Molecular Diagnostics in NSCLC with David Berz, MD, PhD, and Philip Bonomi, MD - Episode 2
What are the therapeutic options for patients progressing after initial EGFR exon 19 TKI therapy?
BERZ:Although the frontline therapy for patients with exon 19 deletion, as well as driver mutations with an exon 21 epidermal growth factor receptor, are very active and provide us with a predictable response. Those response durations are unfortunately very limited and after somewhere between 10 and 12 months, most of those patients have progressed on those frontline therapies.
We have identified the resistance mechanism to those frontline therapies and the T790M mutation represents about 50- to-60% of all the secondary resistance events and, fortunately so, we have now developed second-line therapy and we have an FDA approved therapy for this very setting, osimertinib, which provides another response in about 50- to-60% of such patients.
BONOMI:This has really changed the playing field right now and has provided an opportunity for patients to have longer control of their disease with relatively well-tolerated therapy. In particular, the third-generation EGFR inhibitors are quite active against the T790M mutations. There is also some evidence that a second generation EGFR inhibitor plus an anti-EGFR antibody provides some benefit in this group of patients, and maybe those who are not T790M should be treated with that particular combination.
Naoko T. is a 74-year-old retired high school teacher originally from Nagoya, Japan. She currently lives in San Diego, California and enjoys tennis and traveling with her husband.
In November 2014, after several months of stable disease, the patient returns for follow-up visit with worsening back pain, and her CT scan is consistent with progression of metastatic lesions.
At this point, the patient declined further treatment, and by March 2015, she returned with worsening dyspnea and declining performance status