Table 2.

Identification of acquired resistance mutations in patients with FGFR2 rearrangements treated with pemigatinib

BaselineProgression
Patient #Tumor change from baseline, %BORPFS, monthsAnalysis platformFGFR2 rearrangementCo-alteration(s)Analysis platformFGFR2 rearrangementAcquired FGFR2 alterations (allele frequency)Co-alteration(s)
1−15.7SD13.1MSKIFGFR2–NRBF2 fusionBAP1 p.Q393*F1FGFR2–NRBF2 fusionp.N549K (23.19%)CDKN2A/B loss, BAP1 p.Q393*
2−60.5PR15.9 (censoreda)F1FGFR2–KIAA1217 fusionNoneF1FGFR2–KIAA1217 fusionp.K659M (6.07%)None
3−58.2PR6.9F1FGFR2–CCDC170 fusionPIK3CA p.E545K, BAP1 p.Q684*, AKT Amp, MDM4 Amp, PIK3C2B AmpF1FGFR2–CCDC170 fusionp.K641R (3.50%), p.N549K (4.03%)CTNNB1 p.S45C, BAP1 p.Q684*
4−33.3SD6.8F1FGFR2-AHCYL1 fusionKDR p.P1243L, TP53 p.R280G, FANCG splice siteF1FGFR2-AHCYL1 fusionp.L617V (33.9%)KDR p.P1243L, TP53 p.R280G, FANCG splice site
5−63.6PR8.8F1FGFR2–WDHD1 fusionBRD4 p.Q256fs*46, SH2B3 p.A227fs*51, FAS loss, PTEN lossWESbN/Ap.N549K (14.29%)BIRC6c splice site, ZWINTc p.F135Lfs*40
6−39.8PR6.9 (censoreda)F1FGFR2–PAWR fusionBAP1 splice site, STAG2 p.M148fs*3WESbN/Ap.E565A (6.1%), p.K641R (23.7%)BAP1 splice site, STAG2 p.M148fs*3
7−13SD8.8 (censoreda)F1FGFR2–ATAD2 fusionMCL1 Amp, NTRK1 AmpF1LFGFR2–ATAD2 fusionp.N549H (0.12%)PTEN p.T319fs*1
8−46PR9.1F1FGFR2–TRIM8 rearrangementEPHB6 p.R125QF1LFGFR2–TRIM8 rearrangementp.E565A (0.19%), p.L617V (0.32%), p.K659M (2.71%)None
  • Abbreviations: BOR, best objective response; PR, partial response; SD, stable disease; MSKI, MSK Impact; F1, FoundationOne; F1L, FoundationOne Liquid; WES, whole exome sequencing.

  • aCensored at the time of the original data cutoff of March 22, 2019 (22), but progressed afterward.

  • bMutation data only were used from whole-exome sequencing. FGFR2 fusions/rearrangements are not detectable in whole-exome sequencing data.

  • cNot present in the FoundationOne panel.