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M.S. Yaksic
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P3.03 - Chemotherapy/Targeted Therapy (ID 719)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.03-019 - Activity of PARP Inhibitor in NSCLC with Germline and Somatic Mutation and in Silico Chemotherapy Lethality (ID 9740)
09:30 - 09:30 | Author(s): M.S. Yaksic
- Abstract
Background:
Challenges in Precision and Personalized Medicine with interpatient variation needs individualized protocols. PARP Inhibition may be one modality of treatment of NSCLC, as coadjutant to chemotherapy.
Method:
A 66 years old male has been diagnosed with lung adenocarcinoma since 02-06-2016, c T4 c N1 c M1a (pleura and pericardium), had been exposed to carboplatin and pemetrexed for 6 cycles (January to March 2016) with disease progression, and peripheral neuropathy. He didn’t have EGFR mutation, ALK translocation, MET/RET or ROS-1 FISH alterations. He had been treated with radiation therapy from September to November 2016 with 60 Gy, IMRT, and after he received Nivolumab, from November 2016 to Abril 2017 with radiological progression. He had been tested by RCGG in May 2017 looking for circulating tumor cells in vitro (the culture contains all substances measured to apoptotic ability using oncogene apoptosis kit; the result is confirmed by cultures of the tumor or circulating tumor cells), Idengen (inherited hot-spot mutations), and Guardiant 360 by liquid biopsy (circulating DNA sequencing somatic mutations).
Result:
With the Idengene test, he has had PALB2 inherited mutation germline with possible pathogenic significance, BRCA1 and BRCA2 with unknown pathogenic significance. Also, he had NBN, PTCH2, and PTEN as possible pathogenic significance. With the Guardiant 360 test, he had BRCA1, C24Y, NF1, R416Q somatic mutations. With the RGCC test, the specific tumor appears to have resisting populations because of the MDR1 overexpression that can be reversed using inhibitors of ABCG2 pumps. Also, the neoplastic cells have the greatest sensitivity in the alkylating agent (cisplatin, mitomycin), in the tubulin dimmer polymerization inhibitors (Vinorelbine). Inhibitor of Akt/mTOR pathway can be used, as Everolimus, temsirolimus. He has partial sensibility to nucleus spindle stabilizer I (paclitaxel, docetaxel), II (vincristine, vinblastine), and nucleoside analogues (methotrexate, gemcitabine, pemetrexed). Therefore he has been exposed to oral Olaparib 300 mg BID, intravenous Gemcitabine 600 mg/m2, and oral vinorelbine 60mg/m2 weekly both., with good tolerability, and improvement of Performance Status.
Conclusion:
PARP Inhibitor can be a target therapy in personalized medicine, guided by PALB2 / BRCA 1 / 2 mutations in codons inherited and / or somatic mutations, in addition to gemcitabine and vinorelbine in lung adenocarcinoma resistant to platinum/pemetrexed. The addition of Olaparib was possible in this patient, and feasible with a good tolerability, maybe impacting the outcome. More studies related to PARP inhibitor and NSCLC need to be developed.
