Clinical Implications of the T790M Mutation in Disease Characteristics and Treatment Response in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Non–Small-Cell Lung Cancer (NSCLC)

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Abstract

Background

The secondary T790M mutation accounts for more than 50% of acquired tyrosine kinase inhibitor (TKI) resistance in patients with EGFR-mutated non–small-cell lung cancer (NSCLC). Recent reports suggest this resistance mutation may be more common among patients with longer progression-free survival (PFS) on first-line TKI therapy, but much is still unknown.

Materials and Methods

Our group collected medical records from patients who underwent a biopsy for T790M mutation testing while screening for clinical trials involving the drug rociletinib (CO-1686), a T790M mutation–specific TKI. Medical records were retrospectively analyzed for demographic data, PFS, and best response to previous therapies.

Results

Our patient cohort included 69 T790M+ patients and 28 T790M− patients. Patients who later developed a T790M mutation had a longer PFS on first-line TKI therapy (12.0 vs. 9.0 months, P = .021), but overall response rate (ORR) was the same (75.0% vs. 81.0%, P = .76). There was no difference in PFS on TKI rechallenge (4.0 vs. 3.0 months, P = .94), although there was a trend toward higher ORR in T790M+ patients (22.2% vs. 0%, P = .12). T790M+ patients had a longer PFS on initial chemotherapy treatment (5.0 vs. 4.0 months, P = .025) and a trend toward higher ORR (40.0% vs. 21.4%, P = .31).

Conclusion

Our study confirms that tumors expressing T790M have a more indolent progression of disease compared with their T790M− counterparts when treated with both first-line TKI and cytotoxic chemotherapy.

Micro-Abstract

We characterized differences in the natural history of patients with EGFR-mutated NSCLC whose tumors develop a T790M resistance mutation compared with those whose tumors do not. We found T790M+ patients had a longer PFS with first-line TKI and chemotherapy, but no difference with TKI rechallenge. Response rate was similar for all therapies evaluated, even when differences in PFS were seen.

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