ADVERTISEMENT
Pemigatinib for Cholangiocarcinoma with FGFR2 Fusions or Rearrangements
Arndt Vogel, MD, Hannover Medical School, Hannover, Germany, shares results from the phase 2, FIGHT-202 trial which evaluated the efficacy and safety of pemigatinib, oral, potent, selective fibroblast growth factor receptor (FGFR)1, 2, and 3 inhibitor, in patients with previously treated, locally advanced or metastatic cholangiocarcinoma. In this podcast, Dr Vogel focuses on the results of cohort A, patients with confirmed FGFR2 fusions/rearrangements.
These findings were presented at the 2022 ESMO World Gastrointestinal Congress.
Transcript:
Hello, my name is Arndt Vogel. I'm a hepatologist from Hanover in Germany, and I would like to give you a brief update on the data we presented at ESMO GI in Barcelona on the FIGHT-202 study. As of now, in cholangiocarcinoma, we can find a lot of druggable iterations. Specifically in intrahepatic cholangiocarcinoma, in around 10% of patients we can detect FGFR2 fusions, and we have seen an approval of pemigatinib for these patients with FGFR2 fusion based on the FIGHT-202 study. We presented an update on the efficacy data from this pivotal study. Interestingly enough, it was a Phase 2, single-arm study without a control group.
Single-arm study is not completely correct because it was actually a three-arm study. The largest cohort were patients with FGFR2 fusion, clearly our target population. Cohort B included patients with other genetic iterations, specifically mutations in the FGFR2 pathway. And the third cohort were patients without any genetic iterations in the FGFR2 pathway, kind of a control group, but we did not aim to compare the arms with each other.
Pemigatinib is an FGFR2 inhibitor. It's an oral drug and was given two weeks on, one week off within the study. In terms of baseline characteristics, we observed that in cohort A, in patients with FGFR2 fusions, we observed slightly more female and younger patients. This is in line with data we have seen from other retrospective and prospective studies, that not only do we find these iterations primarily in intrahepatic cholangiocarcinoma, but also the slight predominance of females and younger patients. The other two cohorts were, not surprisingly, patients with intra- and extrahepatic cholangiocarcinoma, as you would expect. The primary endpoint in the study was the overall response rate.
It was 37% and these responses were durable. Median duration of response was 9.1 months, which is really impressive. And there were some patients with really long term tumor control. The high response rate and long duration of control, of course also translated in decent median progression free survival and overall survival. In this final analysis you observed a median PFS of seven months and a median overall survival of 17.5 months. If you take all these efficacy data, I think they fit very nicely into the data we have seen also from other FGFR2 inhibitors. We have a high response rate, a very high disease control rate of more than 80%. And the PFS is between six and nine months. Data we have seen for infigratinib, pemigatinib, and futibatinib and maybe it will change a little bit with the more recently developed FGF inhibitors, but here we need to wait for final data. Similarly, the overall survival is in line with what we would have seen with the other FGF inhibitor, between 15 and 30 months, which is really remarkable for these really difficult to treat tumors.
Usually in the second line setting, we see single digit response rate PFS of three months and median overall survival of six months. So here there's clearly an improvement. In terms of side effects, there were no safety signals. What we have observed before: changes in the phosphide levels, skin toxicity, neurotoxicity, GI toxicity, fatigue, this is what we observed with all these FGF inhibitors in this long term follow up study. So I think in summary, this data confirm the efficacy of pemigatinib. The response rate PFS overall survival is clinically meaningful. And I think also justified the further development of these drugs into the first line setting, as you know, three drugs, futibatinib, infigratinib, and also pemigatinib are tested in Phase 3 studies in the first line setting. These studies still have a long way to go for the recruitment, but I think the data we have seen so far clearly justified this approach. Thank you very much.
Source:
Vogel A, Sahai V, Hollebecque A, et al. Pemigatinib for previously treated locally advanced or metastatic cholangiocarcinoma: Final results from FIGHT-202. Presented at: ESMO World Congress on Gastrointestinal Cancer; June 29-July 2, 2022. Barcelona, Spain. Abstract LBA O-2.
