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J. Chuang
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-081 - Case Series of HER2 Mutated Metastatic Lung Adenocarcinoma and Response to HER2 Targeted Therapies (ID 799)
09:30 - 09:30 | Author(s): J. Chuang
- Abstract
Background:
HER2 has long been recognized as an oncogenic driver in some breast and gastro-esophageal cancers. More recently, somatic mutations in HER2 have been reported in 1-2% of patients with lung adenocarcinoma, and the promise of HER2 as a treatment target in lung cancer has been suggested using anti-HER2 small molecules and antibodies.
Methods:
Here we report the outcomes of three patients with metastatic lung adenocarcinoma with HER2 mutations being treated with HER2 targeted therapies at a single institution.
Results:
The first patient is a 65yo Caucasian woman, minimal smoking history, with stage IIIA lung adenocarcinoma who then developed recurrent metastatic disease mainly in the liver after completing definitive chemoradiotherapy. She progressed through three lines of chemotherapies, with near replacement of liver with tumor. At that time she was found to have HER2 exon 20 insertion mutation (A775_G776 insSVMA) and was started on vinorelbine and trastuzumab. The main side effect was fatigue, which was tolerable. She achieved radiographic stable disease with 13% reduction of her liver metastasis as her best response by RECIST v1.1 for 6 months and significant clinical improvement before progression of disease in all sites. The second patient is a 60yo Caucasian woman, former smoker, diagnosed with stage IV lung adenocarcinoma with HER2 exon 20 insertion mutation (unknown exact sequence) with extensive bony disease. She was treated with carboplatin, paclitaxel, bevacizumab, and an investigational anti-Met therapy with initial mild decrease in lung mass and nodules after one month, then mild progression for 14 months. She was taken off trial then and started on vinorelbine and trastuzumab, and so far shows no measurable growth after 5 months on therapy. The third patient is a 35yo Asian woman, non-smoker, diagnosed with stage IV lung adenocarcinoma with HER2 exon 20 insertion mutation (unknown exact sequence) with malignant pleural effusions, bilateral lung and brain lesions, and extensive lymph node involvement. She was treated with carboplatin, pemetrexed, and bevacizumab first followed by pemetrexed and bevacizumab maintenance, with initial mild improvement then progression after 4.5 months. She was then treated with erlotinib with rapid progression within 1 month. She was then treated with afatinib 40mg daily based on the HER2 mutation, improved disease after 2 months with best response 21% reduction, then progression after 3 more months (5 months total of clinical benefit). She was then started on vinorelbine and trastuzumab. Treatment was interrupted due to one new brain lesion requiring stereotactic radiation treatment. She has shown partial response with best response of 31% on the latest imaging done 4 months after starting therapy.
Conclusion:
From our single institution experience, HER2 targeted therapy can provide disease control for patients with metastatic HER-2 mutated NSCLC that has progressed on previous therapies. Our results are consistent with the study by Mazières et al. Vinorelbine was dosed as 25 mg/m2 and trastuzumab as 2 mg/kg every 1 week (with 4mg/kg first loading dose) or 6 mg/kg every 3 weeks. All three patients were able to tolerate therapies well with no significant toxicities nor cardiac toxicity.
