Infigratinib Opens Up Options for Patients With FGFR2-Mutant Cholangiocarcinoma

OncologyLive, Vol. 22/No. 15, Volume 22, Issue 15

Partner | Cancer Centers | <b>MD Anderson</b>

Milind Javle, MD, discusses the potential impact of infigratinib on the treatment landscape of FGFR2 fusion–positive cholangiocarcinoma.

The identification of actionable genomic alterations in patients with cholangiocarcinoma has begun to change the standard of care for this patient population. Of particular interest to investigators are FGFR alterations, which have been shown to drive tumorigenesis and are present in approximately 14% of cholangiocarcinoma cases.1

Infigratinib (Truseltiq), a selective tyrosine kinase inhibitor, has demonstrated activity against tumors with FGFR alterations, eliciting clinically meaningful response rates and tolerable safety profile. The current standard of care for these patients in the second-line setting is chemotherapy, which according to results of a retrospective analysis of 37 patients elicited an overall response rate (ORR) of 5.4% and a median progression-free survival (PFS) of 4.6 months.1

In May, results of the phase 2 CBGJ398X2204 trial (NCT02150967) led to the accelerated approval of infigratinib for patients with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or other rearrangement as detected by an FDA-approved test.2

Specifically, the analysis showed that in the 108-patient efficacy population, infigratinib elicited an ORR of 23% (95% CI, 16%-32%), with 1 patient experiencing a complete response. The median duration of response (DOR) was 5 months (95% CI, 3.7-9.3), and 8 patients (32%) had a DOR of at least 6 months.3

In an interview with OncLive®, Milind Javle, MD, a professor in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston, discussed the potential impact of infigratinib on the treatment landscape of FGFR2 fusion– positive cholangiocarcinoma.

OncLive: How does this approval shift the cholangiocarcinoma treatment paradigm? 

Javle: Cholangiocarcinoma is generally treated with first-line chemotherapy, such as gemcitabine and cisplatin, and second-line chemotherapy with FOLFOX. The results [using] both of those approaches are suboptimal. For instance, with FOLFOX, the PFS is [approximately] 4 months, and the overall survival is only 6 months. So now patients with cholangiocarcinoma [harboring] FGFR2 fusions have a viable alternative that is effective in their management, which is for second and subsequent lines of treatment. We hope that in the future, we will be able to use it in earlier lines of therapy.

The patients enrolled in the [CBGJ398X2204] trial had locally advanced or metastatic cholangiocarcinoma or bile duct cancer that had progressed or were intolerant to gemcitabine-based chemotherapy. [Additionally], these were patients with FGFR gene fusions or rearrangements. These patients had been treated previously with chemotherapy. Then, if they had FGFR fusions or rearrangements, they received infigratinib monotherapy at a dose of 125 mg daily for 21 days.

This study enrolled 120 patients with FGFR2 gene rearrangements or fusions. These patients were then treated with infigratinib. Several patients were excluded who did not meet the eligibility criteria. In the final analysis, [108 patients were treated] and the ORR, as noted by independent radiological assessment, was 23%. In terms of investigator-assessed response, the response rate was 34%. I also want to mention that the DOR, which was a primary end point of the trial, was 5 months; the DCR was 4% [and the] median PFS was 7.3 months.

What do we know about infigratinib in terms of safety, and what do clinicians need to be aware of when prescribing it? 

The adverse events can be classified into class specific, [which] is specific to all FGFR inhibitors, and then others. The class-specific, FGFR-specific adverse events, which are sort of common to all FGFR inhibitors, include high phosphate level, or hyperphosphatemia, and a proportion [of patients] also [experience] hypophosphatemia. We also have PPE [palmar-plantar erythrodysesthesia] syndrome or hand-foot syndrome, mouth sores, and dry mouth. The more significant toxicities, which are mechanism based, include ectopic calcification of the tissues. They also include ocular disorders, such as dry eyes, central serous retinopathy, or retinal pigment epithelial detachment.

What does the future hold for infigratinib?

[The ongoing trial PROOF trial (NCT03773302) is comparing] infigratinib to gemcitabine and cisplatin in the first-line setting for patients who have not received prior systemic chemotherapy. The results of that trial should be very informative. We hope that patients can benefit with this targeted therapy and not require any subsequent chemotherapy.

However, there are further implications beyond the first-line setting. There are various other combination-therapy trials going on [in which] infigratinib is being combined with targeted agents and with immunotherapy. I hope that there will be several other alternatives for patients who have FGFR fusions and gene rearrangements.

This [CBGJ398X2204] trial has once again highlighted the importance of molecular sequencing in order to diagnose not just FGFR fusions, but several other targetable or actionable genetic alterations. It is critical that we profile these patients to find these possible avenues.


  1. Javle MM, Roychowdhury S, Kelley RK, et al. Final results from a phase II study of infigratinib (BGJ398), an FGFR-selective tyrosine kinase inhibitor, in patients with previously treated advanced cholangiocarcinoma harboring an FGFR2 gene fusion or rearrangement. J Clin Oncol. 2021;39(suppl 3):265. doi:10.1200/JCO.2021.39.3_suppl.265
  2. FDA grants accelerated approval to infigratinib for metastatic cholangiocarcinoma. FDA. Updated May 28, 2021. Accessed July 19, 2021. information-approved-drugs/fda-grants-accelerated-approval-infigratinib-metastatic- cholangiocarcinoma
  3. Truseltiq. Prescribing information. QED Therapeutics Inc; 2021. Accessed July 19, 2021.