Contributions
Abstract: EP671
Type: E-Poster Presentation
Session title: Chronic myeloid leukemia - Clinical
Background
Bosutinib is approved for patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML), at a starting dose of 400 mg once daily (QD) in newly diagnosed patients in chronic phase (CP).
Aims
This analysis evaluated the impact dose reduction has on the outcomes of bosutinib and imatinib in patients with CP CML.
Methods
In the open-label BFORE trial, 536 patients with newly diagnosed CP CML were randomized to receive 400 mg QD bosutinib (N=268) or imatinib (N=268; 3 untreated). Dose could be reduced to 300 mg QD for toxicity. Following sponsor approval, dose reduction to bosutinib 200 mg QD was permitted for 4 weeks maximum; after this time, dose escalation or treatment discontinuation was required. Maintenance of response after dose reduction was defined as having a response >6 months after the first reduction. Database lock: June 12, 2020, 5 years after the last patient enrolled.
Results
In the bosutinib arm, dose reduction to 300 (without further reduction) or 200 mg QD was seen in 82 (31%) and 33 (12%) patients, and median time to dose reduction was 85 and 205 days. In the imatinib arm, 50 (19%) patients had a dose reduction to 300 mg QD, and median time to dose reduction was 92 days. Most common (≥2% of patients) treatment-emergent adverse events (TEAEs) leading to dose reduction were increased alanine aminotransferase (8%), thrombocytopenia (7%), diarrhea (7%), increased lipase (6%), increased aspartate aminotransferase (4%), nausea (4%), neutropenia (3%), rash (3%) and abdominal pain (2%) with bosutinib, and neutropenia (4%) with imatinib.
Of the patients who remained on 400 mg QD bosutinib (n=153) or imatinib (n=214), respectively, 120 (78%) and 139 (65%) achieved major molecular response (MMR). Among patients who had a bosutinib dose reduction to 300 mg QD, 51/82 (62%) had MMR >6 months after dose reduction: 14 (17%) maintained MMR before and after dose reduction and 37 (45%) achieved MMR for the first time after dose reduction. Seven (9%) patients had MMR before dose reduction but discontinued treatment before the next >6 months assessment. In the imatinib arm, 32/50 (64%) patients had MMR >6 months after dose reduction: 9 (18%) maintained MMR before and after dose reduction and 23 (46%) achieved MMR for the first time after dose reduction. One (2%) patient had MMR before dose reduction but discontinued treatment before the next >6 months assessment and 1 (2%) patient lost a previously attained MMR after dose reduction. Among patients who had a bosutinib dose reduction to 200 mg QD, 12/33 (36%) had MMR >6 months after dose reduction: 7 (21%) maintained MMR before and after dose reduction and 5 (15%) achieved MMR for the first time after dose reduction. Six (18%) patients had MMR before dose reduction but discontinued treatment before the next >6 months assessment. Similar trends were seen for complete cytogenetic response.
Conclusion
Management of TEAEs through bosutinib or imatinib dose reduction enabled patients to continue treatment, with a substantial number of patients achieving MMR for the first time after dose reduction.
Keyword(s): Chronic myeloid leukemia, Clinical trial, Tyrosine kinase inhibitor
Abstract: EP671
Type: E-Poster Presentation
Session title: Chronic myeloid leukemia - Clinical
Background
Bosutinib is approved for patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML), at a starting dose of 400 mg once daily (QD) in newly diagnosed patients in chronic phase (CP).
Aims
This analysis evaluated the impact dose reduction has on the outcomes of bosutinib and imatinib in patients with CP CML.
Methods
In the open-label BFORE trial, 536 patients with newly diagnosed CP CML were randomized to receive 400 mg QD bosutinib (N=268) or imatinib (N=268; 3 untreated). Dose could be reduced to 300 mg QD for toxicity. Following sponsor approval, dose reduction to bosutinib 200 mg QD was permitted for 4 weeks maximum; after this time, dose escalation or treatment discontinuation was required. Maintenance of response after dose reduction was defined as having a response >6 months after the first reduction. Database lock: June 12, 2020, 5 years after the last patient enrolled.
Results
In the bosutinib arm, dose reduction to 300 (without further reduction) or 200 mg QD was seen in 82 (31%) and 33 (12%) patients, and median time to dose reduction was 85 and 205 days. In the imatinib arm, 50 (19%) patients had a dose reduction to 300 mg QD, and median time to dose reduction was 92 days. Most common (≥2% of patients) treatment-emergent adverse events (TEAEs) leading to dose reduction were increased alanine aminotransferase (8%), thrombocytopenia (7%), diarrhea (7%), increased lipase (6%), increased aspartate aminotransferase (4%), nausea (4%), neutropenia (3%), rash (3%) and abdominal pain (2%) with bosutinib, and neutropenia (4%) with imatinib.
Of the patients who remained on 400 mg QD bosutinib (n=153) or imatinib (n=214), respectively, 120 (78%) and 139 (65%) achieved major molecular response (MMR). Among patients who had a bosutinib dose reduction to 300 mg QD, 51/82 (62%) had MMR >6 months after dose reduction: 14 (17%) maintained MMR before and after dose reduction and 37 (45%) achieved MMR for the first time after dose reduction. Seven (9%) patients had MMR before dose reduction but discontinued treatment before the next >6 months assessment. In the imatinib arm, 32/50 (64%) patients had MMR >6 months after dose reduction: 9 (18%) maintained MMR before and after dose reduction and 23 (46%) achieved MMR for the first time after dose reduction. One (2%) patient had MMR before dose reduction but discontinued treatment before the next >6 months assessment and 1 (2%) patient lost a previously attained MMR after dose reduction. Among patients who had a bosutinib dose reduction to 200 mg QD, 12/33 (36%) had MMR >6 months after dose reduction: 7 (21%) maintained MMR before and after dose reduction and 5 (15%) achieved MMR for the first time after dose reduction. Six (18%) patients had MMR before dose reduction but discontinued treatment before the next >6 months assessment. Similar trends were seen for complete cytogenetic response.
Conclusion
Management of TEAEs through bosutinib or imatinib dose reduction enabled patients to continue treatment, with a substantial number of patients achieving MMR for the first time after dose reduction.
Keyword(s): Chronic myeloid leukemia, Clinical trial, Tyrosine kinase inhibitor