High dose osimertinib in patients with advanced stage EGFR exon 20 mutation-positive NSCLC: Results from the phase 2 multicenter POSITION20 trial

Fenneke Zwierenga*, Bianca van Veggel, Lizza E.L. Hendriks, T. Jeroen N. Hiltermann, Birgitta I. Hiddinga, Lucie B.M. Hijmering Kappelle, Arja ter Elst, Sayed M.S. Hashemi, Anne Marie C. Dingemans, Cor van der Leest, Adrianus J. de Langen, Michel M. van den Heuvel, Anthonie J. van der Wekken

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Introduction: Patients with life-threatening advanced non-small cell lung cancer (NSCLC) who harbor an exon 20 deletion and/or insertion mutation (EGFRex20 + ) have limited effective treatment options. The high dose 3rd generation tyrosine kinase inhibitor (TKI) osimertinib shows promising in vitro activity in EGFRex20 + NSCLC tumors. Methods: The POSITION20 is a single arm phase II, multicenter study investigating 160 mg osimertinib in patients with EGFRex20+, T790M negative NSCLC. We allowed patients to be treatment naïve and to have asymptomatic brain metastases. The primary endpoint was overall response rate (ORR). Secondary outcomes were duration of response (DoR), progression free survival (PFS), overall survival (OS), and treatment related adverse events (trAEs). Results: From June 2018 to October 2021, 25 patients were enrolled across five centers in the Netherlands. The median age was 70 years (range, 47–87), 20 patients (80%) were women, and the median number of previous lines of therapy was 1 (range, 0–3). The exon 20 mutations were clustered between A763 and L777. The most common exon 20 mutations were p.(N771_H773dup) (n = 3) and p.(A767_V769dup) (n = 3). The ORR was 28% (95% CI, 12–49%), including seven partial responses, with a median DoR of 5.3 months (range, 2.7–27.6). The median PFS was 6.8 months (95% CI, 4.6–9.1) and the median OS was 15.2 months (95% CI, 14.3–16.0). The most common trAEs were diarrhea (72%), dry skin (44%), and fatigue (44%). The primary reason for discontinuation was progressive disease in 14 patients (56%). Conclusion: The POSITION20 study showed modest antitumor activity in patients with EGFRex20 + NSCLC treated with 160 mg osimertinib, with a confirmed ORR of 28% and acceptable toxicity.

Original languageEnglish
Pages (from-to)133-140
Number of pages8
JournalLung Cancer
Volume170
DOIs
Publication statusPublished - 1 Aug 2022

Bibliographical note

Funding Information:
FZ has no conflict of interest; BV has no conflict of interest; LLH reports research funding: Roche Genentech, Boehringer Ingelheim, AstraZeneca (all institution, Takeda and Beigene under negotiation); advisory board: BMS, Eli Lilly, Roche Genentech, Pfizer, Takeda, MSD, Merck, Novartis, Boehringer Ingelheim, Amgen, Janssen (all institution, Roche one time self); speaker: MSD, Lilly (institution); travel/conference reimbursement: Roche Genentech (self); mentorship program with key opinion leaders: funded by AstraZeneca; fees for educational webinars: Benecke, Medtalks, VJOncology (self), high5oncology (institution); interview sessions funded by Roche Genentech, Bayer, Lilly (institution); local PI of clinical trials: AstraZeneca, Novartis, BMS, MSD /Merck, GSK, Takeda, Blueprint Medicines, Roche Genentech, Janssen Pharmaceuticals, Mirati, outside the submitted work; TH reports research funding: Roche, Boehringer Ingelheim, AstraZeneca (all institution); advisory board: BMS, Roche, Merck, Pfizer; local PI of clinical trials: AstraZeneca, GSK, Novartis, Merck Serono, Roche, BMS, outside the submitted work; BH has no conflict of interest; LH has no conflict of interest; AE has no conflict of interest; SH reports advisory board/grants: Abbvie, AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Janssen, GSK, Loxo, MSD, Novartis, Roche, Takeda, outside the submitted work; AD reports research support from Amgen; consulting fees from Roche, Boehringer Ingelheim, AstraZeneca, Pharmamar, Bayer, Sanofi, and Amgen; payment for lectures or presentations from Eli Lily, AstraZeneca, Chiesi, Pfizer, Takeda and Jansen; participation in data safety monitoring board for Roche and Takeda., outside the submitted work; CL reports participation in advisory boards: Amgen, AstraZeneca, BMS, MSD, Roche, outside the submitted work; AL reports grants: BMS, MSD, Boehringer Ingelheim, AstraZeneca (all institution); non-financial support from Merck Serono, Roche, outside the submitted work; MH reports research support from Astrazeneca, BMS, Janssen, Stichting Treatmeds, Merck, MSD, Novartis, Pamgene, Pfizer, Roche; fee or other (financial payment): Abbvie, Astrazeneca, BMS, Lilly, MSD, Novartis, Pfizer, Roche, outside the submitted work; AW has received a research grant regarding the submitted work from AstraZeneca; other research grants: Boehringer-Ingelheim, Roche, Pfizer, Takeda (all institution); consulting fees: AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Merck, Novartis, Roche, Pfizer, Takeda (all institution), outside the submitted work.

Funding Information:
This work was supported by AstraZeneca [grant number ESR-16-12212].

Publisher Copyright:
© 2022 The Authors

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