A Phase Ib/II Study of Pemigatinib in Combination with Paclitaxel in Patients with Gastric Cancer with FGFs/FGFRs Alterations.
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.
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.
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%).
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.
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.
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%).
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.
Authors
Jung Jung, Park Park, Kim Kim, Kim Kim, Yun Yun, Hwang Hwang, Kim Kim, Lee Lee, Kim Kim, Lee Lee, Koo Koo, Jeung Jeung, Zang Zang, Song Song, Rha Rha
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