FDA D.I.S.C.O. Burst Edition: FDA approvals of Jaypirca (pirtobrutinib) for relapsed or refractory mantle cell lymphoma, and Orserdu (elacestrant) for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer
Regulatory news: On Jan 27, 2023, the FDA granted accelerated approval to pirtobrutinib (Jaypirca) for relapsed or refractory mantle cell lymphoma after ≥2 prior systemic therapies including a BTK inhibitor, based on the single-arm BRUIN trial (ORR 50%, CR 13%, median DOR 8.3 months). The FDA also approved elacestrant (Orserdu) for postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced/metastatic breast cancer after ≥1 endocrine therapy line, supported by EMERALD (ESR1-mutated median PFS 3.8 vs 1.9 months).
FDA D.I.S.C.O. Burst Edition (Jan 27, 2023): Two oncology drug approvals (regulatory approval)
Pirtobrutinib (Jaypirca) received FDA accelerated approval for relapsed or refractory mantle cell lymphoma after at least two prior lines of systemic therapy, including a BTK inhibitor.
Evidence: BRUIN, an open-label, multicenter, single-arm trial of pirtobrutinib monotherapy in 120 patients previously treated with a BTK inhibitor (median 3 prior lines; 93% had ≥2 lines; 83% discontinued prior BTK inhibitor due to refractory/progressive disease). Dose: 200 mg orally once daily until progression or unacceptable toxicity. Primary efficacy measures: ORR and DOR (IRC, Lugano). Results: ORR 50%, CR 13%; median DOR 8.3 months; 6-month DOR rate 65.3%.
Safety: Common adverse reactions (>15%): fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, bruising. Grade 3/4 lab abnormalities (>10%): decreased neutrophils, lymphocytes, platelets. Label warnings/precautions include infections, hemorrhage, cytopenias, atrial fibrillation/flutter, and second primary malignancies.
Elacestrant (Orserdu) was FDA approved for postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced/metastatic breast cancer after progression on ≥1 line of endocrine therapy. FDA also approved Guardant360 CDx as a companion diagnostic.
Evidence: EMERALD (randomized, open-label, active-controlled; n=478, including 228 with ESR1 mutations). In ESR1-mutated patients, median PFS 3.8 vs 1.9 months (elacestrant vs fulvestrant or aromatase inhibitor). An exploratory analysis in ESR1–wild-type patients showed HR 0.86, suggesting the ITT benefit was primarily driven by the ESR1-mutated subgroup.