Human Data

In the post-marketing setting, treatment with trastuzumab during pregnancy has resulted in cases of oligohydramnios, some associated with fatal pulmonary hypoplasia, skeletal abnormalities and neonatal death. These case reports described oligohydramnios in pregnant women who received trastuzumab either alone or in combination with chemotherapy. In some case reports, amniotic fluid index increased after trastuzumab was stopped. In one case, trastuzumab therapy resumed after the amniotic fluid index improved, and oligohydramnios recurred.
 

Animal Data

There were no reproductive and developmental toxicology studies conducted with ado-trastuzumab emtansine. DM1, the cytotoxic component of KADCYLA, disrupts microtubule function. DM1 is toxic to rapidly dividing cells in animals and is genotoxic, suggesting it has the potential to cause embryotoxicity and teratogenicity. In studies where trastuzumab was administered to pregnant monkeys at doses up to 25 mg/kg (about 7 times the clinical dose), trastuzumab crossed the placental barrier during the early and late phases of gestation. The resulting concentrations of trastuzumab in fetal blood and amniotic fluid were approximately 33% and 25%, respectively, of those present in the maternal serum but were not associated with adverse findings.
 

8.3 Nursing Mothers
 
It is not known whether KADCYLA, specifically, is excreted in human milk, but IgG is known to be excreted in human milk. In lactating monkeys, trastuzumab was excreted in small amounts (about 0.3% of maternal serum concentrations) in breast milk after post-partum doses of 25 mg/kg (about 7 times the clinical dose of KADCYLA). Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from KADCYLA, a decision should be made whether to discontinue nursing or discontinue KADCYLA, taking into account the importance of the drug to the mother [see Warnings and Precautions (5.3)].
 

8.4 Pediatric Use
 
Safety and effectiveness of KADCYLA have not been established in pediatric patients.
 

8.5 Geriatric Use
 
Of 495 patients who were randomized to KADCYLA in the randomized trial (Study 1) [see Clinical Studies (14.1)], 65 patients (13%) were ≥ 65 years of age and 11 patients (2%) were ≥ 75 years of age. In patients ≥ 65 years old (n=138 across both treatment arms) the hazard ratios for progression-free survival (PFS) and Overall Survival (OS) were 1.06 (95% CI: 0.68, 1.66) and 1.05 (95% CI: 0.58, 1.91), respectively.
 
Population pharmacokinetic analysis indicates that age does not have a clinically meaningful effect on the pharmacokinetics of ado-trastuzumab emtansine [see Clinical Pharmacology (12.3)].
 

8.6 Females of Reproductive Potential
 
KADCYLA can cause embryo-fetal harm when administered during pregnancy. Counsel patients regarding pregnancy prevention and planning. Advise females of reproductive potential to use effective contraception while receiving KADCYLA and for 6 months following the last dose of KADCYLA.
 
If KADCYLA is administered during pregnancy or if the patient becomes pregnant while receiving KADCYLA, immediately report exposure to the Genentech Adverse Event Line at 1-888-835-2555. Encourage women who may be exposed during pregnancy to enroll in the MotHER Preg