Diagnosis of adenocarcinoma of the lung, a major subtype of non-small lung cancer (NSCLC), nowadays triggers mandatory testing of tumor tissue for alterations in four genes: EGFR, ALK, ROS1, and more recently, BRAF. If present, these alterations predict sensitivity to specific targeted drugs approved by the U.S. Food and Drug Administration (FDA) that work better and often longer than standard chemotherapy, and are better tolerated.
However, there are many more targetable/actionable genomic alterations (also known as “drivers”) in NSCLC. This blog post will briefly discuss most of them, with the goal of promoting molecular testing for more than the four “usual suspects” mentioned above. Some patients with these alterations may benefit from FDA-approved drugs or from enrollment in clinical trials that are testing additional drugs and drug combinations. Continue reading…
“New results again demonstrated the benefit of frontline osimertinib (Tagrisso) in patients with EGFR-positive advanced non–small cell lung cancer (NSCLC) and CNS metastases at baseline, according to data presented at the 2017 ESMO Asia Congress.
“The subgroup analysis from the phase III FLAURA trial included 128 patients with at least 1 measurable and/or nonmeasurable CNS lesion at baseline. Among 61 patients who received osimertinib, the CNS objective response rate (ORR) was 66%, compared to 43% (odds ratio, 2.5; 95% CI 1.2-5.2; P = .011) in 67 patients who received standard EGFR TKI therapy with erlotinib (Tarceva) or gefitinib (Iressa).”
“The European Society for Medical Oncology (ESMO) 2017 Congress is just around the corner, and we can already say with confidence that there will be many provocative presentations, including several that are poised to change practice. At this point, we can only rely on the abstracts and press releases for several of these, but here are my early impressions on the top five presentations in lung cancer for ESMO 2017.”
Medical guidelines for treatment of newly diagnosed non-small cell lung cancer (NSCLC) mandate upfront testing of tumor tissue for mutations in the EGFR gene (as well as ALK and ROS gene translocation). EGFR mutations are found in 10 to 15% of white patients, but in patients of East Asian origin such mutations are in encountered in approximately 48%. However, with new data and drugs entering the playing field, newly diagnosed patients’ treatment decisions could become more complex.
There is a good reason to test for EGFR mutations: the accumulated data show that, compared to first-line chemotherapy, treatment with drugs that inhibit the activity of EGFR in patients with activating EGFR mutations improves patients’ median progression-free survival (PFS) time from 4.6 to 6.9 months to 9.6 to 13.1 months, and has a higher objective response rate (ORR). Moreover, EGFR inhibitors are associated with a significantly lower incidence of adverse effects and better control of disease symptoms. Continue reading…
“AstraZeneca today announced that the Phase III FLAURA trial showed a statistically-significant and clinically-meaningful progression-free survival (PFS) benefit with Tagrisso (osimertinib) compared to current 1st-line standard-of-care treatment (erlotinib or gefitinib) in previously-untreated patients with locally-advanced or metastatic epidermal growth factor receptor mutation-positive (EGFRm) non-small cell lung cancer (NSCLC).
“Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: ‘The strong results from the FLAURA trial are very exciting news for patients with EGFR mutation-positive non-small cell lung cancer, providing physicians with a potential new first-line treatment option to improve outcomes in this disease. We will now initiate discussions with global health authorities on the data and regulatory submissions.’ ”
“Genprex, Inc. today announced positive interim data from an ongoing Phase II clinical trial (NCT01455389) evaluating its investigational immunogene therapy candidate Oncoprex™ in combination with the tyrosine kinase inhibitor (TKI) erlotinib (Tarceva®) for the treatment of late stage non-small cell lung cancer (NSCLC) patients.”
“Treatment with the multikinase inhibitor cabozantinib (Cabometyx) alone or with erlotinib (Tarceva) improved progression-free survival vs erlotinib alone in second- or third-line treatment of advanced nonsquamous epidermal growth factor receptor (EGFR) wild-type non–small cell lung cancer (NSCLC), according to the phase II ECOG-ACRIN 1512 trial reported by Neal et al in The Lancet Oncology.”
“Targeted therapies that do not contain erlotinib can be beneficial for patients with KRAS-mutated (KRAS mut+) advanced non-small-cell lung cancer (NSCLC), according to a study published online Aug. 1 in the Journal of Clinical Oncology.
“Vassiliki Papadimitrakopoulou, M.D., from the University of Texas MD Anderson Cancer Center in Houston, and colleagues examined the effects of targeted therapies in NSCLC. Patients were randomized to four arms: erlotinib (22 patients), erlotinib plus MK-2206 (42 patients), MK-2206 plus AZD6244 (75 patients), or sorafenib (61 patients).
“The researchers found that the primary end point of an eight-week disease control rate (DCR) was 48 percent in all 186 evaluable patients (32, 50, 53, and 46 percent, respectively, for the four treatment arms). For the 27 percent of patients who were KRAS mut+, DCR was 20, 25, 62, and 44 percent, respectively, compared with 36, 57, 49, and 47 percent, respectively, for KRAS wild-type patients. Median progression-free survival was 2.0 months: 1.8 and 2.5 months for arms 1/2 and 3/4, respectively, in KRAS mut+ patients (P = 0.04). In KRAS wild-type patients, median overall survival was 6.5 months: 9.0 and 5.1 months in arms 1/2 and 3/4, respectively (P = 0.03).”
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This year, the Annual Meeting of the American Society of Clinical Oncology (ASCO) did not produce any truly groundbreaking revelations about new treatments for lung cancer. However, researchers did report quite a few positive findings, and some disappointing ones. I have summarized some of the more prominent presentations below. Continue reading…