- Paul Wheatley-Price, MD
- Division of Medical Oncology, University of Ottawa, Ottawa, Ontario
- The Ottawa Hospital Cancer Centre, General Campus, Ottawa, Ontario
- A 72-year-old Caucasian female
- Patient has a 35-cigarette pack-year smoking history, but quit over 20 years ago
- In late 2012, she presented to her family doctor with tender swelling under the left jaw
- She was initially referred to an ENT surgeon, and a CT scan was ordered
- Patient also presented with some left shoulder pain, but no systemic symptoms, such as anorexia, weight loss, or fatigue
- Patient had an ECOG PS of 1 at baseline
Laboratory and Clinical Findings:
- CT scan revealed a 5.7-cm right upper lobe mass, right hilar lymphadenopathy, and a 2.9-cm left submandibular necrotic-appearing lymph node
- Fine-needle aspiration biopsy of the right upper lobe revealed positive staining for TTF1 and CK7, but not CK20, consistent with adenocarcinoma
- Mutational analysis demonstrated the presence of an activating EGFR mutation (L858R)
- Abdominal and head CT scans did not demonstrate any further visceral metastases; however, an isotope bone scan demonstrated multiple metastases throughout the axial skeleton
Diagnosis and Pathology:
- Based on imaging, lung biopsy, and molecular testing findings, the patient was diagnosed with stage 4 adenocarcinoma of the lung with EGFR M+ (L858R)
- The patient was administered GIOTRIF (afatinib; 40 mg PO OD)
- Patient continues taking GIOTRIF after 13 months with no need for dose adjustments (treatment is still ongoing)
- There has been no need for additional therapies, such as radiotherapy or bone-targeted agents (e.g., bisphosphonates, denosumab, etc.)
- Within a few weeks of commencing treatment, a clinical response was observed:
- After 4 weeks, a CT scan demonstrated that the RUL mass had reduced from 63 × 57 mm to 40 × 32 mm, with a corresponding reduction in the right hilar lymph node
- At 8 weeks, the RUL mass had further reduced to 40 × 18 mm, and further to 31 × 24 mm at 16 weeks
- Thereafter, the disease remained stable, with no evidence of progression on the latest scan after 14 months therapy
- By the first follow-up appointment at 4 weeks, the left submandibular lymphadenopathy was resolved
GIOTRIF® was generally well tolerated. Over the course of treatment:
- Skin rash (grade 1): Managed conservatively without the need for any systemic drugs.
- Diarrhea (grade 1): Managed conservatively with Imodium® (loperamide).
- Paronychia (grade 1): Managed conservatively without the need for any systemic drugs.
- This patient with EGFR M+ adenocarcinoma of the lung had a rapid and durable response to GIOTRIF, and remains on therapy after 14 months
- GIOTRIF has been generally well tolerated, with the AEs being mild and expected
- In line with the LUX-Lung 3 trial data demonstrating the safety and efficacy of GIOTRIF in the EGFR M+ lung adenocarcinoma population, this case demonstrated that GIOTRIF is generally well tolerated and effective
* Based on physician’s experience with an actual patient.
† 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 tumour response vs. pemetrexed/cisplatin (ORR: 56.1% vs. 22.6%; OR 4.66; P<0.0001).
Abbreviations: AE = adverse event; CK7 = cytokeratin 7; CK20 = cytokeratin 20; CT = computerized tomography; d1 = Day 1; ECOG PS = Eastern Cooperative Oncology Group performance status; EGFR = epidermal growth factor receptor; IV = intravenous; L858R = exon 21 L858R point mutation; M+ = mutation-positive; OD = once daily; OR = odds ratio; ORR = objective response rate; PO = per os (by mouth); PRO = patient-reported outcomes; q3w = every 3 weeks; RUL = right upper lobe; TTF1 = thyroid transcription factor-1