Lung and other thoracic tumours/ Anticancer agents & Biologic therapy
GENEVA, Switzerland – The third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib is effective in the first-line treatment of EGFR mutated non-small-cell lung cancer (NSCLC), according to a late-breaking abstract presented at the European Lung Cancer Conference (ELCC) 2016 in Geneva, Switzerland.1 A second late-breaking abstract confirms the drug’s effectiveness in patients with the T790M mutation.
EGFR inhibition is the standard of care for NSCLC patients with EGFR activating mutations but nearly 50 to 60% develop resistance by developing a T790M mutation. Osimertinib is a potent inhibitor of the original EGFR mutations (exon 19 and exon 21) and the T790M. The study presented was investigated whether the use of Osimertinib as first-line therapy for EGFR mutation positive NSCLC would result in favorable efficacy due to delayed T790M mediated resistance.
Studies on OSIMERTINIB as First-line treatment:
The study was conducted on 60 patients from two phase I expansion cohorts of the AURA trial that had locally advanced or metastatic EGFR mutated NSCLC. Thirty patients received 80 mg a day and 30 received 160 mg a day in the first-line setting. The median follow-up was 16.6 months.
The overall response rate was 77%. Median progression free survival (PFS) was 19.3 months for the 160 mg dose and has not yet been reached for the 80 mg dose. The drug was well tolerated with few adverse events, particularly at the approved 80 mg dose, where just 10% of patients required dose reduction to manage toxicities.
Prof Suresh Ramalingam, professor of haematology and medical oncology at Emory School of Medicine and deputy director of Winship Cancer Institute, Atlanta, Georgia, US, study author, said: “The overall response rate was among the best reported for first-line therapy of EGFR mutated NSCLC. The PFS results are exciting, well exceeding the historical control rates of 10 to 13 months with first or second generation drugs. Many of the patients have not had disease progression on the study and are still benefitting from treatment.”
Initial data suggests that patients who had disease progression did not have T790M mutation as the mechanism of resistance. “That tells us that we may be changing the biology of the disease with the use of first-line osimertinib,” said Ramalingam.
Further investigations will be conducted in a phase III trial comparing Osimertinib with other EGFR TKIs, Erlotinib or gefitinib for front line therapy.
Dr Enriqueta Felip, a medical oncologist at Vall d`Hebron University Hospital in Barcelona, Spain, not involved in the study, said: “The results with osimertinib in the first-line look promising. The ongoing randomised trial will define the role of osimertinib in the treatment of EGFR mutated patients who are treatment-naive.”
REDUCED ADVERSE REACTIONS:
Prof James Yang, director of the Department of Oncology and Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan has said “We found a response rate and PFS that were consistent between the two studies and with earlier reports from the AURA studies. Adverse events such as interstitial lung disease and QT prolongation2 were infrequent, with similar rates to our previous analyses.”
- LBA1_PR: Osimertinib as first-line treatment for EGFR mutation-positive advanced NSCLC: updated efficacy and safety results from two Phase I expansion cohorts. S. Ramalingam, US. Thursday 14th April 2016 – 15:30-15:45 New strategies for EGFR addicted NSCLC Room B\
- LBA2_PR: Osimertinib (AZD9291) in pre-treated pts with T790M-positive advanced NSCLC: updated Phase 1 (P1) and pooled Phase 2 (P2) results. J. Yang, Taiwan. Thursday 14th April 2016 – 15:45-16:00 New strategies for EGFR addicted NSCLC Room B
- The QT interval is a measure of the electrical cycle of the heart. A prolonged QT interval indicates a risk of abnormal heart rhythms.