Robert El-Maraghi, MD, FRCPC
Simcoe Muskoka Regional Cancer Centre and the
Royal Victoria Regional Health Centre
- 61-year-old Caucasian male.
- Presented to the emergency room with 4-month history of progressive mid-back and left pelvic pain, mild cough, and occasional scant hemoptysis.
- Patient had an ECOG PS of 1.
Laboratory & Clinical Findings:
- Chest CT scan showed a 2.4-cm lesion in the right lower lobe of the lung that was associated with right hilar and mediastinal lymphadenopathy, innumerable small bilateral lung nodules, bilateral pleural effusions, and a small pericardial effusion.
- Lumbar X-ray revealed a compression fracture of the T12 vertebra.
- Bone scan and spine MRI confirmed diffuse metastatic bone disease, including a pathological fracture of the T12 vertebra.
- Abdominal and pelvic CT scan demonstrated a 3-cm left-sided pelvic mass and a 2.4‑cm nodule in the left adrenal gland.
- Bronchoscopy showed abnormal submucosal infiltrative disease; biopsies were positive for adenocarcinoma.
- Thoracentesis confirmed presence of adenocarcinoma.
- Mutational analysis revealed an activating EGFR mutation (L858R).
- Based on imaging, lung biopsy, and molecular testing findings, this patient was diagnosed with EGFR M+ (L858R) stage IV adenocarcinoma of the lung.
The patient was:
- Referred to palliative care for pain management.
- Given palliative radiation to the T12 vertebra, sacrum, and pelvis.
- Initiated on denosumab to manage SREs from bone metastases.
- Administered afatinib (40 mg PO OD).
- Counselled on appropriate skin care and diarrhea management.
- The patient displayed partial responses to afatinib in the EGFR M+ lesion of the right lung and to radiation therapy in the affected areas of bone.
- A CT scan at 9 months revealed a lesion in the left lung, which suggested oligoprogression.
- The patient felt clinically well and, therefore, remained on afatinib treatment; SBRT was administered to the left lung lesion, which responded partially.
- The patient discontinued afatinib treatment at 17 months, upon the progression of additional lesions. Most of the bilateral pulmonary nodules were slightly larger, including a nodule in the pleura and one at the cardiophrenic angle; the pleural effusions were also larger. There were also numerous additional mediastinal lymph nodes, enlargement of the left para-aortic lymph node, and a new liver metastasis. The bone metastases were stable.
Adverse Event Management:
Afatinib was generally well tolerated. Over the course of treatment, the patient experienced:
- Skin rash (grade 1): Managed with topical steroid cream (hydrocortisone 1% with clindamycin 2%).
- Diarrhea (grade 1): Managed with loperamide.
- This patient with EGFR M+ adenocarcinoma of the lung had a durable response to therapy.
- The patient, who took afatinib for a total of 17 months (including 8 months in the setting of oligoprogression), achieved clinical benefit for the treatment of an EGFR M+ lesion in the right lung.
- Afatinib was generally well tolerated; AEs were as predicted and manageable.
* Based on physician’s experience with an actual patient.
† The efficacy and safety of afatinib (40 mg PO OD until tumour progression) vs. pemetrexed/cisplatin (500 mg/m2 / 75 mg/m2 iv d1, q3w up to 6 cycles) in the first-line setting was evaluated in LUX-Lung 3, the largest (N = 345) multinational, randomized, open-label, phase III registration trial of patients with EGFR M+ metastatic lung adenocarcinoma to date.1 The primary endpoint was PFS, and secondary endpoints included tumour response. Afatinib demonstrated a significant PFS benefit and a significant improvement in tumour response vs. pemetrexed/cisplatin (PFS: 11.1 months vs. 6.9 months [HR 0.58; p = 0.0004]; ORR [CR + PR]: 56.1% vs. 22.6% [OR 4.66; p <0.0001]; CR was achieved in one patient in the afatinib arm and in no patients in the pemetrexed/cisplatin arm).
Abbreviations: AE = adverse event; CR = complete response; CT = computerized tomography; d1 = day 1; ECOG PS = Eastern Cooperative Oncology Group performance status; EGFR = epidermal growth factor receptor; HR = hazard ratio; IV = intravenous; L858R = exon 21 L858R point mutation; M+ = mutation-positive; MRI = magnetic resonance imaging; OD = once daily; OR = odds ratio; ORR = objective response rate; PFS = progression-free survival; PO = per os (by mouth); PR = partial response; q3w = every 3 weeks; SBRT = stereotactic body radiation therapy; SRE = skeletal-related event; T12 = twelfth thoracic
Reference: 1. 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.