HEM/ONC News By Devon Schuyler

Ivosidenib Approved for Relapsed or The most common adverse reactions to are Refractory Acute Myeloid neutropenia, nausea, infections, fatigue, diarrhea, leuko- On July 20, the US Food and Drug Administration penia, vomiting, alopecia, headache, constipation, rash, (FDA) approved ivosidenib (Tibsovo, Agios) for adults and cough. with relapsed or refractory (AML) who have an IDH1 mutation. The FDA simulta- FDA Expands Enzalutamide Indication neously approved the RealTime IDH1 Assay (Abbott), a to Include Patients With Nonmetastatic companion diagnostic, to select candidates for treatment. CRPC The approval of ivosidenib was based on an open- On July 13, the FDA expanded the indication for enzalu- label, single-arm, multicenter that included tamide (Xtandi, Astellas) to include patients with non- 174 adults with relapsed or refractory AML and an IDH1 metastatic castration-resistant prostate cancer (CRPC). mutation. Patients received ivosidenib by mouth at a start- Enzalutamide was previously approved for use only in ing dose of 500 mg daily until disease progression, unac- patients with metastatic CRPC. ceptable toxicity, or hematopoietic stem cell transplant. The new indication is based on the results of the mul- The median duration of treatment was 4.1 months (range, ticenter PROSPER trial, in which 1401 patients were ran- 0.1-39.5 months). A total of 21 patients (12%) received a domly assigned in a 2:1 ratio to either oral enzalutamide stem cell transplant following ivosidenib treatment. or placebo once daily. Patients without a prior bilateral The rate of complete remission (CR) plus CR with orchiectomy continued to use gonadotropin-releasing partial hematologic recovery was 32.8% (95% CI, 25.8%- hormone. 40.3%). The median time to response was 2 months Metastasis-free survival was significantly longer in (range, 0.9-5.6 months), and the median duration of the enzalutamide group than in the placebo group, at response was 8.2 months (95% CI, 5.6-12 months). Of 36.6 months vs 14.7 months, respectively (hazard ratio, the 110 patients who were dependent on transfusions 0.29; 95% CI, 0.24-0.35; P<.0001). of red blood cells or platelets at baseline, 37.3% became The most common adverse reactions that occurred independent of these transfusions during any 56-day more frequently in the enzalutamide-treated group than post-baseline period. in the placebo group were asthenia/fatigue, hot flashes, The most common adverse reactions to ivosidenib hypertension, dizziness, nausea, and falls. were fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis, QT prolongation, rash, pyrexia, Additional Approvals cough, and constipation. • On July 30, the FDA approved iobenguane I 131 (Azedra, Progenics) for patients 12 years or older FDA Expands Ribociclib Indication to Include who have pheochromocytoma or paraganglioma that Premenopausal or Perimenopausal Women is iobenguane scan–positive, unresectable, locally On July 18, the FDA expanded the indication for riboci- advanced, or metastatic and who require systemic clib (Kisqali, Novartis) in combination with an aromatase anti­cancer therapy. inhibitor to include premenopausal or perimenopausal • On July 10, the FDA approved (Yervoy, women with hormone receptor–positive, human epider- Bristol-Myers Squibb) for use in combination with mal growth factor receptor 2 (HER2)–negative advanced (Opdivo, Bristol-Myers Squibb) for patients or metastatic breast cancer, as initial endocrine-based 12 years or older with microsatellite instability–high or therapy. The FDA also approved ribociclib in combina- mismatch repair–deficient metastatic colorectal cancer tion with fulvestrant (Faslodex, AstraZeneca) for post- that has progressed following treatment with a fluoro- menopausal women with hormone receptor–positive, pyrimidine, oxaliplatin, and irinotecan. HER2-negative advanced or metastatic breast cancer, as • On June 19, the FDA limited the use of initial endocrine-based therapy or following disease pro- (Tecentriq, Genentech) and (Keytruda, gression during endocrine therapy. Merck) in patients with locally advanced or metastatic Ribociclib was previously approved for use in post- urothelial cancer who are not eligible for cisplatin- menopausal women with hormone receptor–positive, containing therapy. HER2-negative advanced or metastatic breast cancer in • On June 27, the FDA approved the combination of combination with an aromatase inhibitor as initial endo- encorafenib (Braftovi, Array) and (Mek- crine therapy. The new indications for ribociclib are based tovi, Array) for patients with unresectable or meta- on the randomized, double-blind, placebo-controlled static melanoma who have a BRAF V600E or V600K MONALEESA-7 and MONALEESA-3 trials. mutation.

528 Clinical Advances in Hematology & Oncology Volume 16, Issue 8 August 2018