MO01.04 Management of Selected Adverse Events With Capmatinib: Institutional Experiences From the GEOMETRY Mono-1 Trial

Capmatinib is approved in the United States and Japan for adults with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to MET exon 14 skipping (METex14), based on results from the Phase II GEOMETRY mono-1 trial (NCT02414139). The most common adverse reactions (≥20%) were peripheral edema, nausea, fatigue, vomiting, dyspnea, and decreased appetite. Here, we describe the management of peripheral edema, nausea, and vomiting experienced by patients receiving capmatinib across two institutions in the United States. In GEOMETRY mono-1, patients received capmatinib tablets at a dose of 400 mg twice daily. Dose reductions in 100-mg steps to a minimum dose of 200 mg twice daily were required for adverse events of grade ≥3. Grade 3 adverse events of nausea or peripheral edema required withholding capmatinib until resolved to grade ≤1, then dose reducing one level. Grade 2 vomiting required withholding capmatinib until resolved to grade ≤1; grade ≥3 and recurrent grade 2 required withholding capmatinib until resolution to grade ≤2 and grade ≤1, respectively, and dose reducing one level. Across two institutions, patients received capmatinib 400 mg twice daily as a first-line or second-line therapy for the treatment of NSCLC with METex14 as part of the GEOMETRY mono-1 study. Patients taking capmatinib commonly experienced mild (grade 1) peripheral edema. Peripheral edema was generally managed with compression stockings, elevation of affected limbs, and/or diuretics. At one institution, patients were referred to a lymphedema clinic; these patients were managed with lymphatic massage, prescription-grade compression stockings, and/or stretching exercises. Stretching exercises and compression stockings (20-30 mm Hg) improved grade 1 bilateral lower edema without discontinuation of capmatinib treatment. In general, bilateral lower edema resolved with discontinuation of capmatinib. Patients sometimes experienced nausea and vomiting when taking capmatinib while fasted. Methods for treating nausea or vomiting included as-needed antiemetics and premedication with a phenothiazine or 5-HT3 antagonist. Some patients reported reduced nausea when capmatinib was taken after eating, and others experienced reduced vomiting after reducing capmatinib dosage to 300 mg twice daily. Across two institutions, patients treated with capmatinib who experienced peripheral edema, nausea, and vomiting were generally managed successfully. In some cases, compression stockings improved peripheral edema. In our experience, taking capmatinib with food reduced nausea and vomiting.