Fourth-line bosutinib ‘appropriate’ after prior CML treatment failure, intolerance

Mar 24 2015

By Shreeya Nanda, Senior medwireNews Reporter

A Spanish study suggests that bosutinib can help improve or maintain response in patients with chronic myeloid leukaemia (CML) after treatment failure of three previous tyrosine kinase inhibitors (TKI).

Researcher Juan Luís Steegmann (Hospital Universitario de la Princesa, Madrid, Spain) and colleagues analysed medical records of 30 chronic phase CML patients with Philadelphia chromosome-positive disease given bosutinib under the Spanish Compassionate Use programme after discontinuing imatinib, dasatinib and nilotinib as a result of resistance or intolerance.

Of the 15 patients without a complete cytogenetic response at baseline, defined as after TKI use but before bosutinib initiation, two (13.3%) achieved it following bosutinib treatment.

And three (14.3%) of the 21 participants without a major molecular response and three (11.1%) of the 27 without a deep molecular response at baseline went on to achieve the respective response after receiving bosutinib.

Overall, the likelihood of maintaining or improving on the complete cytogenetic response achieved at baseline was 56.6%, and that of achieving or maintaining a major molecular response was 36.7%.

After a median follow-up of 11.5 months, median event-free survival was 11.7 months, while median progression-free survival had not been reached, with 20-month survival estimates of 63.3% and 80.0%, respectively.

When participants were stratified by the absence or presence of a complete cytogenetic response at bosutinib initiation, 20-month event-free survival estimate was 46.7% for those without and 80.0% for those with a complete cytogenetic response. And the 20-month progression-free survival estimates were 73.3% and 86.7%, respectively.

Haematological adverse events of grade 3 or 4 were more frequent in patients without than in those with a baseline complete cytogenetic response, at 33.3% versus 0.0%, the team reports in the American Journal of Hematology.

But the occurrence of grade 3 or 4 nonhaematological toxicities (such as diarrhoea and alanine transaminase/aspartate aminotransferase elevation) was comparable between the two sets of patients.

Bosutinib did not cause pleural effusions or vascular episodes in the 15 patients who had experienced pleural effusion while undergoing dasatinib therapy, nor in the 10 participants in whom vascular events had been observed during treatment with nilotinib.

Altogether three patients discontinued bosutinib as a result of adverse events.

The researchers conclude that while awaiting the results of the ongoing prospective clinical trial of fourth-line bosutinib, their case series, the “largest” to their knowledge, supports bosutinib as a “valid treatment option for fourth-line treatment of patients that are resistant or intolerant to previous TKIs.”

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