EGFR+ NSCLC: Recent Data From FLAURA2
Joshua K. Sabari, MD, reviews clinical trial data from FLAURA2 on osimertinib plus chemotherapy in patients with EGFR-mutated advanced lung cancer.
Case: A 73-Year-Old Man with EGFR+ NSCLC
Clinical Presentation:
- 73-year-old man initially presents with complaints of a persistent nonproductive cough, dyspnea on mild exertion, and an unintentional 10 lb. weight loss over prior 3 months
Past Medical History:
- Coronary Artery Disease: treated with rosuvastatin 20 mg QD.
- Hypertension, controlled on ARB QD.
- Hyperlipidemia, treated with atorvastatin 20 mg QD.
- COPD, maintained on triple inhalation therapy BID.
Social History:
- Retired high school teacher; married with 2 adult children.
- 50 pack-year smoking history: quit tobacco habit 5 years previously
Initial Clinical Workup and Diagnosis:
Physical Examination
- Ambulatory but no longer drives and is capable of self-care without assistance.
- Height: 5’10”; Weight:78 kg (172 lbs.)
- ECOG PS: 1
- Diminished breath sounds auscultated over right upper lobe.
Pulmonary Function Tests
- FEV1 2.1 L (68% predicted) indicative of moderate obstruction.
Imaging Studies:
- Chest CT: showed a 4.2 x 3.1 cm spiculated mass in the right upper lobe with suspected hilar lymph node involvement.
- PET Scan: confirms hypermetabolic right hilar and subcarinal lymph nodes activity suggestive of malignancy.
- MRI of Abdomen and Brain and Tech99 Bone Scintigraphy: no evidence of metastases.
Diagnostic Procedure:
- Bronchoscopy with Biopsy: gross appearance of specimen obtained from right upper lobe consistent with adenocarcinoma of the lung.
- Histopathology: confirms lung adenocarcinoma (Grade 2; pT2b pN1 [2/17 lymph nodes positive]; V0 R0), with partially papillary and partially tubular morphology.
Neoadjuvant Therapy and Surgical Resection:
- Patient receives 4 cycles of cisplatin + pembrolizumab + pemetrexed.
- He tolerated the regimen well with manageable episodes of fatigue, nausea, and sporadic neuropathy of the bilateral upper extremities.
- Post-Treatment Restaging PET Scan: showed a good partial response.
- Surgical Resection:
- Lobectomy of the RUL with hilar and mediastinal lymphadenectomy via video-assisted thoracoscopic surgery (VATS).
Surgical Pathology Report:
- ypT2aN1 (3/16 lymph nodes positive) with negative margins; Stage IIa
- Adjuvant RT was recommended, but the patient declined.
Six Months Later:
- Patient returns to his oncologist with complaints of recurrent, mid-to-low back pain.
- Post-Operative Chest CT: displays scattered pulmonary nodules suspicious for metastatic disease progression.
- Thoraco-lumbar MRI: negative for bony metastases.
Second Line Systemic Therapy:
- Amivantamab was initiated with a weekly, weight-based infusion x4w(split dose, Days 1-2, Week 1), and thereafter q2w.
- The patient developed a minor infusion reaction on day 1 of therapy, which resolved with application of cool compresses to the site and acetaminophen, 500 mg PO q4h, prn.
Repeat Imaging at 8 Weeks:
- The patient experienced a good partial response.
- He will continue to be followed regularly by his oncologist.
This is a video synopsis/summary of a Case-Based Peer Perspectives featuring Joshua K. Sabari, MD.
This video features a discussion on 2 emerging frontline treatment options for EGFR-mutant metastatic non–small cell lung cancer (NSCLC): the FLAURA2 trial of osimertinib plus chemotherapy vs osimertinib monotherapy.
The FLAURA2 trial showed improved progression-free survival with osimertinib plus pemetrexed chemotherapy compared to osimertinib alone (25-26 months vs 16-17 months) but no difference in overall survival so far. An exploratory analysis suggested less centra nervous system progression with chemotherapy added, though routine brain MRI was not done. Toxicity is higher with chemotherapy, so overall survival data will be important to determine if combination therapy is beneficial upfront vs sequencing chemotherapy after osimertinib progression.
The potential overall survival benefit, if confirmed, would be practice-changing, but the benefit may just reflect progression-free survival prolongation until second-line therapy. Using all options upfront must balance efficacy and toxicity.
These data may help inform optimal sequencing of osimertinib and chemotherapy for eligible patients with EGFR-mutated NSCLC.
Video synopsis is AI-generated and reviewed by Targeted Oncology™ editorial staff.
