Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial
Mené sur 449 patients atteints d'une leucémie myéloïde chronique ou d'une leucémie lymphoblastique aiguë Ph+, cet essai de phase II évalue l'efficacité sur le long terme, du point de vue du taux de réponse cytogénétique et du taux de réponse moléculaire, et la toxicité du ponatinib après l'échec de plusieurs lignes thérapeutiques (durée médiane de suivi : 56,8 mois)
Ponatinib continued to provide deep, durable responses in heavily pretreated patients with chronic-phase chronic myeloid leukemia.Tolerability was acceptable in this heavily pretreated population with 5 years of follow up. Ponatinib has potent activity against native and mutant BCR-ABL1, including BCR-ABL1T315I. The pivotal phase 2 PACE trial evaluated efficacy and safety of ponatinib at a starting dose of 45 mg once daily in 449 patients with chronic myeloid leukemia (CML) or Philadelphia chromosome–positive acute lymphoblastic leukemia resistant/intolerant to dasatinib or nilotinib, or with BCR ABL1T315I. This analysis focuses on chronic-phase CML (CP-CML) patients (n=270) with 56.8-month median follow-up. Among 267 evaluable patients, 60%, 40%, and 24% achieved major cytogenetic response (MCyR), major molecular response (MMR), and MR4.5, respectively. The probability of maintaining MCyR for 5 years was 82% among responders. Dose reductions were implemented in October 2013 to decrease the risk of arterial occlusive events; ≥90% of CP-CML patients who had achieved MCyR or MMR maintained response 40 months after elective dose reductions. Estimated 5-year overall survival was 73%. In CP-CML patients, the most common treatment-emergent adverse events were rash (47%), abdominal pain (46%), thrombocytopenia (46%), headache (43%), dry skin (42%), and constipation (41%). The cumulative incidence of arterial occlusive events in CP-CML patients increased over time to 31%, while the exposure-adjusted incidence of new arterial occlusive events (15.8 and 4.9 per 100 patient-years in Years 1 and 5, respectively) did not increase over time. These final PACE results demonstrate ponatinib provides durable and clinically meaningful responses, irrespective of dose reductions, in this population of heavily pretreated CP-CML patients. This trial was registered at www.clinicaltrials.gov as NCT01207440.
Blood 2018