Pregnancies during and after trastuzumab and/or lapatinib in patients with human epidermal growth factor receptor 2–positive early breast cancer: Analysis from the NeoALTTO (BIG 1‐06) and ALTTO (BIG 2‐06) trials

Abstract

Background Limited data exist on the safety of using anti–human epidermal growth factor receptor 2 (HER2) targeted agents during pregnancy. To date, only retrospective studies have assessed the prognosis of patients with a pregnancy after prior early breast cancer, with no data in HER2‐positive patients. Methods The Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization (NeoALTTO) trial and the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO) trial were randomized phase 3 trials for patients with HER2‐positive early breast cancer. In both trials, pregnancy information was prospectively collected. Pregnancy outcomes were compared between patients unintentionally exposed to trastuzumab and/or lapatinib during gestation (the exposed group) and those who became pregnant after trastuzumab and/or lapatinib completion (the unexposed group). In the ALTTO trial, disease‐free survival (DFS) was compared between pregnant patients and those aged 40 years or younger without a subsequent pregnancy via an extended Cox model with time‐varying covariates to account for a guarantee‐time bias. Results Ninety‐two patients (12 in the exposed group and 80 in the unexposed group) had a pregnancy: 7 in the NeoALTTO trial and 85 in the ALTTO trial. Seven patients (58.3%) in the exposed group and 10 patients (12.5%) in the unexposed group opted for an induced abortion; in the unexposed group, 10 patients (12.5%) had a spontaneous abortion. No pregnancy/delivery complications were reported for the remaining cases, who successfully completed their pregnancy, with the exception of 1 fetus with trisomy 21 (Down syndrome). No significant difference in DFS (adjusted hazard ratio, 1.12; 95% confidence interval, 0.52‐2.42) was observed between young patients with a pregnancy (n = 85) and young patients without a pregnancy (n = 1307). Conclusions For patients with HER2‐positive early breast cancer, having a pregnancy after treatment completion appears to be safe without compromising fetal outcome or maternal prognosis.

Baby steps: Pregnancy outcomes after human epidermal growth factor receptor 2–targeted therapy

“…The current study by Lambertini et al adds to our understanding of pregnancy outcomes after HER2‐targeted treatment of breast cancer. Ongoing efforts represent important attempts to advance the current knowledge.…”

“…As best as can be determined in the absence of randomized data, pregnancy after breast cancer does not increase the risk of disease recurrence, thereby reinforcing its safety irrespective of HR status. 20,21 In the study by Lambertini et al, 16 among the 80 patients in the unexposed group, the first pregnancy occurred at a median of 48.6 months after the cessation of anti-HER2 therapy, with 54 patients (67.5%) successfully completing their pregnancy (median gestational week at the time of delivery was 39 weeks). No pregnancy or delivery complications were reported.…”

“…It is worth reminding readers that “trastuzumab can cause fetal harm when administered to a pregnant woman, resulting in cases of oligohydramnios and pulmonary hypoplasia, skeletal abnormalities, and neonatal death” and that to our knowledge there are no adequate and well‐controlled studies to date regarding treatment with lapatinib in pregnant women. Thus, despite the reassuring findings of Lambertini et al, women should be advised that anti–HER2‐targeted treatment is not recommended during pregnancy, irrespective of the trimester. It is important to reinforce the need for the use of adequate contraception to young patients with breast cancer during and after an appropriate period after the completion of HER2‐targeted therapy.…”

“…Temporary ovarian suppression during chemotherapy with gonadotropin‐releasing hormone (GnRH) agonists such as goserelin or leuprolide has shown some promise as a way to decrease the incidence of chemotherapy‐induced ovarian failure . However, in their study, Lambertini et al did not describe the use of GnRH agonists during experimental chemotherapy in the NeoALLTO and ALLTO studies, although adjuvant use was mentioned. Thus, we cannot make any additional conclusions regarding the impact of GnRH agonists in this setting.…”

Fertility, sexuality and cancer in young adult women

“…Despite on-going concerns among patients and physicians regarding the possibility of pregnancy following anticancer therapies [9,10], in recent years, several studies have provided reassuring evidence on the lack of severe complications and detrimental consequences for both the mother and the baby [11][12][13][14], including in the cases of hormone receptor-positive breast cancer [15]. Therefore, reducing the risk of treatment-related POI is of high priority in this setting.…”