1. Goodwin, Peter M.

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GENEVA, Switzerland-A pooled analysis of the AURA P1 and AURA P2 studies-reported at the 2016 European Lung Cancer Conference-found a high overall response rate (ORR) in patients with treatment-resistant advanced lung cancer who received the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib, showing "encouraging" progression free survival (PFS) and "manageable" tolerability (Abstract LB A2).

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Lead author James Yang, MD, PhD, Director of the Departments of Oncology and Medical Research at the National Taiwan University Hospital in Taipei, said they had confirmed osimertinib is effective in pre-treated non-small cell lung cancer (NSCLC) tumors expressing the T790M mutation that have become resistant to first- or second-generation EGFR TKIs.


"We found a response rate and PFS that were consistent between the two studies and with earlier reports from the AURA studies," Yang explained. And he added that adverse events such as interstitial lung disease and QT prolongation were infrequent, with similar rates to previous analyses.


Methodology & Results

Yang told Oncology Times that his group typically detected T790M mutation on re-biopsy in 50 to 60 percent of patients with NSCLC who had progressed on previous EGFR TKI therapy. And he said the pooled analysis was conducted to study the treatment efficacy of osimertinib in these patients.


"In the phase I cohort we had 63 patients. The response rate was 71 percent and the duration of response was 9.7 months," he said. And he added that in the phase II combined cohort with 411 patients the response rate was 66 percent and median duration of response was 12.5 months. The study reported PFS of 9.7 months for the phase I cohort and 11 months for the phase II cohort.


Patients with the mutation who had progressed following EGFR-TKI therapy received osimertinib 80 mg once daily. T790M-positive status was confirmed by central testing of biopsy samples. All patients had measurable disease, WHO performance status 0 to 1 and acceptable organ function. Those with stable brain metastases were also included. The most common adverse events (AEs) were rash and diarrhea.


Impact on Practice

Osimertinib is described as a potent, oral, irreversible EGFR-TKI that is effective in patients with EGFR T790M mutation-positive advanced NSCLC and recently received accelerated approval for this setting in the U.S., EU and Japan.


Due to the high response rate and long duration of response noted in their findings Yang regarded osimertinib as the only choice in resistant cancers that had the mutation. "This will change the whole second line treatment in the future," he said.


He noted that in this mature pooled analysis that PFS was long compared to the 4 to 5 months provided by chemotherapy. "This is good news for patients with EGFR mutations who have failed EGFR TKI, for whom osimertinib is now standard of care," he said, adding that molecular diagnosis for T790M should now be adopted routinely.


And addressing cancer doctors directly Yang said that every patient who has progressed on first-generation EGFR TKI should be encouraged to think about this drug. "If this is available, get a biopsy and prove that this patient has T790M mutation and you should try to use this drug for your patient," he noted.


Commenting on the results, Enriqueta Felip, MD, a medical oncologist at Vall d'Hebron University Hospital in Barcelona, Spain said the study confirmed the good results previously reported with osimertinib in this setting. "Nowadays, in patients with EGFR mutation who progress after an EGFR TKI, there is a clear need for T790M testing since we now have a highly active agent, osimertinib, for this situation," she emphasized.


Additionally, Tony Mok, MD, Professor of Thoracic Oncology at The Chinese University of Hong Kong, said the case for using osimertinib encouraged the use of liquid biopsies to assay T790M mutation status non-invasively. His group reported that 60 percent of patients with T790M positive NSCLC could have avoided an invasive biopsy by use of a plasma test.


Wilfried Eberhardt, MD, a medical oncologist at the West German Cancer Center in University Hospital Essen University Duisburg-Essen and International Association for the Study of Lung Cancer (IASLC) Scientific Committee Chair, who was not involved in the study, told Oncology Times that it was now correct to start off with a first or second generation TKI and if there was progression to switch to osimertinib which he regarded as tolerable. "The toxicity profile of osimertinib is even less than the first generation TKI's," he concluded, noting that it also seems to be effective in first line.


Peter M. Goodwin is a contributing writer.