Jul 25, 2014
At the 2014 ASCO Annual Meeting, Pasi A. Jänne, MD, PhD, of the Dana-Farber Cancer Institute and Harvard Medical School, presented findings from a phase I study of a new epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), AZD9291, selective for activating and resistance mutations, which offers a promising new treatment option for patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC) that is resistant to standard EGFR inhibitors. Approximately 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.
EGFR mutations were discovered in a subset of patients with lung cancer 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 and afatinib, and additional therapies are needed.
Importantly, AZD9291 selectively targets mutant EGFR in tumors and appears to cause fewer skin toxicities than approved EGFR TKIs. While existing drugs block both the mutant EGFR in the tumor and the normal EGFR in the skin and other organs, which often leads 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.”
Dr. Jänne received a 2001 Young Investigator Award (YIA) from the Conquer Cancer Foundation early in his career, to examine whether selective and non-selective cyclooxygenase-2 (COX-2) inhibitors can preventor delay the development of lung adenocarcinomas in a genetic murine model. “The YIA got me interested in studying lung cancer,” 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 clinically. In addition to his own research, Dr. Jänne is also a mentor to several promising physician-scientists who have received Conquer Cancer Foundation grants themselves, including Geoffrey Oxnard, MD (2010 YIA, 2012 Career Development Award [CDA]), and Curtis Chong, MD (2013 YIA).
Dr. Jänne recently served as Chair of the 2013-2014 Conquer Cancer Foundation Grants Selection Committee, which reviews YIA and CDA applications. He has also served on the Journal of Clinical Oncology Editorial Board, as well as the ASCO Cancer Education and Scientific Program Committees.
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.”
Dr. Jänne is a professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School. He has been an ASCO member since 1999.
Conquer Cancer Foundation Grant Recipients Present Research Advances at 2014 ASCO Annual Meeting, Three Featured In Press Program
More than 200 current and former Conquer Cancer Foundation grant recipients presented their research at the 2014 ASCO Annual Meeting. Three of the studies highlighted in the official ASCO Annual Meeting press program were led by CCF past grant recipients: Dr. Jänne (lung cancer), Joyce F. Liu, MD, MPH (ovarian cancer), and Antoni Ribas, MD, PhD (melanoma).
Dr. Liu’s research demonstrated that a combination of the PARP inhibitor olaparib and the antiangiogenic drug cediranib delays recurrent ovarian cancer progression by more than eight months compared with olaparibalone. She received a Young Investigator Award in 2008. Dr. Ribas’ study concluded that that the PD-1 targeting antibody MK-3475 yields long-term responses in a high percentage of patients with advanced melanoma. He received a Career Development Award in 2000.
Visit conquercancerfoundation.org to read more about the investigations conducted by Dr. Jänne, Dr. Liu, and Dr. Ribas.