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ELCC 2017: Osimertinib Improves Symptoms in Advanced Lung Cancer

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Key Points

  • Osimertinib significantly reduced many lung cancer symptoms, primarily appetite loss, fatigue, breathlessness, and chest pain.
  • Compared to chemotherapy, osimertinib also significantly improved global health status, physical functioning, role functioning, and social functioning scores.
  • Results showed a nonsignificant trend for reduced cough and improved emotional and cognitive function on osimertinib.

Osimertinib (Tagrisso) improved cancer-related symptoms in patients with advanced lung cancer, according to an analysis of patient-reported outcomes from the AURA3 phase III clinical trial presented by Lee et al at the 2017 European Lung Cancer Conference (ELCC, Abstract 85O).

“With my past experience conducting clinical trials, I often see new treatments that might be more effective, but are also usually more toxic,” said lead author Chee Lee, MD, Medical Oncologist, St George Hospital Cancer Care Centre, New South Wales, Australia. “Osimertinib not only increases progression-free survival, but it is well-tolerated, which makes a big difference for our patients.”

AURA3 Trial

AURA3 included 419 patients with advanced epidermal growth factor receptor (EGFR) mutation–positive non­–small cell lung cancer (NSCLC) who had disease progression after first-line EGFR tyrosine kinase inhibitor therapy. They were randomly assigned to receive the oral tyrosine kinase inhibitor osimertinib or chemotherapy.

Patients taking osimertinib had a significantly longer progression-free survival of 10.1 months vs 4.4 months in those on chemotherapy (hazard ratio = 0.30; 95% confidence interval = 0.23–0.41; P < .001), according to results of the trial published by Mok et al in The New England Journal of Medicine.

Patient-Reported Outcomes of AURA3

Information was collected using two standardized European Organisation for Research and Treatment of Cancer (EORTC) questionnaires: the supplemental 13-item lung cancer module (QLQ-LC13), which assessed lung cancer–specific symptoms, and the 30-item core quality-of-life questionnaire for global health status (QLQ-C30), which assessed general cancer symptoms. Patients completed both questionnaires at baseline and then at regular intervals until disease progression and beyond. The researchers then analyzed the findings to see if symptom control was better with osimertinib or chemotherapy.

The researchers found that osimertinib significantly reduced many lung cancer symptoms—primarily appetite loss, fatigue, breathlessness, and chest pain. There was a trend for osimertinib to reduce cough, but it was not statistically significant. Dr. Lee said, “It generally took longer for these symptoms to get worse in patients taking the osimertinib tablet compared to chemotherapy.” In patients who had symptoms at the start of the study, appetite loss improved significantly faster on osimertinib compared to chemotherapy, and patients became less fatigued and less breathless.

Compared to chemotherapy, osimertinib also significantly improved global health status, physical functioning, role functioning, and social functioning scores. There was a trend toward improved emotional and cognitive function with osimertinib, but it was not statistically significant.

“Patients taking osimertinib were [better able] to do normal daily activities and socialize than those on chemotherapy,” said Dr. Lee.

He continued, “Patients with metastatic lung cancer receiving first-line treatment are really quite sick. Patients in the AURA3 trial had disease progression on first-line treatment and were receiving second-line therapy, so they were even sicker. To be able to reduce cancer symptoms and improve quality of life in addition to progression-free survival for these patients is a major leap.”

Dr. Lee concluded: “For patients with incurable cancer, prolonging only progression-free survival probably has very little meaning for them. However, treatment that can additionally improve symptoms and maintain quality of life probably means a lot for these patients.”

Commentary

Commenting on the importance of the trial, Solange Peters, MD, PhD, Head of Medical Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, said, “The AURA3 trial has made it clear that when patients have disease progression on first-line targeted therapy for EGFR mutation–positive NSCLC with a T790M resistance mutation, they should stay on targeted therapy using a new generation inhibitor rather than switching to traditional chemotherapy for the second line of therapy. Patients taking second-line osimertinib had longer progression-free survival and less toxicity than those on chemotherapy.”

“We also have to keep in mind that osimertinib is only effective in the 55% of EGFR mutation–positive NSCLC patients whose resistance to a front-line [tyrosine kinase inhibitor] is caused by this T790M gatekeeper mutation,” she continued. “More research is needed to find better second-line treatments for patients with a different mechanism of resistance, for whom chemotherapy is currently the only option. Finally, the opportunity for front-line prescription of osimertinib in all EGFR-mutated NSCLC will be described by the FLAURA trial, which is comparing a first-generation [tyrosine kinase inhibitor] to osimertinib as the very initial treatment and should report later this year.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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