medwireNews: Dasatinib has durable efficacy and manageable toxicity in the long-term treatment of patients with chronic-phase chronic myeloid leukaemia (CML) that is resistant or intolerant to imatinib, shows final analysis of the CA180-034 trial.

With a minimum follow-up of 7 years, this analysis represents the longest evaluation of a second-generation tyrosine kinase inhibitor (TKI) in the second line, say lead author Neil Shah, from UCSF School of Medicine in San Francisco, California, USA, and colleagues.

In this phase III dose optimisation trial, 670 patients with imatinib-resistant or intolerant disease were randomly assigned to receive dasatinib as per one of four schedules: 100 mg/day, 50 mg twice daily, 140 mg/day or 70 mg twice daily.

Overall, 19% remained on the study treatment at the 7-year follow-up. A higher proportion of patients in the 100 mg/day arm than in the other arms continued dasatinib treatment for at least 7 years, at 22% compared with 19% each in the 50 mg and 70 mg twice daily groups and 15% in the 140 mg/day group.

Rates of major molecular response (BCR–ABL1 ≤0.1%) at 7 years were comparable across dosage schedules, as were 7-year overall survival (OS) and progression-free survival rates.

Of note, the researchers found that molecular response at 3 and 6 months was indicative of long-term prognosis. For instance, in the 100 mg/day group, the 7-year OS rates were 72% and 56% for patients with BCR–ABL1 transcript levels no higher than 10% versus above this cutoff at 3 months, a significant difference.

Dasatinib 100 mg/day, which is the dose currently approved by the US Food and Drug Administration, was “better tolerated” than the other regimens, says the team. Over a third (38%) of patients in the 100 mg/day group maintained their assigned dose, compared with the corresponding rates of 19%, 24% and 9% of patients in the 50 mg twice daily, 140 mg/day and 70 mg twice daily arms.

The cumulative rates of drug-related pleural effusion increased over time, but tended to be lower in patients given the 100 mg/day dose than those given the other doses, with 7-year rates of 28% versus 35%. Shah et al caution that “[a]s pleural effusion may occur for the first time in dasatinib-treated patients even after years of treatment, monitoring for these symptoms should continue.”

Cumulative rates of drug-related pulmonary hypertension and pulmonary arterial hypertension remained low (≤3% across all doses) during the follow-up, as did the incidence of cardiovascular adverse events (≤4% across all doses).

Furthermore, no new safety signals emerged during this analysis, the study authors report.

They conclude in the American Journal of Hematology that “[l]ong-term follow-up data presented here confirm the 6-month, 2-year, and 6-year results of a positive benefit/risk associated with long-term dasatinib use at its approved dose of 100 mg [once daily]” in this patient population.

By Shreeya Nanda, Senior medwireNews Reporter

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