scholarly journals Durable Response of Low-Dose Afatinib plus Cetuximab in an Adenocarcinoma Patient with a Novel EGFR Exon 20 Insertion Mutation

2019 ◽  
Vol 14 (10) ◽  
pp. e220-e221 ◽  
Author(s):  
Wenfeng Fang ◽  
Yihua Huang ◽  
Jiadi Gan ◽  
Yang W. Shao ◽  
Li Zhang
Keyword(s):  
Low Dose ◽  
Insertion Mutation ◽  
Durable Response ◽  
Exon 20

scholarly journals Durable Response to Immunotherapy Plus Chemotherapy in a Patient With Untreated, Brain-metastatic, EGFR Exon 20 Insertion Mutation Lung Adenocarcinoma

2021 ◽  
Author(s):  
jingying nong ◽  
Yanfei Gu ◽  
Shuyang Yao ◽  
Yi Zhang
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Checkpoint Inhibitors ◽  
Unmet Need ◽  
Growth Factor Receptor ◽  
Insertion Mutation ◽  
Durable Response ◽  
Lung Cancers ◽  
Advanced Stage Lung Cancer ◽  
Exon 20

Abstract Epidermal growth factor receptor (EGFR) 20 exon insertion is the second most common EGFR aberrations in non-small cell lung cancer (NSCLC). Despite some novel EGFR inhibitors showing encouraging antitumor activity, clinically obtainable management for this subset of patients remains an unmet need. Although immune checkpoint inhibitors (ICIs) have led to unprecedented clinical benefit in metastatic NSCLC, clinical evidence suggests that EGFR mutant lung cancers rarely derive benefit from treatment with ICIs. We report that a lung adenocarcinoma patient harboring an actionable gene mutation of EGFR exon 20 insertion, high PD-L1 expression, high tumor mutational burden, as well as alterations in immune-related genes including CTNNB1 (Catenin β1) S37F and ARID2 (AT-rich interactive domain-containing protein 2) E1056X responded to upfront PD-1 inhibitor plus chemotherapy. As an advanced-stage lung cancer with brain metastases indicating poor prognosis, the patient achieved an unusual and durable response over 15 months. Upfront ICIs plus chemotherapy might be an option for some NSCLC patients harboring EGFR exon 20 insertion mutation. Further study is needed to validate the predictor involved in responders to ICIs-based therapy with EGFR mutations.

scholarly journals Clinical outcomes of patients with HER2-mutant advanced lung cancer: chemotherapies versusHER2-directed therapies

2020 ◽  
Vol 12 ◽  
pp. 175883592093609
Author(s):  
Jiebai Zhou ◽  
Ning Ding ◽  
Xiaobo Xu ◽  
Yong Zhang ◽  
Maosong Ye ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Clinical Outcomes ◽  
Disease Diagnosis ◽  
Advanced Lung Cancer ◽  
Insertion Mutation ◽  
Targeted Agents ◽  
First Line ◽  
Line Therapy ◽  
Exon 20

Background: Lung cancer is now the leading cause of cancer mortality worldwide for both men and women. In non-small cell lung cancer (NSCLC), matching a specifically targeted drug to the identified driver mutation in each patient resulted in dramatically improved therapeutic efficacy, often in conjunction with decreased toxicity. Mutations in HER2 have been identified as an oncogenic driver gene for NSCLC. This retrospective study was conducted to better understand the clinical outcomes of advanced lung cancer patients harboring HER2 mutations treated with chemotherapies and HER2-targeted agents, as well as the optimal clinical choice. Methods: Patients who were diagnosed with advanced lung cancer (stage IIIB/IV) and had undergone molecular testing at Zhongshan Hospital, Fudan University, Shanghai, China from April 2016 to December 2018 were reviewed. For patients that had HER2 mutant advanced lung cancer, we analyzed their clinical and molecular features and clinical outcomes, including overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and objective response rate (ORR). Results: We identified 44 patients harboring HER2 mutations. Their median age was 56 years, with the majority being women ( n = 24), never smokers ( n = 32), and having the adenocarcinoma genotype ( n = 42). Amongst the HER2 mutations present, a 12 base pair in-frame insertion in exon 20 with p.771insAYVM was the most common subtype in patients with known detail variants of HER2 mutation (9/27). The median OS from the date of advanced disease diagnosis was 9.9 months with 24 deaths, and a median follow-up of 12.7 months for survivors. For patients with a known HER2 exon 20 insertion mutation, OS tended to be superior (though not statistically) in the first-line HER2-TKI group to that in the group receiving chemotherapy (10.8 versus 9.8 months, p = 0.40). However, patients that received first-line chemotherapy had a median PFS of 5.9 months, numerically longer than that of the HER2-TKI group (4.6 months, p = 0.63). Patients who received HER2-targeted therapy as first-line therapy had an improved OS (10.8 versus 10.1 months, p = 0.30) and PFS (4.6 versus 2.8 months, p = 0.36) relative to those who received HER2-targeted therapy as subsequent-line therapy, although they did not meet the threshold for statistical significance. Furthermore, patients with AYVM mutation were associated with poor clinical outcomes. Conclusion: Pemetrexed-based chemotherapy remains an important component of care for patients with HER2-mutant NSCLC. HER2-TKI given as an initial therapy may bring more clinical benefits than when given as a subsequent-line therapy. Refining the patient population based on patterns of HER2 variants may help improve the efficacy of anti- HER2 treatment in lung cancer. Developing highly effective and tolerable HER2-targeted agents is urgently needed for this population.

