Abstract 1236P
Background
Patients (pts) with advanced Non-Small Cell Lung Cancer (aNSCLC) harbouring an EGFR and HER2 exon 20 insertion mutation (ex20-ins) display a poor prognosis compare to wild type aNSCLC and their treatments remain unsatisfied. Poziotinib (POZ) a new generation tyrosine kinase inhibitor (ngTKI) demonstrated activity in EGFR and HER2 ex20-ins. The aim of this study is to compare overall survival (OS) of the expanded access program (EAP) pts cohort treated with POZ (POZ-c) with historical cohort of aNSCLC pts not treated with POZ (NPOZ-c) to assess the adding value of POZ.
Methods
We collected data from 30 pts in the POZ-c form May 2018 to April 2021 treated with POZ 16mg once daily or less and from 28 pts in the NPOZ-c from April 2010 until May 2020. None of NPOZ-c were treated with ngTKI. A propensity score approach (PCA) was used in order assess differences variable distribution (sex, age, ECOG, type of mutation, first-line (1L) therapy, baseline bone, brain, pleural-pericardial metastases (mts) among cohorts and to estimate the effect of POZ on survival. Hazard ratio (HR) was calculated under proportional hazards model.
Results
Among 58 pts included in the study at IV-stage diagnosis time median age were 58 years (y) (24 – 80 y). Most pts were female (70%), young < 70 y (76%) and had ECOG 0-1 (88%), an EGFR ex20-ins (77%), presented with bone mts (65%) and used platinum based as 1L (76%). Brain mts were present in 36%. Overall median OS (mOS) for both cohorts was 19.5 months (m) (95%CI, 16.6 – 22.3 m). No differences were seen among mOS in POZ-c and NPOZ-c: 19.2 m (95%CI 16.2 – 23.8) vs 18.2 m (95%CI 8.3 – 27.0), respectively, with a hazard ratio (HR) of 0.82 (95%CI, 0.47 – 1.44). The PCA showed that POZ-c had a worse clinical characteristics presentation at baseline (AUC=0.80) than NPOZ-c. Thus, adjusting the Cox hazard model for the PCA the risk mortality of POZ-c was reduced from 18 to 34% (HR 0.66 95%CI, 0.35 – 1.24, p value=0.207).
Conclusions
POZ showed a clinical activity in aNSCLC EGFR/HER2 ex20-ins aNSCLC pts. Despite the not significant differences between mOS among cohorts, in the adjusted model we can observe a reduction in risk mortality in the POZ-c compare to NPOZ-c, this to demonstrate the POZ adding value in improving prognosis. Due to the small sample size these data have to be validated in larger cohorts.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Prelaj: Financial Interests, Personal, Other, personal fees: Roche; Financial Interests, Personal, Other, personal fees: AstraZeneca; Financial Interests, Personal, Other, personal fees: BMS. G. Lo Russo: Financial Interests, Personal, Other, personal fees: BMS; Financial Interests, Personal, Other, personal fees: MSD; Financial Interests, Personal, Other, personal fees: AstraZeneca. R. Ferrara: Financial Interests, Personal, Other, Personal fees: MSD. F. de Braud: Financial Interests, Personal, Advisory Board: Ignyta; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Octimet Oncology; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Teofarma; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: NMS Nerviano Medical Science; Financial Interests, Personal, Advisory Board: Pharm Research Associated (U.K) Ltd.; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Ignyta; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: ACCMED; Financial Interests, Personal, Invited Speaker: Dephaforum S.r.l; Financial Interests, Personal, Invited Speaker: Nadirex; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Biotechspert Ltd.; Financial Interests, Personal, Invited Speaker: priME Oncology; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Invited Speaker: Celgene; Financial Interests, Personal, Invited Speaker: Tesaro; Financial Interests, Personal, Invited Speaker: Loxo Oncology Inc.; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Healthcare Research & Pharmacoepidemiology; Financial Interests, Personal and Institutional, Principal Investigator: Novartis; Financial Interests, Personal and Institutional, Principal Investigator: Roche; Financial Interests, Personal and Institutional, Principal Investigator: BMS; Financial Interests, Personal and Institutional, Principal Investigator: Celgene; Financial Interests, Personal and Institutional, Principal Investigator: Incyte; Financial Interests, Personal and Institutional, Principal Investigator: NMS; Financial Interests, Personal and Institutional, Principal Investigator: Merck KGAA; Financial Interests, Personal and Institutional, Principal Investigator: Kymab; Financial Interests, Personal and Institutional, Principal Investigator: Pfizer; Financial Interests, Personal and Institutional, Principal Investigator: Tesaro; Financial Interests, Personal and Institutional, Principal Investigator: MSD. M.C.C. Garassino: Financial Interests, Personal, Other, Personal fee: AstraZeneca; Financial Interests, Personal, Other, Personal fee: MSD International GmbH; Financial Interests, Personal, Other, Personal fee: BMS; Financial Interests, Personal, Other, Personal fee: Boehringer Ingelheim Italia S.p.A; Financial Interests, Personal, Other, Personal fee: Celgene; Financial Interests, Personal, Other, Personal fee: Eli Lilly; Financial Interests, Personal, Other, Personal fee: Ignyta; Financial Interests, Personal, Other, Personal fee: Incyte; Financial Interests, Personal, Other, Personal fee: Inivata; Financial Interests, Personal, Other, Personal fee: MedImmune; Financial Interests, Personal, Other, Personal fee: Novartis; Financial Interests, Personal, Other, Personal fee: Pfizer; Financial Interests, Personal, Other, Personal fee: Roche; Financial Interests, Personal, Other, Personal fee: Takeda. C. Proto: Financial Interests, Personal, Other, Personal fee: BMS; Financial Interests, Personal, Other, Personal fee: MSD. All other authors have declared no conflicts of interest.