Reference Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, Variants, or PubMed publications.

Have questions, comments, or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Ref Type Journal Article
PMID (36099710)
Authors Addeo A, Rothschild SI, Holer L, Schneider M, Waibel C, Haefliger S, Mark M, Fernandez E, Mach N, Mauti L, Jermann PM, Alborelli I, Calgua B, Savic-Prince S, Joerger M, Früh M
Title Fibroblast growth factor receptor (FGFR) inhibitor rogaratinib in patients with advanced pretreated squamous-cell non-small cell lung cancer over-expressing FGFR mRNA: The SAKK 19/18 phase II study.
Journal Vol Issue Date Pages Journal Short Title
Lung cancer (Amsterdam, Netherlands) 172 2022 10 154-159 Lung Cancer
URL
Abstract Text Patients with advanced squamous-cell lung cancer (SQCLC) frequently (46%) exhibit tumor overexpression of fibroblast growth factor receptor (FGFR) messenger ribonucleic acid (mRNA). Rogaratinib is a novel oral pan-FGFR inhibitor with a good safety profile and anti-tumor activity in early clinical trials as a single agent in FGFR pathway-addicted tumors. SAKK 19/18 determined clinical activity of rogaratinib in patients with advanced SQCLC overexpressing FGFR1-3 mRNA.Patients with advanced SQCLC failing standard systemic treatment and with FGFR1-3 mRNA tumor overexpression as defined in the protocol received rogaratinib 600 mg BID until disease progression or intolerable toxicity. A 6-months progression-free survival rate (6mPFS) ≤15 % was considered uninteresting (H0), whereas a 6mPFS ≥38 % was considered promising (H1). According to a Simon 2-stage design, 2 out of 10 patients of the first stage were required to be progression-free at 6 months. Comprehensive Genomic Profiling was performedusing the Oncomine Comprehensive Assay Plus (Thermo Fisher Scientific).Between July 2019 and November 2020, 49 patients were screened and 20 were classified FGFR-positive. Among a total of 15 patients, 6mPFS was reached in 1 patient (6.7 %), resulting in trial closure for futility after the first stage. There were 7 (46.7 %) patients with stable disease and 5 (33.3 %) patients with progressive disease. Median PFS was 1.6 (95 % CI 0.9-3.5) months and median overall survival (OS) 3.5 (95 % CI 1.0-5.9) months. Most frequent treatment-related adverse events (TRAEs) included hyperphosphatemia in 8 (53 %), diarrhea in 5 (33 %), stomatitis in 3 (20 %) and nail changes in 3 (20 %) patients. Grade ≥3 TRAEs occurred in 6 (40 %) patients. No associations between mutational profile and treatment outcome were observed.Despite preliminary signals of activity, rogaratinib failed to improve PFS in patients with advanced SQCLC overexpressing FGFR mRNA. FGFR inhibitors in SQCLC remain a challenging field, and more in-depth understanding of pathway crosstalks may lead to the development of drug combinations with FGFR inhibitors resulting in improved outcomes.

Filtering

  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

  • Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR1 over exp lung squamous cell carcinoma no benefit Rogaratinib Phase II Actionable In a Phase II trial (SAKK 19/18), Rogaratinib (BAY 1163877) treatment did not meet its primary endpoint for 6-month progression-free survival (PFS) in patients with advanced lung squamous cell carcinoma harboring overexpression of FGFR1, FGFR2, or FGFR3, and resulted in only 6.7% (1/15) of patients achieving 6-month PFS, with no objective responses, a median PFS of 1.6 months, and a median overall survival of 3.5 months (PMID: 36099710; NCT03762122). 36099710
FGFR2 over exp lung squamous cell carcinoma no benefit Rogaratinib Phase II Actionable In a Phase II trial (SAKK 19/18), Rogaratinib (BAY 1163877) treatment did not meet its primary endpoint for 6-month progression-free survival (PFS) in patients with advanced lung squamous cell carcinoma with overexpression of FGFR1, FGFR2, or FGFR3, and resulted in only 6.7% (1/15) of patients achieving 6-month PFS, with no objective responses, a median PFS of 1.6 months, and a median overall survival of 3.5 months (PMID: 36099710; NCT03762122). 36099710
FGFR3 over exp lung squamous cell carcinoma no benefit Rogaratinib Phase II Actionable In a Phase II trial (SAKK 19/18), Rogaratinib (BAY 1163877) treatment did not meet its primary endpoint for 6-month progression-free survival (PFS) in patients with advanced lung squamous cell carcinoma with overexpression of FGFR1, FGFR2, or FGFR3, and resulted in only 6.7% (1/15) of patients achieving 6-month PFS, with no objective responses, a median PFS of 1.6 months, and a median overall survival of 3.5 months (PMID: 36099710; NCT03762122). 36099710