A 67-year-old man was incidentally diagnosed with iCCA when he presented with gallstone pancreatitis in March 2020. There was no relevant medical or family history. He proceeded to have a left hemihepatectomy and cholecystectomy in April 2020; histology confirmed this was a complete resection of a pT2 NX R0 iCCA. This was not followed by adjuvant chemotherapy.
He was diagnosed with metastatic CCA when MRI and CT imaging in October 2020 confirmed recurrence in the liver and lung. He was enrolled into a clinical trial in December 2020 to receive cisplatin plus gemcitabine, with or without immunotherapy. At the time of enrolment, the patients had PS 0 and normal hepatic and renal functions. Four months after enrolment, in April 2021, a CT scan showed stable lung disease but progressive hepatic disease. The patient's molecular profiling showed negative HER2 and NTRK mutations, intact mismatch repair and positive FGFR2 fusion. Thus, the patient started pemigatinib 13.5 mg once daily on days 1-14 of a 21-day cycle in July 2021, alongside supportive medications: topical emollient, antiemetic and antidiarrhoeal agents.
Before the start of cycle 2 (29 July 2021), the serum phosphate level increased to 2.06 mmol/L and the patient presented with grade 1 dry mouth, mucosal dryness and diarrhoea. One month later, grade 1/2 toxicities were reported in the form of diarrhoea, abdominal pain, hair loss and nail discolouration. Therefore, the pemigatinib dose was reduced to 9 mg daily at cycle 3, significantly improving grade 2 diarrhoea and dry mouth. However, the nail changes persisted, and the patient was referred to a podiatrist. Aside from the observed toxicities, the patient showed partial response in the CT scan 2 months after treatment, and the serum CA19-9 decreased to a normal level.
In November 2021, the patient suffered from nasal congestion and rash/erythema with induration over the right shin, which responded to topical steroids. Two weeks later, the patient reported abdominal discomfort and mild constipation. Thus, the decision was made to introduce a phosphate binder. A CT scan in January 2022 (6 months of treatment) showed stable disease, with a mild increase in the liver and pulmonary metastases. The serum CA19-9 increased to 161 U/mL. At the same time, the painless toenail changes were persistent, and the patient reported a painful heel during walking, suggestive of plantar fasciitis. Dermatological review noted diffuse destruction of the toenails with onycholysis and subungual haematoma; the fingernails presented with distal onycholysis only (Figure 2). Due to the persistent nail changes, a 2-week treatment break was decided, and pemigatinib was continued at a reduced dose of 9 mg. Following the re-initiation of pemigatinib, the patient reported improved plantar fasciitis; however, nail discolouration worsened. The serum CA19-9 has dropped to 74 from 240 U/mL. A CT scan on 28 February 2022 showed stable disease.
One week after the CT scan, the patient reported grade 2/3 generalized abdominal pain and persistent nail discolouration. Thus, a 3-week break was commenced, leading to the resolution of abdominal pain but with ongoing nail changes. Pemigatinib 9 mg was restarted, and a CT scan in May 2022 showed stable pulmonary metastasis and a decrease in the size of hepatic metastases. Nonetheless, the patient reported heartburn and nizatidine was initiated. The patient then continued pemigatinib, with a supportive H2 blocker, an antidiarrhoeal agent and emollients. In August 2022, the patient showed improved nail changes with no signs of infection and stable grade 1 diarrhoea. A CT scan in September 2022 showed multifocal progression in the known hepatic and lung disease with new nodal and lung metastasis, and pemigatinib was discontinued, leading to a duration of benefit of 14 months. During pemigatinib therapy, the patient was able to maintain routine daily activities as most related toxicities were grade 1 or 2.