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Osamu Takakuwa



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    EP1.01 - Advanced NSCLC (ID 150)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.01-12 - SNPs of Organic Cation Transporter 6 Associate with the Efficacy of Platinum Combination Chemotherapy (Now Available) (ID 170)

      08:00 - 18:00  |  Author(s): Osamu Takakuwa

      • Abstract
      • Slides

      Background

      Platinum derivatives (cisplatin or carboplatin) are key antitumor drugs to non-small cell lung cancer in combination therapy with not only other cytotoxic agents or vascular endothelial growth factor but also kinase inhibitors or immune checkpoint inhibitors. However, the predictive biomarker of effectiveness about platinum-based chemotherapy is still unclear.

      Organic cation transporter 6 (OCT6) is one of the solute carrier transporters (coded by SLC22A16) which transport substrates by facilitated diffusion or secondary active transport. We previously reported that OCT6 was involved in platinum drug resistance by mediating platinum drug influx in cancer cell. Single nucleotide polymorphisms (SNPs) in genome sequences bring about changes in the amino acid sequence, alter the protein structure, and result in individual differences.

      The aim of this study is to solve the association between the efficacy of cytotoxic chemotherapy including platinum derivatives and SNPs.

      Method

      We retrospectively screened 78 advanced non-squamous non-small cell lung cancer patients who received platinum derivatives (cisplatin or carboplatin) and pemetrexed combination therapy for the first line chemotherapy between October/2010 and May/2018. We investigated the association between SNPs (rs714368, rs723685, and rs12210538) of SLC22A16 or patients’ characteristics and clinical outcomes.

      Result

      The median age of patients was 67 years old. Sixty patients were male and 61 patients were current or former smokers. The historical features of Sixty-eight patients were adenocarcinoma, and 18 patients had positivity of EGFR mutation or ALK fusion. We excluded rs12210538 from covariable of this study as all patients had major homo allele about rs12210538.

      The clinical outcomes of this study were similar to those of previous clinical studies.

      We found the patients with phenotype “A” of rs714368 had higher disease control rate (DCR) and longer duration of progression free survival (PFS) compared to phenotype “G” [response rate (RR), 31.4 % vs 25%, p >0.99; DCR, 85.7% vs 37.5%, p<0.01; median PFS, 154 days vs 26,5 days, p<0.01; median overall survival (OS), 666 days vs 471 days, p=0.69, respectively]. On the other hand, genotype of rs723685 had no association with treatment outcomes [genotype “TT” vs “TC”, RR, 32.8% vs 18.2%, p=0.49; DCR, 83.6% vs 63.6%, p=0.21; PFS, 132 days vs 111 days, p=0.37; OS, 558 days vs 1014 days, p=0.46]. Phenotype A of rs714368 and earlier stage were good predictive factor about PFS in Cox proportional hazard model.

      Conclusion

      Gene polymorphisms of rs714368 may change the function of OCT6 and influence the efficacy of platinum combination chemotherapy.

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