Osimertinib treatment for patients with EGFR exon 20 mutation positive non-small cell lung cancer.

Epidermal growth factor receptor (EGFR) exon 20 insertions comprise 4-10 % of EGFR mutations in non-small cell lung cancer (NSCLC) and are associated with primary resistance to first and second generation EGFR tyrosine kinase inhibitors (TKIs). In vitro and preclinical animal studies have shown that osimertinib exerts antitumor activity against EGFR exon 20 mutation positive NSCLC. We report on a cohort of advanced stage NSCLC patients who harbor an EGFR exon 20 mutation and received osimertinib treatment. Twenty-one patients were treated with osimertinib 80 or 160 mg once daily from April 2016 to June 2018, in four institutions in the Netherlands. Data were obtained retrospectively. Progression free survival (PFS), disease control rate (DCR), overall survival (OS) and objective response rate (ORR) were assessed using RECIST v1.1. Thirteen patients received prior platinum-based chemotherapy, and three patients a first - or second generation EGFR TKI. We observed 1 partial response, 17 patients with stable disease and 3 with progressive disease as best response to osimertinib (ORR 5 %). Median PFS was 3.6 (95 % CI, 2.6-4.5) months. PFS did not differ for patients with co-occurring TP53 mutations (p = 0.937). The DCR at three months was 71 %. Median OS was 8.7 (95 % CI, 1.1-16.4) months. Osimertinib has limited antitumor activity in patients with EGFR exon 20 mutated NSCLC, with an ORR of 5 %.

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Declaration of Competing Interest Dr. de Langen reports grants from Boehringer, grants from AstraZeneca, non-financial support from Roche, grants and personal fees from Merck / MSD, grants and personal fees from BMS, outside the submitted work. Dr. Heideman is minority shareholder of Self-screen B.V., a spin-off company of VU University Medical Center (currently known as Amsterdam UMC, Vrije Universiteit Amsterdam). She has been on the speakers bureau of QIAGEN and serves occasionally on the scientific advisory boards of Pfizer and Bristol-Myers Squibb. Dr. Monkhorst reports grants from Roche, grants from MSD, grants from AstraZeneca, non-financial support from Roche, Takeda, Pfizer, and personal fees from MSD, personal fees from BMS, personal fees from Roche, personal fees from Abbvie, personal fees from AstraZeneca, personal fees from Diaceutics. Dr. van der Wekken reports grants from AstraZeneca, Boehringer-Ingelheim and Pfizer, Honorario for Advisory boards from AstraZeneca, Roche (Diagnostics), Bayer, Pfizer and Boehringer-Ingelheim, speakers’s fee from Pfizer, Roche, Boehringer-Ingelheim and AstraZeneca, all outside the submitted work and all transfered to UMCG. Dr Smit received fees for participation in advisory boards and speaking engagements as well as research support (all institutional) from AstraZeneca. Dr. Schuuring reports grants from Biocartis, BMS, Bio-Rad, Roche, Agena Bioscience, CC Diagnostics, Boehringer Ingelheim, honoria for advisory boards from AstraZeneca, Roche, Pfizer, Novartis, Bayer, BMS, BioCartis, Illumina, Agena Bioscience, CC Diagnostics, Janssen Cilag (Johnson&Johnson), Diaceutics, and speaker's fee from Bio-Rad, Abbott, Novartis, Roche, Biocartis, Illumina, Pfizer, Astrazeneca, all outside the submitted work and all transfered to UMCG account. The other authors have declared no conflicts of interest.