TKI Therapy After Disease Progression Not Recommended for Patients With EGFR+ NSCLC

10/04/17

Long-term data from a recent trial suggest that continuation of treatment with first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) beyond EGFR-positive non-small cell lung cancer (NSCLC) progression does not improve overall survival (OS).

Results of the trial were published in the Journal of Clinical Oncology (online October 2, 2017; doi:10.1002/JCO.2017.73.9250).

The recent Iressa Mutation-Positive Multicentre Treatment Beyond ProgRESsion Study (IMPRESS) compared the effects of continuation of gefitinib plus chemotherapy (cisplatin plus pemetrexed) with placebo plus chemotherapy in patients with EGFR-positive advanced NSCLC with progression after first-line gefitinib. Results from the IMPRESS study yielded no difference between treatments in regards to progression-free survival (PFS).

A group of international researchers conducted a follow-up study to provide final, mature, overall survival (OS) data from the previous IMPRESS trial. A total of 265 patients with NSCLC were randomly assigned to either treatment arm, and overall data maturity was reported at 66%.

Researchers also examined whether T790M mutation status had any association with treatment effect.

Results of the follow-up study showed that continuation of gefitinib plus chemotherapy was detrimental to OS compared with placebo plus chemotherapy (median OS, 13.4 months vs 19.5 months; HR, 1.44; 95% CI, 1.07-1.94; P = .016).

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Additionally, researchers reported that the detriment was statistically significant in patients exhibiting T790M-positive plasma samples (HR, 1.49; 95% CI, 1.02-2.21). On the contrary, statistical significance was not reached in T790M-negative patients (HR, 1.15; 95% CI, 0.68-1.94).

In their concluding remarks, researchers acknowledged that final OS data from IMPRESS are supportive of earlier PFS results. Furthermore, the data are “sufficient to warn physicians against the continuation of treatment with first-generation EGFR TKIs beyond radiologic disease progression when chemotherapy is initiated.” This treatment effect may be driven by T790M mutation-positive status, they wrote, but more research is warranted to validate such a relationship.—Zachary Bessette