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Mini Oral session

34MO - 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

Date

02 Mar 2021

Session

Mini Oral session

Presenters

Cedric Pobel

Citation

Annals of Oncology (2021) 32 (suppl_1): S14-S19. 10.1016/annonc/annonc459

Authors

C.J. Pobel1, F. Facchinetti2, R. Bahleda1, L. Verlingue1, A. Gazzah1, A. Varga1, C. Baldini1, S. Champiat1, A. Marabelle1, M. Ningarhari1, A. Geraud1, Y. Loriot3, C. Massard1, J. Soria1, L. Friboulet2, A. Hollebecque1

Author affiliations

  • 1 Ditep, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 2 U981, Gustave Roussy - Cancer Campus, 94805 - Villejuif/FR
  • 3 Cancer Medicine Department, Institut Gustave Roussy, 94805 - Villejuif/FR
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Resources

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Abstract 34MO

Background

Oncogene-dependency is an important therapeutic principle. Fibroblast growth factor receptors (FGFR) alterations include amplification (amp), fusion (fus) and mutation (mut) and are found in several cancer types. Which alterations truly lead to the clinical efficacy of FGFR inhibitors need to be clarified.

Methods

We retrospectively assessed data from patients treated with pan-FGRF inhibitors in phase I/II trials at Gustave Roussy Institut including JnJ-42756493, BGJ-398, INCB-54828-202 and TAS-120 between February 2011 and June 2020.

Results

Among 92 patients 22 had a FGFR amp, 33 a FGFR fus and 37 a FGFR mut. Patients with an amp were younger (43 median age, p=0.02) and patients with a mut were older (60.5 median age, p=0.03) compared to patients with other FGFR alterations. Most frequent tumor types were urothelial cancer (23.9%), cholangiocarcinoma (21.7%), breast cancer (20.7%) and central nervous system cancer (13%). Best response rates according to alteration are listed in the table. Patients with an amp had a shorter progression free survival (PFS) compared to other alterations with a median of 2.23 months (mo) vs 5.23 mo (HR=2.64, 95% CI[1.55-4.51], p<0.01). Patients with a fus had a longer PFS than other alterations with a median of 6.20 mo vs 2.70 mo (HR=0.61, 95% CI[0.38-0.98], p=0.04). Patients with a mut had a similar PFS compared to other alterations with a median of 2.77 mo vs 3.67 mo (HR=0.91, 95% CI[0.57-1.44], p=0.70). No significant difference in overall survival was found. Table: 34MO

Best response rate according to FGFR alteration

Alteration type, n Amp (n=22) Fus (n=33) Mut (n=37) p∗
Best response, n (%)
Progression 7 (31.8) 8 (24.2) 10 (27.0)
Stable disease 14 (63.6) 12 (36.4) 17 (45.9) 0.03/0.09/1
Partial response 1 (4.5) 13 (39.4) 10 (27.0)
Best response (%) Median (range) +11 (-35; +100) -14 (-63; +174) 0 (-92; +100) <0.01/0.04/0.50

∗= amplification/fusion/mutation vs others

Conclusions

The clinical benefit of FGFR inhibition is stronger in case of FGFR fus or mut compared to FGFR amp. The role of pan-FGFR inhibitors in amplified tumors remains unclear and requires further investigation.

Clinical trial identification

JnJ-42756493 (NCT01703481) published in 2019 May; 14 BGJ-398 (NCT01004224) published in 2016 November; 21 TAS-120 (NCT02052778) published in 2020 July; 2 INCB-54828-202 (NCT02924376) published July 7.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

C.J. Pobel: Travel/Accommodation/Expenses: Amgen, Sandoz. L. Verlingue: Honoraria (self), LV reports personal fees from Adaptherapy, outside of the submitted work: Adaptherapy. J-C. Soria: Advisory/Consultancy: AbbVie, AstraZeneca, Bayer, Blend Therapeutics, Boehringer Ingelheim, Cytomix, Daiichi, Eli Lilly, Genmab, Guardant, Inivata, Merck, Netcancer, PharmaMar, Roche, Servier, Tarveda; Leadership role, Full/Part-time employment, Senior vice president AstraZeneca 09/2017-12/2019: AstraZeneca; Leadership role, Full/Part-time employment, Directeur general since 01/2020: Institut Gustave Roussy. L. Friboulet: Research grant/Funding (institution), research funding FGFR TKI: Incyte, Debiopharm. All other authors have declared no conflicts of interest.

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