Safety

Body: 

Established safety profile based on >4200 patients in clinical trials1

ARs REPORTED IN LUX-Lung 3 IN ≥10% OF GILOTRIF-TREATED PATIENTS1

Safety chart

 

Other clinically important ARs observed in patients treated with GILOTRIF include decreased appetite (29%), nausea (25%), and vomiting (23%)1

AR=adverse reaction.
*None of the ARs in this table except stomatitis (1 patient on GILOTRIF [0.4%]) were grade 4 in severity.
†Includes stomatitis, aphthous stomatitis, mucosal inflammation, mouth ulceration, oral mucosa erosion, mucosal erosion, mucosal ulceration.
‡Includes acne, acne pustular, dermatitis, acneiform dermatitis, dermatosis, drug eruption, erythema, exfoliative rash, folliculitis, rash, rash erythematous, rash follicular, rash generalized, rash macular, rash maculo-papular, rash pruritic, rash pustular, skin disorder, skin erosion, skin exfoliation, skin fissures, skin lesion, skin reaction, skin toxicity, skin ulcer.
§Includes paronychia, nail infection, nail bed infection.

 

Serious ARs and Discontinuations1

SERIOUS ARs REPORTED IN LUX-Lung 31

  • Serious ARs were reported in 29% of patients treated with GILOTRIF. The most frequent serious ARs reported in patients treated with GILOTRIF were diarrhea (6.6%), vomiting (4.8%), and dyspnea, fatigue, and hypokalemia (1.7% each). Fatal ARs in GILOTRIF-treated patients included pulmonary toxicity/ILD-like ARs (1.3%), sepsis (0.43%), and pneumonia (0.43%)

DISCONTINUATIONS IN LUX-Lung 3

  • Discontinuation of therapy in GILOTRIF-treated patients for ARs was 14%1
  • The most frequent ARs that led to discontinuation in GILOTRIF-treated patients were diarrhea (1.3%), ILD (0.9%), and paronychia (0.9%)1

 

 

 

In Advanced SqCC of the Lung: ARs Reported in LUX-Lung 8 in ≥10% of GILOTRIF treated patients1

Safety chart

SqCC=squamous cell carcinoma
†Includes stomatitis, aphthous stomatitis, mucosal inflammation, mouth ulceration, oral mucosa erosion, mucosal erosion, mucosal ulceration.
‡Includes acne, dermatitis, acneiform dermatitis, eczema, erythema, exfoliative rash, folliculitis, rash, rash generalized, rash macular, rash maculo-papular, rash pruritic, rash pustular, skin exfoliation, skin fissures, skin lesion, skin reaction, skin toxicity, skin ulcer.
§Includes paronychia, nail infection, nail bed infection.

 

Serious AR Reported in LUX-Lung 81

  • Serious ARs occurred in 44% of patients treated with GILOTRIF. The most frequent serious ARs in patients treated with GILOTRIF were pneumonia (6.6%), diarrhea (4.6%), and dehydration and dyspnea (3.1% each). Fatal ARs in GILOTRIF-treated patients included ILD (0.5%), pneumonia (0.3%), respiratory failure (0.3%), acute renal failure (0.3%), and general physical health deterioration (0.3%).

 

Discontinuation in LUX-Lung 8

  • Treatment-related discontinuation due to any ARs was similar in both arms (20% vs 17% for GILOTRIF vs erlotinib)13
  • The most frequent ARs that led to discontinuation in GILOTRIF-treated patients were diarrhea (4.1%) and rash/acne (2.6%)1

References: 1. GILOTRIF [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc. 2. Hochmair MJ, Morabito A, Hao D, et al. Sequential treatment with afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer: an observational study [published online October 19, 2018]. Future Oncol. doi:10.2217/fon-2018-0711 3. Halmos B, Tan EH, Soo Ra, et al. Impact of afatinib dose modification on safety and effectiveness in patients with EGFR mutation-positive advanced NSCLC: results from a global real-world study (RealGido). Lung Cancer. 2019;127:103-11. 4. Yang JCH, Wu YL, Schuler M, et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015;16(2):141-151. 5. Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013;31(27):3327-3334. 6. Ke EE, Zhou Q, Zhang QY, et al. A higher proportion of the EGFR T790M mutation may contribute to the better survival of patients with exon 19 deletions compared with those with L858R. J Thorac Oncol. 2017;12(9):1368-1375. 7. Data on file. Boehringer Ingelheim. CTR. 8. Lee CK, Wu YL, Ding PN, et al. Impact of specific epidermal growth factor receptor (EGFR) mutations and clinical characteristics on outcomes after treatment with EGFR tyrosine kinase inhibitors versus chemotherapy in EGFR-mutant lung cancer: a meta-analysis. J Clin Oncol. 2015;33(17):1958-1965. 9. Yang JC, 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(7):830-838. 10. Yang JCH, Wu JYS, Hsia TC, et al. Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial. Lancet Oncol. 2012;13:539-548. 11. Wu YL, Zhou C, Hu CP, et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014;15(2):213-222. 12. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: non-small cell lung cancer, version 5. 2018. 13. Soria JC, Felip E, Cobo M, et al. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2015;16(8):897 907. 14. Yang JCH, Sequist LV, Zhou C, et al. Effect of dose adjustment on the safety and efficacy of afatinib for EGFR mutation-positive lung adenocarcinoma: post hoc analyses of the randomized LUX-Lung 3 and 6 trials. Ann Oncol. 2016;27(11):2103-2110.  15. U.S. Food & Drug Administration (FDA). FDA broadens afatinib indication to previously untreated, metastatic NSCLC with other non-resistant EGFR mutations (press release). https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm592558.htm. Accessed 3.13.2019.

Indications and usage

  • GILOTRIF (afatinib) tablets is indicated for the 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.

    Limitation of Use: Safety and efficacy of GILOTRIF have not been established in patients whose tumors have resistant EGFR mutations.

  • GILOTRIF is indicated for the treatment of patients with metastatic squamous NSCLC progressing after platinum-based chemotherapy.