Nilotinib superior to imatinib in older patients with CML in chronic phase

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NEW ORLEANS—Nilotinib has superior safety and efficacy over imatinib in older patients with chronic myeloid leukemia in chronic phase, according to research presented at the Oncology Nursing Society (ONS) 37th Annual Congress.

Although chronic myeloid leukemia (CML) affects all ages, median age at diagnosis is 65 years. Physiological changes that naturally occur with aging may affect treatment response, including efficacy and side effects, in the elderly. Nilotinib is a potent, highly selective BCR-ABL kinase inhibitor approved for adults with newly diagnosed CML in chronic phase (CML-CP) and those with imatinib-resistant or -intolerant CML-CP and CML in accelerated phase (AP).

In the phase 3 ENESTnd (Evaluating Nilotinib Efficacy and Safety in clinical Trials of newly diagnosed Philadelphia chromosome–positive CML patients) study, researchers led by Gerry Gorospe, RN, BSN, PHN, MSN, Division of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, compared the efficacy and safety of nilotinib to imatinib in patients with CML-CP at 217 centers in 35 countries.

In ENESTnd, 846 patients were randomized to nilotinib 300 mg 2 times a day (n=282), nilotinib 400 mg 2 times a day (n=281), or imatinib 400 mg once a day (n=283) (median age: nilotinib arms, 47 years; imatinib, 46 years); 99 patients 65 years or older (n=36, nilotinib 300 mg; n=28, nilotinib 400 mg; n=35, imatinib) were analyzed for efficacy. Efficacy was determined by rates of complete cytogenetic response (CCyR), major molecular response (MMR; 3-log reduction in BCR-ABL transcripts), and disease progression, by age group (<65 vs ≥65 years). Safety data were also evaluated.

By 24 months, rates of CCyR and MMR in patients 65 years or older were highest in the nilotinib 300-mg arm, and comparable to those in patients younger than 65 years old. No older patient progressed to AP/blast crisis on nilotinib.

Nilotinib was generally well tolerated, and biochemical laboratory abnormalities were generally mild, transient, and manageable. Discontinuations due to adverse events or laboratory abnormalities in patients 65 years of age or older were 6%, 36%, and 17% with nilotinib 300 mg twice a day, nilotinib 400 mg twice a day, and imatinib, respectively. Two patients (one each on nilotinib 400 mg and imatinib) discontinued the study due to acute pancreatitis.

The frequency of grade ¾ cytopenias was low in patients 65 years of age or older treated with nilotinib, regardless of dose. In the nilotinib arm, no patient aged 65 years or older had grade ¾ neutropenia and only 1 patient 65 years or older reported grade ¾ anemia or thrombocytopenia. Among the 12 patients aged 65 years or older with grade ¾ hyperglycemia (8 on nilotinib 300 mg, 4 on nilotinib 400 mg), 9 patients had type 2 diabtetes at baseline. Regardless of age, no patient discontinued due to hyperglycemia.

QTcF increases greater than 60 msec were not observed in patients 65 years or older. QTcF prolongation greater than 500 msec did not occur in any patient treated with nilotinib, nor did any absolute reduction in LVEF of greater than 15%. Five cases of ischemic heart disease were reported in patients aged 65 years or older (1 [3%] each on imatinib and nilotinib 300 mg and 3 [12%] on nilotinib 400 mg) and 7 cases in patients less than 65 years of age (4 [2%] on nilotinib 300 mg and 3 [1%] on nilotinib 400 mg. Four patients 65 years or older died during the study: two on nilotinib 300 mg (1 during treatment and the other longer than 28 days after discontinuation of treatment); and 1 each on nilotinib 400 mg and imatinib longer than 28 days after discontinuing treatment. No sudden deaths were reported.

The highest rate of major molecular response was achieved by patients treated with nilotinib 300 mg twice a day, regardless of age. No patient 65 years or older experienced progression during treatment with either dose of nilotinib, despite most (94%) having intermediate or high Sokal risk scores. One patient aged 65 years or older with an intermediate Sokal risk score progressed to AP/BC on imatinib. More patients overall progressed to advanced disease with imatinib than with nilotinib.

In older patients, nilotinib 300 mg 2 times a day demonstrated higher rates of CCyR and MMR and lower rates of disease progression than imatinib, supporting its use in older patients. Nilotinib was well tolerated.

The study received funding from Novartis Pharmaceuticals Corporation.

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