Drug products: Glivec®, Imatinib Accord, Imatinib Actavis Group, Imatinib Cipla, Imatinib Fresenius Kabi, Imatinib Grindeks, Imatinib Krka d.d., Imatinib Mylan, Imatinib Sandoz, Imatinib STADA, Imatinib Teva, Imatinib Zentiva
ATC code: L01EA01
Substances: imatinib, imatinib mesylate
Female sex is correlated with better outcome of cancer diseases treated with imatinib. Side effects are more common in women, but one study reported a higher risk of renal impairment in men. There is no experience with imatinib during pregnancy, but the mechanism of action suggests a significant risk to the fetus and its use should therefore be avoided.
Differences in sex-specific incidence (higher in men) and prognosis (better in women) have been recognized for both chronic myeloid leukemia (CML) [1, 2] and gastrointestinal stromal tumor (GIST) [3, 4].
No sex differences on imatinib pharmacokinetics have been observed . Imatinib pharmacokinetics in men (n=83) and women (n=64) with GIST were comparable .
Chronic myeloid leukemia (CML)
A retrospective cohort study on 90 men and 76 women who had been treated with imatinib for CML revealed that the patient’s sex was associated with molecular response in favor of women. Men had a lower major molecular response (MMR) rate than women (63% vs. 82%) and a shorter time to relapse (median 354 days vs. 675 days) . The relationship between factors including the patient’s sex on molecular response to imatinib in CML patients (142 men, 93 women) indicated a better response in women. MMR was achieved in 77% of the women, and 55 % of men .De novo imatinib-treated CML patients (240 men, 183 women) were examined after 8 years treatment. Higher proportion of women than men had achieved undetectable BCR-ABL1 (54% vs 27%). The phenomenon was tentatively attributed to pharmacokinetic differences, immune response or simply to a better adherence in women over the long-term .The impact of sex in terms of response rates and long-term outcome observed in a series of chronic phase CML patients (114 men, 94 women) treated with imatinib as first line therapy. At 7 years control, the overall survival- and event-free survival rates for women were 84% and 73%, compared to 79% and 57% in men .BCR-ABL1 transcript levels in patients with chronic phase CML (157 men, 125 women) who received imatinib as first-line therapy followed by dasatinib or nilotinib if treatment with imatinib failed, were studied. Higher transcript levels at 3 months were associated with worse outcome measures. Rates of MMR and complete molecular response were higher in women. Relative risks for both MMR and CMR were better for (1.7 for MMR and 6.4 for CMR) .A retrospective analysis of data in three US cancer databases conducted to study survival rates in CML patients (9879 men[AF4] , 7290 women) with different ethnicities. Three-year relative survival rates of CML patients had improved significantly in the post-imatinib ( years 2002 – 2008) compared to the pre-imatinib (years 1973 – 2000) era from 43% to 65%. In the post-imatinib era, the highest rate of three-year relative survival observed among young (<50 y) Caucasian women (90%), and the lowest survival observed among older African-American men (52%).
Gastrointestinal stromal tumor (GIST)
A population-based nationwide study on Dutch GIST-patients (945 men, 804 women) showed a significant improvement in the relative survival over time in the imatinib era. The 5-year relative survival rate increased from 71 % in 2001–2004 to 81 % in 2009–2012. The 5-year relative response rates were marginally higher for women than men.A French study, which solely included patients with metastatic disease (n=434) who were started on imatinib, showed that 5-year survival benefit was greater in women (77 %, vs 54 % in men) .Studying 2986 Taiwanese GIST patients diagnosed from 1998 to 2008 showed that the 5-year overall survival rate was higher for women than men (74% vs 60%). The significant sex-difference in overall survival applied both in and before imatinib era .
CML patients (n=832) who were treated for a median of 5.8 years were enrolled in a study to assess morbidity and mortality. A total of 830 nonserious adverse events were observed in 53% of the patients. As expected, patients developed the known side effects of imatinib, including edema, muscle cramps, and gastrointestinal disturbances (diarrhea and abdominal pain or distention). The proportion of patients with at least one nonserious adverse event increased from 34% (at 6-year control) to 53% (at 8-year control). The incidence rate was lower in men, with a hazard ratio of 0.71 .According to a retrospective analysis on CML patients treated with TKI, first line imatinib therapy (225 men, 135 women) was significantly associated with chronic renal injury. The event free rate at 3 years was 55%. The risk of chronic renal adverse event (defined as a significant reduction in eGFR) and chronic kidney disease were significantly higher in men[AF7] . The HR for the onset of chronic renal adverse event in men compared to women was 1.4, and the HR for onset of chronic kidney disease in men compared to women was 4.5) .
Imatinib can cause fetal harm. It is recommended that women of childbearing potential treated with imatinib use effective contraception during and for 15 days after the treatment . Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Date of litterature search: 2022-05-18
Reviewed by: Pauline Raaschou, Diana Rydberg
Approved by: Karin Schenck-Gustafsson