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

doi:10.1016/j.lungcan.2022.06.012

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 journal › Article › Academic › peer-review

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 language	English
Pages (from-to)	133-140
Number of pages	8
Journal	Lung Cancer
Volume	170
Early online date	23 Jun 2022
DOIs	https://doi.org/10.1016/j.lungcan.2022.06.012
Publication status	Published - Aug 2022

Keywords

CELL LUNG-CANCER
Epidermal growth factor receptor
Exon 20 mutation
INSERTION MUTATION
Non -small cell lung cancer
Osimertinib
Tyrosine kinase inhibitors

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Zwierenga, F., van Veggel, B., Hendriks, L. E. L., Hiltermann, T. J. N., Hiddinga, B. I., Hijmering Kappelle, L. B. M., Ter Elst, A., Hashemi, S. M. S., Dingemans, A.-M. C., van der Leest, C., de Langen, A. J., van den Heuvel, M. M., & van der Wekken, A. J. (2022). High dose osimertinib in patients with advanced stage EGFR exon 20 mutation-positive NSCLC: Results from the phase 2 multicenter POSITION20 trial. Lung Cancer, 170, 133-140. https://doi.org/10.1016/j.lungcan.2022.06.012

@article{345fcb37b8a14b939ba8ef6560b9f8b9,

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

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 na{\"i}ve 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.",

keywords = "CELL LUNG-CANCER, Epidermal growth factor receptor, Exon 20 mutation, INSERTION MUTATION, Non -small cell lung cancer, Osimertinib, Tyrosine kinase inhibitors",

author = "Fenneke Zwierenga and {van Veggel}, Bianca and Hendriks, {Lizza E L} and Hiltermann, {T Jeroen N} and Hiddinga, {Birgitta I} and {Hijmering Kappelle}, {Lucie B M} and {Ter Elst}, Arja and Hashemi, {Sayed M S} and Dingemans, {Anne-Marie C} and {van der Leest}, Cor and {de Langen}, {Adrianus J} and {van den Heuvel}, {Michel M} and {van der Wekken}, {Anthonie J}",

year = "2022",

month = aug,

doi = "10.1016/j.lungcan.2022.06.012",

language = "English",

volume = "170",

pages = "133--140",

journal = "Lung Cancer",

issn = "0169-5002",

publisher = "Elsevier Ireland Ltd",

}

Zwierenga, F, van Veggel, B, Hendriks, LEL, Hiltermann, TJN, Hiddinga, BI, Hijmering Kappelle, LBM, Ter Elst, A, Hashemi, SMS, Dingemans, A-MC, van der Leest, C, de Langen, AJ, van den Heuvel, MM & van der Wekken, AJ 2022, 'High dose osimertinib in patients with advanced stage EGFR exon 20 mutation-positive NSCLC: Results from the phase 2 multicenter POSITION20 trial', Lung Cancer, vol. 170, pp. 133-140. https://doi.org/10.1016/j.lungcan.2022.06.012

TY - JOUR

T1 - High dose osimertinib in patients with advanced stage EGFR exon 20 mutation-positive NSCLC

T2 - Results from the phase 2 multicenter POSITION20 trial

AU - Zwierenga, Fenneke

AU - van Veggel, Bianca

AU - Hendriks, Lizza E L

AU - Hiltermann, T Jeroen N

AU - Hiddinga, Birgitta I

AU - Hijmering Kappelle, Lucie B M

AU - Ter Elst, Arja

AU - Hashemi, Sayed M S

AU - Dingemans, Anne-Marie C

AU - van der Leest, Cor

AU - de Langen, Adrianus J

AU - van den Heuvel, Michel M

AU - van der Wekken, Anthonie J

PY - 2022/8

Y1 - 2022/8

N2 - 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.

AB - 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.

KW - CELL LUNG-CANCER

KW - Epidermal growth factor receptor

KW - Exon 20 mutation

KW - INSERTION MUTATION

KW - Non -small cell lung cancer

KW - Osimertinib

KW - Tyrosine kinase inhibitors

U2 - 10.1016/j.lungcan.2022.06.012

DO - 10.1016/j.lungcan.2022.06.012

M3 - Article

C2 - 35777160

SN - 0169-5002

VL - 170

SP - 133

EP - 140

JO - Lung Cancer

JF - Lung Cancer

ER -

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

Abstract

Keywords

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