SPRYCEL or Higher-Dose Imatinib Trial (START-R)

Study Design

Randomised, international, open-label, phase II study of patients with chronic phase chronic myeloid leukaemia (CML) resistant to imatinib (400-600 mg/day). Patients were randomised on a 2:1 basis to SPRYCEL 140 mg (70 mg BID)* or imatinib 800 mg (400 mg BID).

Primary Endpoint: Major cytogenetic response (MCyR).

START-R: Efficacy²⁴

• At 2 years, MCyR occurred more often in the SPRYCEL arm (53%) than in the imatinib arm (33%)
• 44% of the patients had a CCyR in the SPRYCEL arm, compared to 18% in the imatinib arm

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Time to Treatment Failure²⁴

• 72% of patients randomised to SPRYCEL remained on their allocated initial medical treatment after a median follow-up of 15 months (range: 1-21 months)
• The median time to treatment failure was not reached for SPRYCEL and was 3.5 months for imatinib

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Efficacy by Baseline BCR-ABL Mutational Analysis^†24

Of the 52 patients with BCR-ABL mutations at baseline, 46% achieved MCyR with SPRYCEL vs. 27% with imatinib (P=0.282).^†,24

• ^*The dosage used in these studies is not recommended any longer for this patient population in the EU. The recommended starting dosage in the EU for chronic phase CML has been optimised to a 100 mg once-daily regimen, reflecting a more favourable safety profile with comparable efficacy.¹
• ^†To avoid potential bias, patients with known specific BCR-ABL mutation (with high resistance to imatinib) prior to study entry were excluded: L248V, G250E, Q252H/R, Y253H/F, E255K/V, T315I/D, F317L, H396P/R.
• ^‡Twelve of 150 patients had no mutational analysis performed at baseline (dasatinib 9, imatinib 3).

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START-R: Safety²⁴

After a median follow-up of 15 months, the safety profile of both drugs was consistent with those of prior studies.

• Discontinuation due to drug intolerance was similar for SPRYCEL (16%) and high-dose imatinib (18%)

Nonhaematologic Adverse Events²⁴

Nonhaematologic adverse events were mainly mild to moderate (grade 1 or 2) and resolved spontaneously or with supportive care.

• SPRYCEL: the most common events were headache, diarrhoea, nausea, fatigue, and dyspnoea
• High-dose imatinib: the most common events were diarrhoea, fatigue, nausea, and vomiting
• Fluid retention
  • More common with high-dose imatinib (45% vs. 30%)
  • High-dose imatinib: primarily superficial oedema
  • SPRYCEL: pleural effusions, 4% grade 3 or 4
    • Best managed with early identification, temporary dose interruption, diuretics and/or pulse steroids, and dose reduction

Haematologic Adverse Events²⁴

Myelosuppression was more common with SPRYCEL.

• Grade 3 or 4 neutropenia (61% vs. 39%), thrombocytopenia (56% vs. 14%)
• Usually reversible and managed by:
  • Dose reduction or temporary interruption
  • Transfusions of packed cells (23% vs. 12%) and platelets (14% vs. 0%)

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