Dorothy Lo, MD, MHA, FRCPC
Division of Hematology/Oncology,
St. Joseph’s Health Centre
- 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:
- 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.
- Based on imaging, lung biopsy, and molecular testing findings, this patient was diagnosed with EGFR M+ (Del19) stage IV adenocarcinoma of the lung.
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.
- 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.
- 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