Neratinib Tablets

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Diarrhea [see WARNINGS AND PRECAUTIONS]
• Hepatotoxicity [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure of NERLYNX as a single agent in ExteNET, a multicenter, randomized, double-blind, placebo-controlled study of NERLYNX within 2 years after completion of adjuvant treatment with trastuzumab-based therapy in women with HER2positive early-stage breast cancer. Patients who received NERLYNX in this trial were not required to receive any prophylaxis with antidiarrheal agents to prevent the NERLYNX-related diarrhea. The median duration of treatment was 11.6 months in the NERLYNX arm and 11.8 months in the placebo arm. The median age was 52 years (60% were ≥ 50 years old, 12% were ≥ 65 years old); 81% were Caucasian, 3% Black or African American, 14% Asian and 3% other. A total of 1408 patients were treated with NERLYNX.

NERLYNX dose reduction due to an adverse reaction of any grade occurred in 31.2% of patients receiving NERLYNX compared to 2.6% of patients receiving placebo. Permanent discontinuation due to any adverse reaction was reported in 27.6% of NERLYNX-treated patients. The most common adverse reaction leading to discontinuation was diarrhea, accounting for 16.8% of NERLYNX-treated patients.

The most common adverse reactions ( > 5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, weight decreased and urinary tract infection. The most frequently reported Grade 3 or 4 adverse reactions were diarrhea, vomiting, nausea, and abdominal pain.

Serious adverse reactions in the NERLYNX arm included diarrhea (1.6%), vomiting (0.9%), dehydration (0.6%), cellulitis (0.4%), renal failure (0.4%), erysipelas (0.4%), alanine aminotransferase increased (0.3%), aspartate aminotransferase increased (0.3%), nausea (0.3%), fatigue (0.2%), and abdominal pain (0.2%).

Table 6 summarizes the adverse reactions in ExteNET.

Table 6: Adverse Reactions Reported in ≥ 2% of NERLYNX-Treated Patients in ExteNET