New FDA approved treatment for non-small cell lung cancer

New FDA approved treatment for non-small cell lung cancer

13 Nov 2015

The US Food and Drug Administration has granted accelerated approval to AstraZeneca’s osimertinib (Tagrisso) once daily tablets. The drug will be used for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, who have progressed on or after epidermal growth factor receptor tyrosine kinase inhibitor (TKI) therapy.

The approval was based on two multicenter, single-arm, open-label clinical trials in patients with metastatic epidermal growth factor receptor T790M mutation-positive non-small cell lung cancer who had progressed on prior systemic therapy, including an epidermal growth factor receptor tyrosine kinase inhibitor (Study 1 and 2).

Ongoing responses for the majority of study participants

All patients were required to have epidermal growth factor receptor T790M mutation-positive non-small cell lung cancer as detected by the cobas EGFR mutation test and received osimertinib 80 mg once daily. The major efficacy outcome measure was objective response rate (ORR). Duration of response (DOR) was an additional outcome measure. In particular, according to the researchers’ report:

• Study 1 (n=201) showed an objective response rate of 57%
• In Study 2 (n=210) the objective response rate was 61%
• The majority (96%) of patients in both trials had ongoing responses at the time of primary analysis
• The median duration of response had not been reached with duration of ongoing responses ranging from 1.1 to 5.6 months after a median duration of follow-up of 4.2 months (Study 1) and 4.0 months (Study 2).
• The dose finding phase of Study 1 (n=63) showed an objective response rate of 51% and median duration of response of 12.4 months.

Adverse events leading to dose reductions and discontinuation of the study

Safety data was evaluated in 411 patients who received osimertinib at a dose of 80 mg daily. The most common adverse events (grade 1-2) were diarrhea (42%), rash (41%), dry skin (31%), nail toxicity (25%), eye disorders (18%), nausea (17%), decreased appetite (16%), and constipation (15%).  The most common Grade 3-4 adverse reactions were pneumonia and pulmonary embolism (2% each).The most common nonfatal serious adverse events (SAEs) included pneumonia and pulmonary embolus.

In addition, dose reductions due to adverse events occurred in 4.4% of patients. The most frequent adverse reaction leading to dose reductions or interruptions were prolonged QTc and neutropenia (2% each). On the other hand, adverse events leading to discontinuation included ILD/pneumonitis (2%), and cerebrovascular accident (1%). Fatal adverse events occurred in 3.2% of patients, including 4 cases of pneumonitis attributed to osimertinib.

The recommended dose and schedule for osimertinib is 80 mg given orally once daily. Osimertinib received Breakthrough Therapy Designation and the current indication was approved under FDA’s accelerated approval programme.

Source: eCancer News