The following information helps you to find FDA Alerts and Pharmacist’s Applications to Practice quickly and easily. In cooperation with the Food and Drug Administration (FDA), and as a service to our members, HOPA periodically distributes information about newly approved therapies for cancer patients from FDA’s Office of Oncology Drug Products Director, Dr. Richard Pazdur to inform oncologists and professionals in oncology-related fields in a timely manner. Links to product labels will take you to relevant clinical information on the indication, contraindications, dosing, and safety. In sending this information, HOPA does not endorse any product or therapy and does not take any position on the safety or efficacy of the product or therapy described.

Along with HOPA’s Publications Committee, members also review new drug updates and provide analysis and research on the application of these new drugs or indications. Pharmacist’s Applications to Practice, or PAP, are listed after drugs that include the additional analysis.

You can also find additional information on FDA Alerts and Updates by listening to FDA Drug Safety Podcasts.

January 12, 2018

On January 12, 2018, the Food and Drug Administration granted approval to afatinib (Gilotrif®, Boehringer Ingelheim Pharmaceutical, Inc.) for a broadened indication in first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have non-resistant epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test.

Approval was based on demonstration of durable responses in a subset of 32 afatinib-treated patients with metastatic NSCLC harboring non-resistant EGFR mutations (S768I, L861Q, and/or G719X) other than exon 19 deletions or exon 21 L858R substitutions enrolled in one of three clinical trials (LUX-Lung 2 [NCT00525148], LUX-Lung 3 [NCT00949650], and LUX-Lung 6 [NCT01121393]).

Non-resistant EGFR mutations were identified using either Sanger sequencing or by the therascreen® EGFR RGQ PCR Kit. EGFR mutations included in the non-resistant subgroup demonstrated inhibition of cellular proliferation in EGFR-mutant dependent cell lines at clinically relevant concentrations of afatinib. All patients in the subgroup received afatinib 40 mg or 50 mg orally once daily.

The confirmed overall response rate, as assessed by independent radiology review, was 66% (95% confidence interval 47, 81). Among the 21 responders, the proportion of patients with response duration of ≥12 months was 52% and the proportion with response durations of ≥18 months was 33%.

The most common adverse reactions reported for afatinib (≥20%) across clinical trials are diarrhea, rash/acneiform dermatitis, stomatitis, paronychia, dry skin, decreased appetite, nausea, vomiting, and pruritus.

The recommended dose of afatinib is 40 mg orally, once daily.

Full prescribing information is available at:

FDA initially approved afatinib in 2013 for the treatment of patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test and in 2016 for metastatic, squamous NSCLC progressing after platinum-based chemotherapy.

FDA granted priority review and orphan drug designation to afatinib. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at:

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).


Pharmacist's Applications to Practice

Afatinib for Previously Untreated Non-Small-Cell Lung Cancer

Author: Allison Baxley, PharmD BCOP
Stephenson Cancer Center
Oklahoma City, Oklahoma

What is the potential role for afatinib in the treatment of non-small-cell lung cancer (NSCLC)?

  • Afatinib was previously approved, alongside erlotinib and gefitinib, as a first-line treatment option for patients with one of two sensitizing epidermal growth factor receptor (EGFR) mutations: exon 19 deletions or exon 21 L858R mutation.1,2
  • Exon 19 deletions and exon 21 L858R mutations account for approximately 90% of all mutation-positive NSCLC, although several additional mutations have been identified.3
  • The recent change to the approved indications for afatinib broadens its use to be the first agent to target three additional sensitizing EGFR mutations: L861Q, G719X, and S768I.1,3
    • Data supporting this expanded indication come from subgroup analyses of patients with EGFR mutations from previously reported clinical trials: LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Of the numerous uncommon mutations evaluated in this analysis, afatinib was found to be active (i.e., it demonstrated objective responses) in three particular mutations: L861Q, G719X, and S768I.3
  • Afatinib is also indicated for the treatment of patients with metastatic squamous cell NSCLC whose disease has progressed on platinum-based chemotherapy.1,2

What role can the pharmacist play in the management of patients on afatinib?

