Osimertinib plus chemotherapy tolerable in EGFR-mutated NSCLC

CHICAGO — Concurrent treatment with osimertinib and standard chemotherapy did not significantly increase toxicities among patients with metastatic, EGFR-mutated non-small cell lung cancer, according to findings of a retrospective analysis presented at the ASCO Annual Meeting.

Joel W. Neal, MD, PhD, assistant professor of medicine at the Stanford University Medical Center, and colleagues reported that this treatment combination could particularly benefit patients with central nervous system (CNS) metastases, given osimertinib’s (Tagrisso, AstraZeneca) “excellent CNS penetration.”

Current data suggest that first-generation EGFR tyrosine kinase inhibitors erlotinib (Tarceva; Genentech, Astellas Oncology) and gefitinib (Iressa, AstraZeneca) are well tolerated when they are combined with standard chemotherapy, according to the researchers. However, results from the IMPRESS trial did not demonstrate a clinical benefit of continuing gefitinib with chemotherapy after disease progression.

Although less is known about the safety and efficacy of adding the third-generation EGFR TKI osimertinib to chemotherapy, Neal and colleagues hypothesized that osimertinib’s “unique feature” of CNS activity could improve CNS and overall outcomes.

To test their theory, the researchers assessed the outcomes of 44 patients with metastatic EGFR-mutated NSCLC who received osimertinib plus chemotherapy as second-line or later therapy. Most patients (86%) in the analysis had baseline CNS metastases. Prior treatment before osimertinib plus chemotherapy included osimertinib alone (98%), an EGFR TKI other than osimertinib (93%), chemotherapy alone (34%) and immunotherapy (7%).

Combinations of chemotherapy plus osimertinib varied. Osimertinib was given at 80 mg daily, 160 mg daily or 80 mg every other day. Twenty-eight patients received platinum-doublet chemotherapy, including carboplatin plus pemetrexed (n = 24); platinum, pemetrexed and bevacizumab (n = 2); and carboplatin plus taxane (n = 2). Twenty-nine patients received single-agent chemotherapy, including gemcitabine (n = 9), pemetrexed (n = 6), docetaxel (n = 5), irinotecan (n = 3), vinorelbine (n = 2), nab-paclitaxel (n = 2), pemetrexed plus bevacizumab (Avastin, Genentech; n = 1) and docetaxel-ramucirumab (Cyramza, Eli Lilly; n = 1).

Results of a safety analysis showed the combination of chemotherapy plus osimertinib did not significantly increase toxicities, according to the researchers. However, they noted that rates of thrombocytopenia (59%, any grade) and neutropenia (31%, any grade) “may be higher than historical chemotherapy controls.”

Chemotherapy was delayed or reduced in eight patients (18%) due to fatigue (n = 5), transaminitis (n = 1), neutropenia (n = 1) or thrombocytopenia (n = 1). Osimertinib was reduced in one patient for fatigue and another patient for transaminitis. One patient discontinued osimertinib due to reduced cardiac ejection fraction.

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The median duration of treatment was 5.3 months (95% CI, 3.6-8) in the overall population, 6.1 months (95% CI, 4.1 to not reached) among patients who received platinum-doublet chemotherapy and 3 months (95% CI, 1.8-4.8) among those who received single-agent chemotherapy. The findings for platinum-doublet and single-agent chemotherapy are comparable to historical controls, according to the researchers.

Median OS was 48.4 months (95% CI, 37.2-54.4) from metastatic disease diagnosis and 20.4 months (95% CI, 17.6-32) from osimertinib treatment initiation.

The researchers further reported that osimertinib was associated with “favorable” CNS control. Nine (24%) of the 38 patients with brain metastases had CNS disease progression; however, only two patients (5%) were treated with radiation at progression.

“Despite IMPRESS, first-line EGFR TKI and [chemotherapy] appears promising,” Neal and colleagues concluded. “A prospective study of osimertinib [plus] chemotherapy for [EGFR-mutated] NSCLC with brain metastases is planned (PROTECT).” – by Stephanie Viguers

Reference:

Neal JW, et al. Abstract 9083. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.

Disclosure: Neal reports serving in consulting or advisory roles for ARIAD/Takeda, AstraZeneca, Eli Lilly and Company, Exelixis, Genentech/Roche, Jounce Therapeutics and Loxo Oncology and receiving research funding on behalf of his institution from ARIAD/Takeda, Boehringer Ingelheim, Exelixis, Genentech/Roche, Merck, Nektar and Novartis. Please see the abstract for all other authors’ relevant financial disclosures.