Physician:

drlo

Dorothy Lo, MD, MHA, FRCPC
Medical Oncologist
Division of Hematology/Oncology,
St. Joseph’s Health Centre
Toronto, Ontario

Presentation:

  • 55-year-old Asian male.
  • Smoking history of 30 pack-years.
  • Presented with history of intermittent cough with occasional blood-tinged sputum (4 months), dyspnea (2 months), frontal headache (3 weeks), leg edema with concomitant cellulitis, and anasarca (few days).
  • Also noted were impaired mobility (in part secondary to anasarca) and thrush.
  • Absence of chest or bone pain.
  • ECOG PS of 2.

Laboratory and Clinical Findings:

ctscan_baseline
CT scan at baseline

  • Head CT scan and MRI revealed 10 bilateral brain lesions, vasogenic cerebral edema, and mass effect.
  • Chest CT revealed a 5-cm lesion in the left upper lobe of the lung, along with left upper lobe atelectasis, left pleural effusion, mediastinal adenopathy, and multiple small bilateral lung nodules.
  • Bronchoscopy showed abnormal mucosa in the left upper lobe bronchus and carina.
  • Abdominal CT showed mild ascites but no liver or adrenal lesions; there was also no evidence of liver dysfunction or clinical CHF.
  • Bone scan revealed multiple bone metastases, including in the right femur, left acetabulum, and posterolateral 7th rib; Doppler ultrasound of legs showed no venous thromboembolism.
  • Cytology from thoracentesis revealed adenocarcinoma.
  • Immunohistochemistry from a lung biopsy of the left upper lobe lesion showed positive staining for CK7 and TTF-1, consistent with lung adenocarcinoma.
  • Mutational analysis revealed an activating EGFR mutation (Del19) and no ALK mutations.

Diagnosis:

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

Treatment:

The patient was:

  • Started on dexamethasone, which was tapered post-radiation;
  • Referred to a radiation oncologist and received whole-brain radiation (20 Gy in 5 fractions);
  • Referred to a thoracic surgeon for thoracentesis, chest tube insertion, and pleurodesis;
  • Treated with nystatin for thrush, intravenous cefazolin (stepped down to oral cephalexin) for leg cellulitis, and denosumab to manage SREs from bone metastases;
  • Prescribed afatinib 40 mg/day (PO); and
  • Counselled on the appropriate preventative care for and management of potential afatinib-related AEs, including diarrhea, skin rash, paronychia, and stomatitis.

Outcome:

ctscan2_after treatment
CT scan at 2 months

  • After starting treatment with afatinib, the patient exhibited:
    • Minor decreases in the sizes of the predominant left upper lobe lung mass and other pulmonary lesions;
    • Improved mobility;
    • Increased appetite and weight gain; and
    • Resolution of the anasarca.
  • The patient was treated with afatinib until progression at 9 months.
  • Other interventions produced improvements in respiratory symptoms and resolution of the headache and leg edema with cellulitis.

Adverse Event Management:

Afatinib was generally well tolerated. Over the course of treatment, the patient exhibited:

  • Diarrhea (grade 1): Managed with intermittent loperamide.
  • Stomatitis (grade 1): Managed with intermittent magic mouthwash (diphenhydramine liquid, nystatin liquid, dexamethasone, sterile water) and lidocaine topical gel.
  • Paronychia (grade 1): Managed with counselling on good local hand and nail care.

Conclusion:

  • This patient with EGFR M+ adenocarcinoma of the left lung had a rapid and durable partial response to first-line treatment with afatinib.
  • Clinical status, ECOG PS, and symptoms all improved during 9 months of treatment with afatinib.
  • Afatinib was generally well tolerated; AEs were as predicted, mild (grade 1), and manageable.

* Based on physician’s experience with an actual patient.
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):3327–34.

Abbreviations: AE = adverse event; ALK = anaplastic lymphoma kinase; CHF = congestive heart failure; CK7 = cytokeratin 7; CT = computed tomography; Del19 = exon 19 deletions; ECOG PS = Eastern Cooperative Oncology Group performance status; EGFR = epidermal growth factor receptor; M+ = mutation-positive; MRI = magnetic resonance imaging; PO = per os (by mouth); PRO = patient-reported outcomes; SRE = skeletal-related event; TTF-1 = thyroid transcription factor 1