  • For consideration in front-line treatment, patients must exhibit one of five sensitizing EGFR mutations:
    • exon 19 deletion
    • exon 21 L858R mutation
    • L861Q mutation
    • G719X mutation
    • S768I mutation.
  • The dose of afatinib is 40 mg once daily. Afatinib should be administered on an empty stomach either 1 hour before or 2 hours after a meal. Absorption is decreased with high-fat meals.
    • Afatinib is available in 20-mg, 30-mg, and 40-mg tablets.
    • Treatment should be given until the disease progresses or an unacceptable level of toxicity is reached.
  • Afatinib has low emetic potential and therefore does not require concomitant administration of prophylactic anti-emetics.
  • Patients should be monitored for potential drug interactions. Afatinib is a substrate of P-glycoprotein and may require dose adjustments.
    • For patients on P-glycoprotein inhibitors: if concomitant therapy is not tolerated, reduce afatinib by 10 mg.
    • For patients on P-glycoprotein inducers: increase afatinib dose by 10 mg as tolerated.
  • Women of reproductive potential should use highly effective contraception during therapy and for at least 2 weeks after the last dose.
  • Consider obtaining left ventricular ejection fraction (LVEF) prior to starting therapy in patients with cardiac risk factors, and monitor periodically.4
  • Afatinib may cause significant dermatologic toxicity, including acneiform rash (all grades reported in 70%–90% of patients, grade 3 reported in 7%–16%). Several treatment guidelines exist to guide providers in the management of EGFR-induced rash, including topical and systemic therapies for prevention and treatment.
  • Grade 3 and 4 diarrhea (10%–15% and 0.8%, respectively) was reported in clinical trials, typically within the first 6 weeks of therapy. Patients with diarrhea may need systemic therapy with antidiarrheals or dose reduction or interruption.
  • Hepatotoxicity has been reported; therefore liver-function tests should be monitored at baseline and periodically. Liver-test abnormalities occurred in 6%–17.5% of patients, with 0.2%–3.5% being grade 3/4).
  • Ocular toxicity (including severe keratitis in 2.2% of patients) has been reported. Patients must be counseled to report blurred vision, eye pain, light sensitivity, and other visual changes.
  • Boehringer Ingelheim offers several patient assistance options for those taking afatinib: co-pay assistance, alternative funding support, and a bridge program.

 Clinical Pearls

  • All patients with advanced-stage lung adenocarcinoma or tumors with an adenocarcinoma component should be tested for EGFR mutations.5
    • FoundationOne and the therascreen EGFR RGQ PCR Kit are approved by the FDA as companion diagnostic devices for afatinib.
  • The National Comprehensive Cancer Network (NCCN) ranks afatinib as slightly less safe than gefitinib or erlotinib, so careful consideration of these agents must be made when a patient exhibits exon 19 deletions or exon 21 L858R mutations. In those with L861Q, G719X, or S768I mutations, afatinib is currently the only indicated treatment option.
    • NCCN has begun providing evidence blocks to rank various qualities of treatment choices. One such component is “Safety of Regimen/Agent.” Afatinib has received a ranking of 3, or “mildly toxic,” to indicate that it may interfere with a patient’s ability to carry out activities of daily living (ADLs). Both gefitinib and erlotinib have been given a ranking of 4, or “occasionally toxic,” to indicate that they cause little interference with ability to perform ADLs.
    • Afatinib and erlotinib have similar rates of dermatologic and gastrointestinal toxicities. Although they have not been compared head-to-head, in individual clinical trials, a higher percentage of patients receiving afatinib were reported to have hematologic toxicities and hepatotoxicity than patients receiving erlotinib. Patients receiving gefitinib in clinical trials reported lower rates of diarrhea and dermatologic toxicity than those reported with either erlotinib or afatinib.
    • At this time (March 2018) no data have shown a significant difference in overall survival rates between erlotinib, gefitinib, and afatinib in patients with exon 19 deletions or exon 21 L858R mutations.2


  1. Gilotrif (afatinib) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceutical, Inc.; January 2018.
  2. National Comprehensive Cancer Network Guidelines. Non-Small Cell Lung Cancer. Version 3.2018. Accessed February 27, 2018.
  3. Yang J, Sequist LV, Geater SL, et al. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-lung 2, LUX-lung 3, and LUX-lung 6. Lancet Oncol. 2015;16:830-838
  4. Afatinib monograph. (Lexi-Drugs). Lexi-Comp, Inc. Accessed February 27, 2018.
  5. Leighl NB, Rekhtman N, Biermann WA, et al. Molecular testing for selection of patients with lung cancer for epidermal growth factor receptor and anaplastic lymphoma kinase tyrosine kinase inhibitors. J Clin Oncol. 2014;32:3673-3679.