scholarly journals Successful Treatment of a Miliary Metastatic NSCLC Patient With Activating EGFR Exon 20 Insertion Mutation with Response to Poziotinib

2019 ◽  
Vol 14 (9) ◽  
pp. e198-e200 ◽  
Author(s):  
Juyin Yang ◽  
Jian Yang ◽  
Shao Ban ◽  
Xinmin Li ◽  
Xingde Chen ◽  
...  
Keyword(s):  
Successful Treatment ◽  
Nsclc Patient ◽  
Insertion Mutation ◽  
Metastatic Nsclc ◽  
Exon 20

EGFR exon 20 insertion mutation in Japanese lung cancer

Lung Cancer ◽  
2007 ◽  
Vol 58 (3) ◽  
pp. 324-328 ◽  
Author(s):  
Hidefumi Sasaki ◽  
Katsuhiko Endo ◽  
Minoru Takada ◽  
Masaaki Kawahara ◽  
Naoto Kitahara ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Insertion Mutation ◽  
Exon 20

Masterkey-01: Phase I/II, open-label multicenter study to assess safety, tolerability, pharmacokinetics, and antitumor activity of BDTX-189, an inhibitor of allosteric ErbB mutations, in patients with advanced solid malignancies.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS3665-TPS3665
Author(s):  
Erika Paige Hamilton ◽  
Manish R. Patel ◽  
Jordi Rodon ◽  
David S. Hong ◽  
Alison M. Schram ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Standard Therapy ◽  
Drug Exposure ◽  
Locally Advanced ◽  
Safety Data ◽  
Unmet Need ◽  
Primary Objective ◽  
Insertion Mutation ◽  
Phase 2 ◽  
Exon 20

TPS3665 Background: A significant unmet need exists for drugs targeting allosteric ErbB mutations (non-canonical mutations outside the ATP binding site). Current EGFR and HER2 tyrosine kinase inhibitors or mAbs have limited antitumor activity against allosteric mutations, resulting in toxicity before adequate drug exposure (Connell and Doherty, 2017). BDTX-189 is a potent and selective orally available irreversible inhibitor targeting unique oncogenic driver mutations of ErbB kinases in EGFR and HER2, while sparing WT EGFR. Preclinical studies demonstrated antitumor activity across a range of allosteric ErbB mutants, including extracellular domain allosteric mutations of HER2 as well as EGFR and HER2 kinase domain exon 20 insertions (Buck, 2019). This first-in-human trial (NCT04209465) is aimed to determine the recommended phase 2 dose (RP2) and schedule (Phase 1, P1), and evaluate the efficacy (Phase 2, P2) of BDTX-189. P1 primary objective is to determine the RP2 dose and schedule of monotherapy BDTX-189. Secondary objectives include assessment of safety, tolerability, pharmacokinetics (PK), pharmacodynamic (PD) effects in tumor, and preliminary efficacy. The P2 primary objective is to assess antitumor activity of monotherapy BDTX-189. Methods: The study will enroll patients (pts) ≥18 yrs with histologically or cytologically confirmed locally advanced or metastatic solid tumors with no standard therapy available or for whom standard therapy is unsuitable or intolerable. P1 dose-escalation will use a BOIN design (Yuan, 2016) and will enroll ≤ 88 pts with allosteric HER2 or HER3 mutation; EGFR or HER2 exon 20 insertion mutation; HER2 amplified or overexpressing tumor; or EGFR exon 19 deletion or L858R mutation. BDTX-189 will be dosed orally (PO) initially QD in 3 wk cycles. Regimen optimization will use PK, PD and safety data and may explore a BID schedule. An expansion cohort of ≤12 pts will further evaluate safety and preliminary efficacy of BDTX-189 prior to P2. P2, utilizing a Simon 2-stage design, will enroll ≤100 pts with NSCLC with EGFR or HER2 exon 20 insertion mutations (cohort 1); breast cancer with an allosteric ErbB mutation (cohort 2); tumors (except breast) with S310F/Y mutation (cohort 3); and other allosteric ErbB mutations not defined in cohorts 1-3 (cohort 4). Assessments include safety, tolerability, DLTs, evaluation of MTD, PK, PD, and preliminary antitumor activity. Enrollment began 1/2020. Clinical trial information: NCT04209465 .

scholarly journals 1236P Poziotinib in NSCLC harbouring EGFR or HER2 exon 20 insertion mutation

2021 ◽  
Vol 32 ◽  
pp. S976-S977
Author(s):  
A. Prelaj ◽  
A. Bottiglieri ◽  
E. Galli ◽  
G. Lo Russo ◽  
R. Ferrara ◽  
...  
Keyword(s):  
Insertion Mutation ◽  
Exon 20

scholarly journals 1405P Survival of patients with non-small cell lung cancer and exon 20 insertion mutation from the Czech Republic

2020 ◽  
Vol 31 ◽  
pp. S890
Author(s):  
J. Skrickova ◽  
M. Pesek ◽  
P. Opalka ◽  
L. Koubkova ◽  
M. Zemanová ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Czech Republic ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Insertion Mutation ◽  
Small Cell Lung ◽  
The Czech Republic ◽  
Exon 20
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