Abstract 1388P
Background
Treatment of metastatic Non-Small Cell Lung Cancer (mNSCLC) patients (pts) with EGFR or HER2 exon 20 insertion mutation (i-mut) still remains an unmet clinical need. Up to now the standard of care, is platinum-based chemotherapy (PL) +/- immunotherapy (IO). Poziotinib (POZ), a new generation Tyrosine Kinase Inhibitor (TKI) is currently under investigation as a potential target therapy. This real-life compassionate use study aim is to describe the activity and toxicity (TOX) of POZ in mNSCLC pts with exon 20 i-mut.
Methods
Pts were treated within an expanded access program (EAP) at Istituto Nazionale Tumori of Milan. POZ (16 mg or less) was administrated orally QD and dose reduction for TOX was allowed. All necessary data were collected [e.g.: treatment outcome and Adverse Events (AEs)]. Efficacy endpoints were median Progression-Free Survival (mPFS), Overall Response Rate (ORR), Disease Control Rate (DCR) assessed by RECIST v1.1. TOX and Overall Survival (mOS) were also evaluated.
Results
Among 29 pts, median age was 59 years (25-80), most were female (76%), Performance Status 0-1 (83%), EGFR i-mut (72%) and pre-treated (93%) with a median of 1 prior therapy (0-6)(e.g.: PL, TKIs, IO). 72% started POZ at a dose 16 mg. At baseline bone, brain, liver, metastases, and pleural/pericardial effusion were present in 83%, 55%, 41% and 65% of pts, respectively. At data cut-off, progression occurred in 17/29 (58%) and death in 10/29 (34%). Median follow-up was 8 months (mo) (CI95% 4.1 – 11.8 mo), the mPFS was 5.6 mo (CI95% 3.6–7.1 mo) and the mOS 9.5 mo (CI95% 5.1–not-reached mo). The ORR was 27.6% (EGFR 19%, HER2 50%) and DCR 69% confirmed by a central review. 100% of pts experienced AEs, 89% a dose interruption and 76% a dose reduction. G3-4 AEs were reported in 66% of pts and were: skin rash (50%), gastrointestinal toxicities (31%, mostly diarrhea) mucositis (7%), paronychia (3%). One G5 pneumonitis possible drug-related occurred.
Conclusions
POZ demonstrated clinical activity in mNSCLC pts with EGFR and HER2 exon 20 i-mut. Reported TOX rate was high leading to a frequent dose interruption and reduction possibly reducing PFS in patients with good ORR and DCR. ZENITH20, an ongoing trial is evaluating lower dose and new dose schedule (e.g. BID).
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Fondazione IRCCS Istituto Nazionale Tumori di Milano.
Funding
Has not received any funding.
Disclosure
A. Prelaj: Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: AstraZeneca; Honoraria (self): BMS. C. Proto: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD International GmbH; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Eli Lilly. G. Lo Russo: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD. D. Signorelli: Advisory/Consultancy: AstraZeneca; Research grant/Funding (self), Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (self), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Research grant/Funding (self), Travel/Accommodation/Expenses: Roche; Research grant/Funding (self), Travel/Accommodation/Expenses: MSD International GmbH. M.C. Garassino: Advisory/Consultancy, Speaker Bureau/Expert testimony, Leadership role, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Leadership role, Travel/Accommodation/Expenses: MSD International GmbH; Advisory/Consultancy, Speaker Bureau/Expert testimony, Leadership role, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony, Leadership role, Travel/Accommodation/Expenses: Boehringer Ingelheim Italia SpA; Advisory/Consultancy, Speaker Bureau/Expert testimony, Leadership role, Travel/Accommodation/Expenses: Celgene; Advisory/Consultancy, Speaker Bureau/Expert testimony, Leadership role, Travel/Accommodation/Expenses: Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Leadership role, Travel/Accommodation/Expenses: Ignyta; Advisory/Consultancy, Speaker Bureau/Expert testimony, Leadership role, Travel/Accommodation/Expenses: Incyte; Advisory/Consultancy, Speaker Bureau/Expert testimony, Leadership role, Travel/Accommodation/Expenses: Inivata; Advisory/Consultancy, Speaker Bureau/Expert testimony, Leadership role, Travel/Accommodation/Expenses: MedImmune; Advisory/Consultancy, Speaker Bureau/Expert testimony, Leadership role, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Leadership role, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Leadership role, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Leadership role, Travel/Accommodation/Expenses: Takeda; Honoraria (institution): Foundation Medicine; Research grant/Funding (institution): AIRC; Research grant/Funding (institution): AIFA; Research grant/Funding (institution): TRANSCAN; Research grant/Funding (institution): Italian Moh; Honoraria (institution): Tiziana. All other authors have declared no conflicts of interest.