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Pan-FGFR Tyrosine Kinase Inhibitor Treatment Is Less Effective in Patients with FGFR Amplifications

Clinical benefit of FGFR inhibition is stronger in patients with an FGFR fusion or mutation compared to FGFR amplification
02 Mar 2021
Personalised medicine

New insights into the clinical benefit of fibroblast growth factor receptor (FGFR) inhibitor treatment according to the FGFR alterations occurring in several different cancer types that may help guide clinical decisions were presented at the ESMO Targeted Anticancer Therapies (TAT) Virtual Congress 2021 held on March 1-2, 2021.

Cédric Pobel of the DITEP, Institut Gustave Roussy in Villejuif, France explained that FGFR alterations including amplification, fusion and mutation are found in several cancer types, but the exact alterations that affect clinical efficacy of FGFR inhibitors have yet to be clarified.

Patients with several tumour types were included in the analysis

To this end, Dr. Pobel and co-investigators retrospectively assessed data from patients treated with pan-FGFR inhibitors in phase I/II trials at the Gustave Roussy from February 2011 to June 2020. Data from the JnJ-42756493 (NCT01703481; published May 2019), 14 BGJ-398 (NCT01004224; published November 2016), TAS-120 (NCT02052778; published July 2020), and INCB-54828-202 (NCT02924376; published July 2020) studies were included.

The cohort included 92 patients; of these, the most frequent tumour types were urothelial cancer, which occurred in 23.9% of patients, cholangiocarcinoma in 21.7%, breast cancer in 20.7%, and central nervous system cancer in 13%.

Among these patients, 22 had FGFR amplification, 33 had FGFR fusion, and 37 had FGFR mutation. Patients with an amplification tended to be younger with a median age of 43 years (p = 0.02) and patients with a mutation were older with a median age of 60.5 years (p = 0.03), as compared to patients with other FGFR alterations.

Patients with FGFR amplifications demonstrated shorter survival and lower response rates

Patients with an amplification demonstrated shorter progression-free survival (PFS) compared to patients with other alterations; median PFS was 2.23 months in the amplification cohort compared to 5.23 months in patients with other alterations (hazard ratio [HR] 2.64, 95% confidence interval [CI] 1.55-4.51; p < 0.01).

Patients with an FGFR fusion experienced prolonged PFS compared to those with other alterations of median 6.20 months versus 2.70 months, respectively (HR 0.61; 95% CI 0.38-0.98; p = 0.04).

Similar PFS was observed in patients with FGFR mutation compared to other alterations of median 2.77 months versus 3.67 months, respectively (HR 0.91; 95% CI 0.57-1.44; p = 0.70).

Pan-FGFR-Tyrosine-Kinase-Inhibitor-Treatment-Is-Less-Effective-in-Patients-with-FGFR-Amplifications

Progression-free survival is shorter for patients with a FGFR amplification treated by pan-FGFR inhibitors compared to fusion and mutation.

© Cédric Pobel.

No significant difference in overall survival was found.

The best response in the FGFR amplification, fusion, and mutation cohorts was partial response, which was observed in one (4.5%), 13 (39.4%), and 10 (27%) patients, respectively (p = 0.03). In the respective cohorts, stable disease was achieved by 14 (63.6%), 12 (36.4%), and 17 (45.9%; p = 0.10) patients, whereas 7 (31.8%), 8 (24.2%), and 10 (27.0%) patients experienced disease progression (p = 0.80).

Conclusions

Based upon this analysis of data from several clinical studies, the authors concluded that the clinical benefit of FGFR inhibition is stronger in patients with an FGFR fusion or mutation compared to FGFR amplification.

According to the investigators, the role of pan-FGFR inhibitors in amplified tumours remains unclear and requires further investigation.

This study did not receive external funding.

Reference

34MO – Pobel C, Facchinetti F, Bahleda R, et al. Outcomes according to FGFR alteration types in patients with a solid tumour treated by a pan-FGRF tyrosine kinase inhibitor in phase I/II trials. ESMO Targeted Anticancer Therapies (TAT) Virtual Congress (1-2 March 2021).

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