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

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

doi:10.1016/j.lungcan.2022.06.012

Cited by 34 publications

(27 citation statements)

References 39 publications

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“… 80 – 83 Based on this rationale, osimertinib at 160 mg OM has been evaluated in two phase II trials ECOG-ACRIN 5162 and POSITION20. 46 – 48 The reported ORR and PFS was 25% and 27%: 9.7 and 5.5 months, respectively, as well as AEs consistent with other reports of this regimen.…”

Section: Systemic Therapiessupporting

confidence: 86%

Advances in the management of non-small-cell lung cancer harbouring EGFR exon 20 insertion mutations

et al. 2023

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Epidermal growth factor receptor ( EGFR) mutation is one of the key oncogenic mutations in non-small-cell lung cancer with adenocarcinoma histology. Exon 19 deletions and exon 21 L858R substitutions account for 90%, while EGFR exon 20 insertions constitute 4–10% of EGFR mutations and are the third most prevalent activating EGFR mutations. EGFR exon 20 insertions are associated with decreased sensitivity to EGFR tyrosine kinase inhibitors and, until recently, effective targeted therapy against these tumours remained an unmet clinical need and chemotherapy was the only treatment of choice available. The approval of amivantamab and mobocertinib for patients who have progressed after chemotherapy represents an important step forward in the management of these patients. Here in this review, we summarize the epidemiology, structure and the tumour microenvironment of EGFR exon 20 insertion and also review the systemic treatments, including targeted therapies and ongoing clinical trials in EGFR exon 20 insertion mutations, as well as detection methods for EGFR exon 20 insertion. Lastly, resistant mechanisms and future directions are addressed.

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Section: Systemic Therapiessupporting

confidence: 86%

Advances in the management of non-small-cell lung cancer harbouring EGFR exon 20 insertion mutations

et al. 2023

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“… 26 Another phase 2 trial at the 160 mg dose of osimertinib had an ORR of 28% and a mPFS of 6.8 months. 27 Although there may be some activity in EGFR exon 20 insertion NSCLC, particularly at the 160 mg dose, it is not comparable with the efficacy of osimertinib in patients with the canonical Ex19del and L858R activating mutations in EGFR . The bispecific EGFR-MET monoclonal antibody amivantamab and the EGFR TKI mobocertinib are currently approved as second-line therapy.…”

Section: Discussionmentioning

confidence: 99%

“… 25 A more recent phase 2 trial at the 160 mg dose of osimertinib revealed an ORR of 25% and a mPFS of 9.7 months. 26 , 27 …”

Section: Introductionmentioning

confidence: 99%

Osimertinib in NSCLC With Atypical EGFR-Activating Mutations: A Retrospective Multicenter Study

Ji¹,

Aredo²,

Piper-Vallillo³

et al. 2023

JTO Clinical and Research Reports

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“…POSITION20 trial was a multicenter phase II study in Netherlands involving 25 pretreated or treatment-na€ ıve patients and the results showed the ORR was 28% (95% confidence interval [CI], 12-49%), with a median DOR of 5.3 months. The median PFS was 6.8 months and the median OS was 15.2 months [41]. High dose osimertinib showed modest antitumor activity in the prospective studies.…”

Section: Third-generation Epidermal Growth Factor Receptor-tyrosine K...mentioning

confidence: 91%

Targeting exon 20 insertion mutations in lung cancer

Yang

Wang

2022

Current Opinion in Oncology

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Purpose of reviewThe application of tyrosine kinase inhibitor (TKI) has successfully changed the standard of care in epidermal growth factor receptor (EGFR) positive non-small cell lung cancer. However, clinical survivals for patients with EGFR exon 20 insertions have failed to improve over the long period and the mutation appeared resistant to EGFR-TKIs. This overview focused on the current treatment strategies, summarized the emerging regimens for patients with EGFR exon 20 insertions, and demonstrated historical challenges and future development.Recent findingCurrent clinical trials suggested that several regimens selectively-targeted EGFR exon 20 insertions presented potent antitumor activity, like mobocertinib and the bispecific anti-EGFR-MET monoclonal antibody amivantamab and were approved by Food and Drug Administration (FDA) in patients progressed beyond first-line treatment. Novel treatments, including DZD9008, CLN-081, revealed modest clinical efficacy as well and clinical trials are underway, which may lead to improvement of survival outcomes.SummaryRecent clinical evidence indicates that targeted therapies could improve survival benefits to some extent. More efforts on drug development are underway to bring higher response rates both extracranial and intracranial, sustained clinical remission, and better survival benefits.

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

Cited by 34 publications

References 39 publications

Advances in the management of non-small-cell lung cancer harbouring EGFR exon 20 insertion mutations

Advances in the management of non-small-cell lung cancer harbouring EGFR exon 20 insertion mutations

Osimertinib in NSCLC With Atypical EGFR-Activating Mutations: A Retrospective Multicenter Study

Targeting exon 20 insertion mutations in lung cancer

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