Although it is still a bit early, our study suggests that AZD9291 may offer an effective new therapy option for [patients with treatment-resistant NSCLC], without the skin side effects we typically see with existing EGFR inhibitors.
—Pasi Jänne, MD, PhD
At the 2014 ASCO Annual Meeting, Pasi Jänne, MD, PhD, Professor of Medicine at Dana-Farber Cancer Institute and Harvard Medical School, presented findings from a phase I study of AZD9291, a new mutant-selective EGFR tyrosine kinase inhibitor that offers a promising new treatment option for patients with advanced, EGFR-mutant, non–small cell lung cancer that is resistant to standard EGFR inhibitors. Roughly 50% of patients experienced tumor shrinkage, and the drug worked particularly well in patients with the T790M mutation (detected in 60% of patients), which causes the most common form of EGFR therapy resistance.
Targeting EGFR-Mutant Lung Cancer
EGFR mutations were discovered in a subset of lung cancer patients in 2004, and since then several clinical trials have shown that for patients who are newly diagnosed with advanced lung cancer and have an EGFR mutation, initial therapy with an EGFR inhibitor is better than conventional chemotherapy. Unfortunately, all patients ultimately develop resistance to current generation EGFR inhibitors, such as erlotinib (Tarceva) and afatinib (Gilotrif), and additional therapies are needed.
Importantly, AZD9291 (a drug manufactured by AstraZeneca) selectively targets mutant EGFR in tumors and appears to cause fewer skin toxicities than approved EGFR tyrosine kinase inhibitors. While existing drugs block both the mutant EGFR in the tumor and the normal EGFR in the skin and other organs, often leading to debilitating skin rash or acne, AZD9291 acts mostly on the mutant EGFR in a patient’s tumor.
“There is currently no standard treatment for patients with lung cancer who experience disease progression after initial therapy with an EGFR kinase inhibitor,” said Dr. Jänne. “Although it is still a bit early, our study suggests that AZD9291 may offer an effective new therapy option for these patients, specifically in those with the T790M resistance mechanism, without the skin side effects we typically see with existing EGFR inhibitors.”
Conquer Cancer Foundation Grants
Dr. Jänne received a 2001 Young Investigator Award (YIA) from the Conquer Cancer Foundation early in his career to examine whether selective and nonselective cyclooxygenase-2 (COX-2) inhibitors can prevent or delay the development of lung adenocarcinomas in a genetic murine model. “The YIA got me interested in studying lung cancer to begin with,” said Dr. Jänne. “During my fellowship, I knew I was going to do lung cancer research, but receiving the YIA gave me extra encouragement and motivation that this was the right track moving forward.”
Part of the team that originally discovered the EGFR mutation in 2004, Dr. Jänne has spent the past 10 years studying EGFR-mutant lung cancer, trying to understand drug resistance and develop therapies, both preclinically and now clinically. In addition to his own research, Dr. Jänne is also a mentor to several promising physician scientists who have successfully received Conquer Cancer Foundation grants themselves, including Geoffrey Oxnard, MD (2010 YIA, 2012 CDA) and Curtis Chong, MD (2013 YIA). He recently chaired the 2013–2014 Conquer Cancer Foundation Grants Selection Committee, which reviews YIA and CDA applications, and has also served on the Journal of Clinical Oncology Editorial Board, ASCO Cancer Education Committee, and ASCO Scientific Program Committee.
The Conquer Cancer Foundation believes that it is important to invest in early-career researchers, like Dr. Jänne, because that is how the treatments of tomorrow are born. As Dr. Jänne explains, “Donating to the Conquer Cancer Foundation helps support very important early career grants. It is incredibly important to support people early in their research career because that is ultimately how we make advances in cancer.”
Help the Conquer Cancer Foundation accelerate breakthroughs, launch careers, and improve cancer care by donating today at www.conquercancerfoundation.org/donate. ■
© 2014. American Society of Clinical Oncology. All rights reserved.