Abstract 3879
Background
FGFR2 gene aberrations (GA) include fusions and mutations/amplifications, with an estimated prevalence of approximately 15% and 5% in iCCA, respectively. While FGFR2 fusions are acknowledged oncogenic drivers, the oncogenic potential of FGFR2 mutations and amplifications is less well defined, due to ambiguous available preclinical and clinical data. In a non-comparative Phase 2a study (NCT01752920), the potent pan-FGFR inhibitor DZB was administered to iCCA pts expressing either FGFR2-fusion (N = 29), FGFR2 mutations/amplifications (N = 6) or no FGFR gene aberration (N = 9). Here, we present a post-hoc analysis of outcomes of iCCA pts expressing FGFR mutations/amplifications (N = 6) or no FGFR GA (N = 9) as compared to previously reported data of iCCA pts (N = 29) expressing FGFR2 fusions (Mazzaferro et al. 2018 BJC).
Methods
Pts received 300 mg DZB QD PO. Eligibility criteria included a locally confirmed (FISH or NGS) testing of FGFR2 GA (fusions vs mutations/amplifications or no aberrations). Objective responses were determined per RECIST 1.1. Disease control rate (DCR) was defined by the summation of CR, PR and SD, and PFS, calculated from treatment initiation until disease progression or death.
Results
The table shows the efficacy outcomes in the 3 patient groups. Types of drug-related adverse events were similar across groups. No new safety signals were identified.Table:
721P
iCCA patient group | FGFR2 fusion N = 29 | FGFR2 mutation/ amplification N = 6 | No FGFR2 genomic aberration N = 9 |
---|---|---|---|
Objective response rate (RECIST 1.1) | 6 (21%) | 0 (0%) | 0 (0%) |
DCR (PR or SD) | 24 (83%) | 4 (67%) | 2 (22%) |
Any target lesion diameter reduction | 18 (62%) | 4 (67%) | 0 (0%) |
Median (95% CI) Progression free survival (PFS), months | 5.7 | 6.7 | 1.5 |
(4.0-9.2) | (1.0-14.7) | (0.7 – NA) | |
% PFS at 3 months | 83% | 67% | 0% |
% PFS at 6 months | 47% | 50% | 0% |
Conclusions
Anti-tumor efficacy of DZB as measured by DCR and PFS in iCCA patients harboring an FGFR2 GA seems to be similar for patients with FGFR2 fusions and FGFR2 mutations/amplifications, while patients without any detectable FGFR GA appear to derive no benefit from DZB treatment. While the influence of prognostic variables still has to be confirmed, the anti-tumor efficacy of DZB seen in pts with FGFR2 GA other than fusions warrant further clinical investigation.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Basilea Pharmaceutica International Ltd.
Funding
Basilea Pharmaceutica International Ltd.
Disclosure
S. Braun: Full / Part-time employment: Basilea Pharmaceutica Int. Ltd.; Shareholder / Stockholder / Stock options: Ipsen. B. El-Rayes: Advisory / Consultancy: Merrimack; Advisory / Consultancy: BTG; Honoraria (self), Advisory / Consultancy: Bayer; Advisory / Consultancy: Loxo; Honoraria (self), Advisory / Consultancy: RTI Health Solutions; Honoraria (self), Speaker Bureau / Expert testimony: Lexicon; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Taiho Pharmaceutical; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): Cleave Biosciences; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): AVEO; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Hoosier Cancer Research Network; Research grant / Funding (institution): Five Prime Therapeutics; Research grant / Funding (institution): PPD; Research grant / Funding (institution): Merck; Research grant / Funding (institution): ICON Clinical Research. W.P. Harris: Advisory / Consultancy: Neo Therma; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): ArQule; Research grant / Funding (institution): Halozyme; Research grant / Funding (institution): Nordion; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Agios. N. Damjanov: Advisory / Consultancy: Bayer; Advisory / Consultancy: Amgen; Advisory / Consultancy: Celgene; Honoraria (self): Sirtex Medical. L. Rimassa: Advisory / Consultancy: Bayer; Advisory / Consultancy: Sirtex Medical; Advisory / Consultancy: Italfarmaco; Advisory / Consultancy: Sanofi; Advisory / Consultancy, Travel / Accommodation / Expenses: ArQule; Advisory / Consultancy: Baxter; Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Amgen; Advisory / Consultancy: Incyte; Advisory / Consultancy: Celgene; Advisory / Consultancy: Eisai; Advisory / Consultancy: Lilly; Honoraria (self): AstraZeneca; Honoraria (self): AbbVie; Honoraria (self): Gilead Sciences; Honoraria (self): Roche. F. Braiteh: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Clovis