Erlox Adverse Reactions

Safety evaluation of erlotinib is based on the data from more than 1500 patients treated with at least one 150 mg dose of erlotinib monotherapy and more than 300 patients who received erlotinib 100 or 150 mg in combination with gemcitabine. The incidence of adverse drug reactions (ADRs) from clinical trials reported with erlotinib alone or in combination with chemotherapy are summarized by National Cancer Institute - Common Toxicity Criteria (NCI - CTC) Grade in Table 1. The listed ADRs were those reported in at least 10% (in the erlotinib group) of patients and occurred more frequently (>3%) in patients treated with erlotinib than in the comparator arm. Other ADRs including those from other studies are summarized in Table 2.
Adverse drug reactions from clinical trials (Table 1) are listed by MedDRA system organ class. The corresponding frequency category for each adverse drug reactions is based on the following convention: Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Very rare (<1/10,000); Not known (cannot be estimated from the available data.
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Non-small cell lung cancer (Erlotinib administered as monotherapy): First-Line Treatment of Patients with EGFR Mutations: In an open-label, randomized phase III study, ML20650 conducted in 154 patients, the safety of erlotinib for first-line treatment of NSCLC patients with EGFR activating mutations was assessed in 75 patients; no new safety signals were observed in these patients.
The most frequent ADRs seen in patients treated with erlotinib in study ML20650 were rash and diarrhea (any Grade 80% and 57%, respectively), most were Grade 1/2 in severity and manageable without intervention. Grade 3 rash and diarrhea occurred in 9% and 4% of patients, respectively. No Grade 4 rash or diarrhea was observed. Both rash and diarrhea resulted in discontinuation of erlotinib in 1% of patients. Dose modifications (interruptions or reductions) for rash and diarrhea were needed in 11% and 7% of patients, respectively.
Maintenance treatment: In two other double-blind, randomized, placebo-controlled Phase III studies BO18192 (SATURN) and BO25460 (IUNO); erlotinib was administered as maintenance after first-line chemotherapy. These studies were conducted in a total of 1532 patients with advanced, recurrent or metastatic NSCLC following first-line standard platinum-based chemotherapy, no new safety signals were identified.
The most frequent ADRs seen in patients treated with erlotinib in studies BO18192 and BO25460 were rash (BO18192: all grades 49.2%, grade 3: 6.0%; BO25460: all grades 39.4%, grade 3: 5.0%) and diarrhea (BO18192: all grades 20.3%, grade 3: 1.8%; BO25460: all grades 24.2%, grade 3: 2.5%). No Grade 4 rash or diarrhea was observed in either study. Rash and diarrhea resulted in discontinuation of erlotinib in 1% and <1% of patients, respectively, in study BO18192, while no patients discontinued for rash or diarrhea in BO25460. Dose modifications (interruptions or reductions) for rash and diarrhea were needed in 8.3% and 3% of patients, respectively, in study BO18192 and 5.6% and 2.8% of patients respectively, in study BO25460.
Second and Further Line Treatment: In a randomized double-blind study (BR.21; erlotinib administered as second line therapy), rash (75%) and diarrhea (54%) were the most commonly reported adverse drug reactions (ADRs). Most were Grade 1/2 in severity and manageable without intervention. Grade 3/4 rash and diarrhea occurred in 9% and 6%, respectively in erlotinib-treated patients and each resulted in study discontinuation in 1% of patients. Dose reduction for rash and diarrhea was needed in 6% and 1% of patients, respectively. In study BR.21, the median time to onset of rash was 8 days, and the median time to onset of diarrhea was 12 days.
In general, rash manifests as a mild or moderate erythematous and papulopustular rash, which may occur or worsen in sun exposed areas. For patients who are exposed to sun, protective clothing, and/or use of sun screen (e.g. mineral-containing) may be advisable.
Pancreatic cancer (Erlotinib administered concurrently with gemcitabine).
The most common adverse reactions in pivotal study PA.3 in pancreatic cancer patients receiving erlotinib 100 mg plus gemcitabine were fatigue, rash and diarrhea. In the erlotinib plus gemcitabine arm, Grade 3/4 rash and diarrhea were each reported in 5% of patients. The median time to onset of rash and diarrhea was 10 days and 15 days, respectively. Rash and diarrhea each resulted in dose reductions in 2% of patients, and resulted in study discontinuation in up to 1% of patients receiving erlotinib plus gemcitabine. (See Tables 1 and 2.)

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