High dose osimertinib in patients with advanced stage EGFR exon 20 mutation-positive NSCLC: results from the phase 2 multicenter POSITION20 trial
Mené aux Pays-bas sur 25 patients atteints d'un cancer du poumon non à petites cellules présentant des mutations de l'exon 20 du gène EGFR (âge médian : 70 ans), cet essai multicentrique de phase II évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité de l'osimertinib dispensé à haute dose (160 mg)
Introduction : Patients with life-threatening advanced non-small cell lung cancer (NSCLC) who harboran exon 20 deletion and/or insertion mutation (EGFRex20+) have limited effective treatmentoptions. 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 osimertinibin patients with EGFRex20+, T790M negative NSCLC. We allowed patients to be treatmentnaïve and to have asymptomatic brain metastases. The primary endpoint was overall response rate (ORR). Secondary outcomes were duration of response (DoR), progressionfree 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 theNetherlands. 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 mutationswere 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 15.2months (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 diseasein 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.