• Jeffrey Rothenstein, MD
  • RS McLaughlin Durham Regional Cancer Centre Lakeridge Health, Oshawa, Ontario
  • Scarborough General Hospital Oncology Clinic, Scarborough, Ontario


  • A 65-year-old Asian female
  • History of GERD, osteoarthritis, appendectomy, and tonsillectomy
  • Remote light smoker (i.e., “social”); however, quit at the age of 38 years
  • Presented to the emergency department with left-sided arm and leg weakness
  • Initial clinical impression is stroke
  • Slight pain in the chest, as well as in the arm and shoulder, was noted
  • Additional symptoms of cough and dyspnea were noted

Laboratory and Clinical Findings:

  • Head CT (non-contrast) was unremarkable
  • Brain MRI revealed a solitary, right-sided, 1.4-cm enhancing lesion consistent with metastasis
  • Concern for possible lesion in C4 vertebral body
  • Further workup recommended
  • Bone scan showed diffuse abnormalities consistent with metastatic disease, including abnormal activity in skull, ribs, spine, iliac wing, and left femur
  • Chest CT revealed a 2.7-cm left upper lobe mass, diffuse small pulmonary nodules and a small left pleural effusion
  • Unremarkable mammogram and breast ultrasound
  • Lung biopsy revealed acinar growth pattern and positive staining for TTF1 consistent with adenocarcinoma
  • Mutational analysis demonstrated an activating EGFR mutation (Del19)


  • Based on imaging, lung biopsy, and molecular testing findings, this patient was diagnosed with stage 4 adenocarcinoma of the lung with EGFR M+ (Del19)


  • Stereotactic radiation was delivered to the brain lesion
  • During the course of this treatment, the patient developed pain from bone metastases
  • Patient was referred to palliative care for pain management and received palliative radiation to ribs, iliac, and left femur metastases
  • Subsequently, patient was seen at a medical oncology clinic, where she was initiated on denosumab to manage SREs from bone metastases
  • The patient was administered GIOTRIF® (afatinib; 40 mg PO OD)
  • Counselled patient on preventative measures for skin care, including moisturizers and sunscreen
  • Gave patient up-front information on AEs and prescriptions to use in case of AEs, including Imodium® (Ioperamide) for diarrhea, Westcort® (hydrocortisone valerate) for skin rash, and minocycline in case of more significant rash
  • Gave patient up-front instructions to call clinic if any issues with diarrhea, rash, paronychia, and stomatitis occur, and to suspend the drug and seek medical attention if AEs become severe


  • Subsequent to starting GIOTRIF, no further deterioration of cough, dyspnea, and chest pain was noted
  • CT scan revealed a partial response in the LUL primary tumour
  • Patient continues taking GIOTRIF with no need for dose adjustments

AE Management:

Over the course of treatment:

  • Skin rash (grade 1): Managed with Westcort (hydrocortisone valerate). Generally well controlled.
  • Stomatitis (grade 1): Managed with Tantum Verde® (benzydamine oral rinse). Generally well controlled.
  • Diarrhea (grade 1): Managed with dietician consult and Imodium (loperamide). Generally well controlled.
  • Paronychia and cracking at fingertips (grade 2): Managed with local care and Betaderm® (betamethasone valerate). Ongoing symptoms and management.


  • This patient with EGFR M+ adenocarcinoma of the lung responded well to GIOTRIF
  • GIOTRIF was generally well tolerated and showed a manageable AE profile in this patient

* Hypothetical case study based on the physician’s experience.
† In LUX-Lung 3, the largest (N = 345), multinational, randomized, open-label, phase III registration trial, the efficacy and safety of GIOTRIF (afatinib; 40 mg PO OD until tumour progression) vs. pemetrexed/cisplatin (500 mg/m2 / 75 mg/m2 IV d1, q3w up to 6 cycles) was evaluated in the first-line setting in patients with EGFR M+ metastatic lung adenocarcinoma. The primary endpoint was PFS and secondary endpoints included PRO and tumour response. GIOTRIF demonstrated a significant improvement in disease-related symptoms and tumour response vs. pemetrexed/cisplatin:

  • Delayed the time to deterioration of cough (median not reached vs. 8.0 months; HR 0.60; P = 0.007) and dyspnea (10.3 vs. 2.9 months; HR 0.68; P = 0.01)
  • Althought time to deterioration of pain was not statistically significant (4.2 vs. 3.1 months; HR 0.83; P = 0.19), time to deterioration of chest pain was significantly delayed (HR 0.65; P = 0.023)
  • ORR was significantly higher (56.1% vs. 22.6%; OR 4.66; P<0.0001)

Abbreviations: AE = adverse event; CT = computerized tomography; d1 = Day 1; Del19 = exon 19 deletions; EGFR = epidermal growth factor receptor; GERD = gastroesophageal reflux disease; HR = hazard ratio; IV = intravenous; LUL = left upper lobe; M+ = mutation-positive; MRI = magnetic resonance imaging; OD = once daily; OR = odds ratio; ORR = objective response rate; PO = per os (by mouth); PRO = patient-related outcomes; q3w = every 3 weeks;SRE = skeletal-related event; TTF1 = thyroid transcription factor-1