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A Phase Ib/II Study of Pemigatinib in Combination with Paclitaxel in Patients with Gastric Cancer with FGFs/FGFRs
Minkyu Jung1,2, Soo Hyun Park1, Hyoyoung Kim1
1Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
Purpose:
Pemigatinib is a selective inhibitor of fibroblast growth factor receptors (FGFR) 1-3 with demonstrated activity in tumors harboring FGFR2 fusions or amplifications. This phase Ib/II trial assessed the efficacy and safety of pemigatinib in combination with paclitaxel in patients with recurrent or advanced gastric cancer exhibiting FGFs/FGFRs alterations.
Materials And Methods:
Patients with gastric cancer harboring FGFs/FGFRs aberrations who experienced progression following first-line therapy were enrolled. The phase Ib component established the recommended phase II dose (RP2D); the phase II component evaluated clinical efficacy.
Results:
Twelve patients were enrolled. The RP2D was determined as pemigatinib 13.5 mg/day (days 1-21) plus paclitaxel 80 mg/m² (days 1, 8, 15) every 4 weeks. Median progression-free and overall survival were 4.4 and 10.5 months, respectively. Patients with FGFR2 amplification (n=6) exhibited prolonged progression-free survival (6.5 vs. 3.5 months, p=0.049), while overall survival did not differ significantly. The objective response and disease control rates were 33.3% and 91.7%, respectively. The most frequent treatment-related adverse events were neutropenia (83.3%, grade ≥3: 58.3%) and hyperphosphatemia (83.3%, grade ≥3: 33.3%).
Conclusion:
Pemigatinib plus paclitaxel demonstrated antitumor activity with an acceptable safety profile in FGFR2-amplified gastric cancer. Further investigation is warranted to elucidate resistance mechanisms and validate these findings in larger cohorts.
Insights
Pemigatinib combined with paclitaxel shows promise for advanced gastric cancer with FGFR2 alterations. This combination therapy demonstrated antitumor activity and an acceptable safety profile in a phase Ib/II trial.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Pemigatinib is a targeted therapy inhibiting fibroblast growth factor receptors (FGFR) 1-3.
- FGFR alterations, including fusions and amplifications, are implicated in various cancers.
- Gastric cancer with FGFs/FGFRs aberrations presents a therapeutic challenge.
Purpose of the Study:
- To assess the efficacy and safety of pemigatinib plus paclitaxel in recurrent or advanced gastric cancer.
- To identify patients with FGFs/FGFRs alterations who may benefit from this combination therapy.
- To establish the recommended phase II dose (RP2D) for pemigatinib and paclitaxel.
Main Methods:
- A phase Ib/II clinical trial design was employed.
- Patients with gastric cancer and FGFs/FGFRs aberrations, progressing after first-line therapy, were enrolled.
- The study determined the RP2D and evaluated clinical efficacy, including progression-free survival, overall survival, and response rates.
Main Results:
- The RP2D was pemigatinib 13.5 mg/day plus paclitaxel 80 mg/m² every 4 weeks.
- Median progression-free survival was 4.4 months and overall survival was 10.5 months.
- Patients with FGFR2 amplification showed significantly prolonged progression-free survival (6.5 vs. 3.5 months, p=0.049). Objective response rate was 33.3%.
Conclusions:
- Pemigatinib plus paclitaxel exhibits antitumor activity in FGFR2-amplified gastric cancer.
- The combination demonstrated an acceptable safety profile, with neutropenia and hyperphosphatemia as common adverse events.
- Further research is needed to explore resistance mechanisms and validate findings in larger patient cohorts.
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