Gefitinib gets US approval for non-small cell lung cancer

20 Jul 2015

The US Food and Drug Administration has approved gefitib for the treatment of patients with metastatic non-small cell lung cancer (NSCLC). The eligible patients for the new drug are those whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test.

This approval of gefitinib is being approved concurrently with a labeling expansion of the therascreen EGFR RGQ PCR Kit, a companion diagnostic test for patient selection.

Clinical design of the approval-related study

The approval of gefitinib was based on the results of a multicentre, single-arm, open-label clinical study of a total of 106 treatment naïve-patients (patients with no treatment history) for with metastatic EGFR mutation positive NSCLC who received gefitinib at a dose of 250 mg daily until disease progression or intolerable toxicity.

Patients were randomized (1:1) to receive gefitinib 250 mg once daily or up to 6 cycles of carboplatin/paclitaxel. The subset population consisted of 186 of 1217 patients (15%) determined to be EGFR positive and had radiographic scans available for a retrospective assessment by a BICR.

In this subset, there were 88 gefitinib-treated patients and 98 carboplatin/paclitaxel-treated patients.

Clinical results of the study

The major efficacy outcome was objective response rate (ORR) according to RECIST v1.1 as evaluated by both a Blinded Independent Central Review (BICR) and investigators.

The BICR ORR was 50% with a median duration of response of 6.0 months.Investigator-determined ORR was 70% with a median duration of response of 8.3 months. Efficacy results were supported by an exploratory analysis of a subset of a randomized, multicentre, open-label trial conducted in patients with metastatic adenocarcinoma histology NSCLC receiving first-line treatment.

In addition,

  • The BICR ORR was 67% with duration of response of 9.6 months for gefitinib-treated patients and
  • 41% with duration of response of 5.5 months for carboplatin/paclitaxel-treated patients.


Clinical trial evaluating the safety data for adverse events

Safety data was evaluated for common adverse reactions in a double-blind placebo- controlled trial of 1692 patients.

Of the 1129 patients who received gefitinib, the most common (greater than or equal to 20%) adverse reactions in order of decreasing frequency were:

  • Skin reactions,
  • aspartate aminotransferase (AST) increased,
  • alanine aminotransferase (ALT) increased,
  • proteinuria and diarrhea.

The most common (greater than or equal to 2%) grade 3-4 adverse reactions were:

  • Proteinuria,
  • Diarrhea,
  • ALT increased,
  • Decreased appetite,
  • AST increased and skin reactions.

Approximately 5% of gefitinib-treated patients discontinued treatment due to an adverse reaction.

What about the serious and uncommon adverse events?

Serious and uncommon adverse drug reactions were evaluated in 2462 patients with NSCLC who received gefitinib monotherapy in three randomized clinical studies.

Significant adverse reactions were interstitial lung disease, which occurred in 1.3% of patients, fatal hepatotoxicity which occurred in 0.04% of patients, and grade 3 ocular disorders which occurred in 0.1% of patients.

The recommended dose of gefitinib is 250 mg orally once daily with or without food.

Treatment should continue until disease progression or unacceptable toxicity.

Source: eCancer News
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