Oncology; Shareholder / Stockholder / Stock options: Agios; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Insys Therapeutics; Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Tesaro; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Genentech/Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Incyte; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Travel / Accommodation / Expenses: Regeneron; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Celgene; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Lexicon; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Taiho Pharmaceutical; Travel / Accommodation / Expenses: Heron. S. Lonardi: Advisory / Consultancy, Research grant / Funding (self): Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Merck Serono; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: Servier. M. Engelhardt: Full / Part-time employment: Basilea Pharmaceutica Int. Ltd. M. Saulay: Full / Part-time employment: Basilea Pharmaceutica Int. Ltd. B. Schwartz: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: ArQule; Advisory / Consultancy: CIRM. W.L. Shaib: Research grant / Funding (institution): ArQule; Research grant / Funding (institution): Lilly. V. Mazzaferro: Advisory / Consultancy: Terumo Europe NV; Speaker Bureau / Expert testimony: Ipsen AB. K.P. Papadopoulos: Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (institution): ArQule; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): ARMO BioSciences; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Calithera Biosciences; Research grant / Funding (institution): Curegenix; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Peloton Therapeutics; Research grant / Funding (institution): ADC Therapeutics; Research grant / Funding (institution): 3D Medicines; Research grant / Funding (institution): Formation Biologics; Research grant / Funding (institution): EMD Serono; Research grant / Funding (institution): Syros Pharmaceuticals; Research grant / Funding (institution): Mersana; Research grant / Funding (institution): OncoMed. All other authors have declared no conflicts of interest.
Resources from the same session
5203 - Novel fusion genes identified from matched primary and recurred breast cancers by RNA-sequencing
Presenter: Soojeong Choi
Session: Poster Display session 2
Resources:
Abstract
5873 - Association between PIK3CA mutation status and development of brain metastases in HR+/HER2- metastatic breast cancer
Presenter: Donna Fitzgerald
Session: Poster Display session 2
Resources:
Abstract
3588 - The role of AXL as mechanism of resistance to trastuzumab and a prognostic factor in breast cancer HER2 positive: a translational approach.
Presenter: Anna Adam-Artigues
Session: Poster Display session 2
Resources:
Abstract
5640 - Untargeted assessment of tumor fractions in plasma for monitoring and prognostication from metastatic breast cancer patients undergoing systemic treatment
Presenter: Marija Balic
Session: Poster Display session 2
Resources:
Abstract
2616 - Clinical application of mutational analysis in breast cancer patients: the relevance of PIK3CA analysis for precision medicine.
Presenter: Juan Miguel Cejalvo
Session: Poster Display session 2
Resources:
Abstract
3870 - A retrospective gene expression analysis of surgically-removed Breast Cancer Brain Metastasis (BCBM)
Presenter: Meritxell Mallafré-Larrosa
Session: Poster Display session 2
Resources:
Abstract
1240 - Endocrine therapy alone versus targeted combination strategy as first line treatment in elderly patients with hormone receptor-positive advanced breast cancer: meta-analysis of Phase II and III randomized clinical trials
Presenter: Claudia Omarini
Session: Poster Display session 2
Resources:
Abstract
5535 - Alpelisib (ALP) + fulvestrant (FUL) for patients with hormone receptor–positive (HR+), HER2− advanced breast cancer (ABC): management and time course of key adverse events of special interest (AESIs) in SOLAR-1
Presenter: Hope Rugo
Session: Poster Display session 2
Resources:
Abstract
3093 - Changes in Hormone-Receptor status in Luminal breast cancers between primary tumor and metastases: results of the observational cohort GIM-13 AMBRA Study
Presenter: Marina Cazzaniga
Session: Poster Display session 2
Resources:
Abstract
1378 - MONARCH 3: Updated time to chemotherapy and disease progression following abemaciclib plus aromatase inhibitor (AI) in HR+, HER2- advanced breast cancer (ABC)
Presenter: Miguel Martín
Session: Poster Display session 2
Resources:
Abstract