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Cancer
Published in Vincenzo Berghella, Maternal-Fetal Evidence Based Guidelines, 2022
Elyce Cardonick, Charlotte Maggen, Puja Patel
Birth control should be strongly advised while survivors are taking tamoxifen and trastuzumab. There have been case reports of ambiguous genitalia and Goldenhar syndrome in children exposed to tamoxifen in utero [163, 164]. Animal studies show rib abnormalities, metaplastic and dysplastic changes in the epithelium of the uterus and reproductive tract similar to DES, growth restriction, and death [164–166]. A recent literature review reported an increased incidence of fetal abnormalities following prenatal exposure to tamoxifen (12.6% vs. 3.9% in the general population), however no causal relationship could be established [167]. As a consequence, the authors suggest that the use of tamoxifen during pregnancy should not be absolutely contraindicated and patients should be counseled on disadvantages of both discontinuing or postponing treatment. Pregnancies exposed to trastuzumab have been complicated by reversible oligohydramnios and fetal renal insufficiency [50–55, 168, 169]. Trastuzumab is able to cross the placenta by active transport from the second trimester of pregnancy onwards. For women who become accidentally pregnant while taking trastuzumab and wish to continue pregnancy, trastuzumab should be stopped and pregnancy could be allowed to continue.
Chemotherapy in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Trastuzumab is an antibody indicated for the treatment of patients with HER2 overproducing breast cancers. The antibody exerts its effect on cancer cells both by activating the body’s immune response against the cells and by shutting down the signal that tells the cancer cells to grow and divide uncontrollably. Trastuzumab was given to six pregnant patients for the treatment of breast cancer. Anhydramnios developed in three out of the six patients treated (97). Another patient with recurrent metastatic breast cancer was treated with trastuzumab for the first 23 weeks of an undiagnosed pregnancy (98). The patient was delivered by cesarean section at 27 weeks due to severe vaginal bleeding. This pregnancy was also noted to have oligohydramnios. The infant was noted to have uncommonly strong capillary leak syndrome, persisting infections, and necrotizing enterocolitis. The baby died due to multiple organ failure 21 weeks after delivery. Other patients have received trastuzumab in the second and third trimesters without complication to the fetus (96).
Antibody-Based Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The most common side effects associated with trastuzumab include infusion-related fever and chills, pain, asthenia, nausea, vomiting, headache, and possible hypersensitivity reactions, such as anaphylaxis, urticaria, and angioedema. Cardiotoxicity, pulmonary events, and GI disturbances can also occur, along with chest pain, hypotension, and pulmonary events, which are sometimes delayed. As mentioned above, concomitant use of trastuzumab with anthracyclines is associated with cardiotoxicity and should be avoided if possible. Cardiac function should be carefully monitored if co-administration is necessary, and caution should be exercised in patients with coronary heart disease, history of hypertension, coronary artery disease, and uncontrolled arrhythmias and severe dyspnea at rest. Several less serious side effects have also been reported including taste disturbance and alopecia. Trastuzumab should not be given in pregnancy unless potential benefits outweigh risks, and breastfeeding should be avoided during treatment and for six months afterwards.
A systematic review of clinical trials of treatment regimens in HER2-amplified metastatic colorectal cancer
Published in Expert Review of Anticancer Therapy, 2023
Daniel Sur, Cristina Lungulescu, Elena Adriana Dumitrescu, Vlad Afrăsânie, Ștefan Spînu, Cristian Virgil Lungulescu, Hans- Joachim Schmoll
The most common treatment-related adverse events (AEs) of chemotherapy (capecitabine) in combination with lapatinib were fatigue (83%), hand-foot syndrome (69%), and diarrhea (59%). Lapatinib in combination with trastuzumab often caused diarrhea (78%), rash (48%), and fatigue (48%). In the FOCUS4-D trial skin rash occurred in 20% of the AZD8931 group versus none in the placebo group, and diarrhea occurred in 7% of the AZD8931 group versus 6% in the placebo group. The combination of trastuzumab and pertuzumab frequently caused fatigue (32%), diarrhea (34%), nausea (30%) in My-Pathway study, while the TRIUMPH trial found that infusion-related events, diarrhea, stomatitis, and malaise were the most common side effects. Trastuzumab-deruxtecan (T-DXd), an antibody–drug conjugate, was associated with a high incidence of nausea (60%), fatigue (33%), and diarrhea (28%), while ado-trastuzumab-emtansine (T-DM1) combined with pertuzumab-induced fatigue (18%), hyperbilirubinemia (9%), and thrombocytopenia (8%). Summaries of each of the seven papers included in this study are presented in Table 2.
Management of breast cancer diagnosed during pregnancy: global perspectives
Published in Expert Review of Anticancer Therapy, 2022
Jyoti Bajpai, Rima Pathak, T.S. Shylasree, Hope S. Rugo
In contrast to chemotherapy, owing to its molecular weight, trastuzumab’s placental transfer is minimal during the first trimester but increases from the second trimester onwards and is associated with oligo/anhydramnios and premature delivery. Trastuzumab is not recommended during pregnancy due to substantial risks involved, however, it may be carefully discussed in special high-risk situations weighing fetal and maternal risks and benefits [36]. However, in the HERA trial, a few women who accidentally conceived while receiving trastuzumab delivered healthy neonates [31,35]. Inadvertent fetal exposure to 1 to 2 cycles of trastuzumab therapy is not a strong reason for termination of pregnancy.There is lack of data about pertuzumab and hence it should be avoided. Figure 1A shows the management algorithm.
Immunotherapy for Bladder Cancer: Latest Advances and Ongoing Clinical Trials
Published in Immunological Investigations, 2022
Daniela F. Ward Grados, Hamed Ahmadi, Thomas S Griffith, Christopher A. Warlick
Several targets are being explored for the development or repurpose of ADCs for the treatment of BC. Human epidermal growth factor 2 (HER2) is a commonly expressed antigen throughout several solid malignancies. Trastuzumab, a mAb specific for HER2, is widely used to treat HER2+ breast cancer. A recently published metanalysis by Gan et al. stated a significant correlation between HER2 expression and different stages of BC (from CIS to metastatic BC), suggesting HER2 could be an ideal target for BC treatment (Gan et al. 2021). Trastuzumab-emtansine is an ADC already approved as a treatment for patients with HER2+ breast cancer who have failed therapy with trastuzumab and taxanes (Gan et al. 2021). NCT02675829 is an ongoing trial evaluating the use of trastuzumab-emtansine in several different HER2+ solid tumors, including bladder cancer.