LUGANO-MADRID, 9 September, 2017 - Osimertinib improves progression-free survival by 54% compared to standard first line therapy in patients with EGFR mutated non-small-cell lung cancer (NSCLC), according to late-breaking results from the FLAURA trial presented today at the ESMO 2017 Congress in Madrid. (1)
EGFR mutations are present in around 15% of NSCLC in Western populations, rising to 35% in Asian populations. EGFR inhibitors are superior to chemotherapy in the first line treatment of these patients. However, despite high response rates and good progression-free survival, patients invariably develop resistance to drugs such as erlotinib and gefitinib. In the majority of patients this resistance is mediated by a T790M mutation.
"We hypothesised that a drug which targets EGFR sensitising mutations and the T790M resistance mutation would be associated with a better outcome," said principal investigator Professor Suresh Ramalingam, MD, Deputy Director, Winship Cancer Institute of Emory University, Atlanta, Georgia, US.
Osimertinib is a third generation EGFR-tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR and T790M resistance mutations. A preliminary study in 60 treatment naive patients with EGFR mutations found that the median progression-free survival with osimertinib was 20.5 months, which was almost two-fold higher than results achieved with erlotinib or gefitinib.
FLAURA was a randomised phase III clinical trial comparing osimertinib to standard of care erlotinib or gefitinib as first line therapy in NSCLC patients with EGFR exon 19 or 21 mutations. The primary endpoint was progression-free survival. A total of 556 patients from Asia, Europe, and North America were randomised 1:1 to treatment with osimertinib or standard of care.
The median progression-free survival was 18.9 months with osimertinib compared to 10.2 months for the standard therapy, with a hazard ratio of 0.46 (95% confidence interval, 0.37-0.57; p<0.0001). The benefit in progression-free survival was consistent across all subgroups, including patients with and without brain metastases at the start of the study.
The median duration of response was two-fold higher for patients treated with osimertinib (17.2 months) versus standard of care (8.5 months). The overall response rate was 80% with osimertinib compared to 76% with standard of care treatment.
Overall survival appeared to favour osimertinib with a hazard ratio of 0.63 although this was not statistically significant at the interim overall survival analysis (25% maturity). (2) Median overall survival was not reached. The incidence of grade 3 or higher toxicities was lower for osimertinib (34%) than the standard treatment (45%).
Ramalingam said: "Osimertinib was clearly superior to standard first line treatment in patients with EGFR mutated NSCLC. The progression-free survival benefit for patients with and without brain metastases was almost identical, suggesting that osimertinib is active in the brain as well as in systemic sites. This is important because brain metastasis is a common problem in EGFR mutated patients."
Regarding toxicities, Ramalingam said: "The safety profile of osimertinib was more favourable despite longer treatment duration (16.2 months) compared to standard of care (11.5 months)."
Commenting on the results for ESMO, Dr Enriqueta Felip, Head, Thoracic and H&N Cancer Group, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain, said: "Osimertinib reduced the risk of cancer progression by 54% compared with standard of care and extended the median time to progression by about nine months. The drug was well tolerated and it has activity in the brain. Based on these results, osimertinib should be considered a new first line treatment option for patients with EGFR mutations."
"Overall survival data is not yet mature and there is a clear need to continue follow-up to see if those treated with osimertinib live longer," she added.
Regarding the need for further research, Felip said: "More data is needed on the mechanisms of acquired resistance in patients treated with osimertinib in the first line setting."
Notes to Editors
Please make sure to use the official name of the meeting in your reports: ESMO 2017 Congress
1 Abstract LBA2_PR 'Osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) with EGFRm advanced NSCLC: FLAURA' will be presented by Dr Suresh Ramalingam during Presidential Symposium I on Saturday 9 September 2017, 16:30 to 18:00 (CEST) in the Madrid Auditorium.
2 The p value for overall survival (OS) was p=0.0068. This was not statistically significant because a p value of 0.0015 was required for statistical significance at the current OS maturity.
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