asthenia, cough, dyspnea and decreased appetite.
Perspective
Back to Top
Heather Wakelee, MD
This FDA approval is a great thing for patients and those of us treating them. It represents what we have already been doing in practice for a couple of years.
In the past, if I wrote a prescription for erlotinib (Tarceva; Genentech, Astellas Pharma) for a patient with a known EGFR-activating mutation as first-line therapy, normally it would get covered by insurance, but there was always a question of whether it would be covered. This approval takes away that question and allows us to do what we know is the right clinical practice for those patients.
Multiple clinical trials have proven the principle that, for patients with a known EGFR mutation, a first-line EGFR tyrosine kinase inhibitor is going to get a higher response rate and PFS than chemotherapy. This approval gives us the opportunity to do that on-label.
A big problem we have in treating these patients is the fact resistance develops, usually in less than a year. With this approval, we can do more testing of drugs that can potentially be combined with erlotinib to delay that resistance.
In the past, we had been hampered in those studies because there was no first-line label for erlotinib in patients with EGFR mutations, even though that was our standard treatment for them. Having the first-line approval will allow us to proceed with further trials of erlotinib in combination with other agents to hopefully delay resistance.
As for the companion diagnostic test, there are many ways of testing for the EGFR mutations. They have approved just this one assay, but I am assuming that — because many academic centers have in-house testing for these mutations, and because there are many companies that already have similar tests — it is likely any positive test result for an EGFR exon19 deletion or an exon 21 L858R mutation will be sufficient.
Click Here to Manage Email Alerts