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Kazutoshi Komiya
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P1.08 - Locally Advanced NSCLC (ID 694)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.08-006 - Phase I/II Study of Carboplatin, nab-paclitaxel, and Concurrent Radiation Therapy for Patients with Locally Advanced NSCLC. (ID 8356)
09:30 - 09:30 | Author(s): Kazutoshi Komiya
- Abstract
Background:
A regimen of weekly paclitaxel plus carboplatin (CBDCA) with concurrent thoracic radiotherapy is recognized as standard for patients with unresectable stage III lung cancer. Nanoparticle albumin-bound paclitaxel (nab-PTX) is a cremophor-free formulation of paclitaxel to increase solubility and intratumor drug delivery and is effective for patients with advanced NSCLC. The purpose of this study is to determine recommended dose and investigate the efficacy and safety profile of a regimen of nab-PTX plus CBDCA with concurrent thoracic radiotherapy for patients with unresectable non-small cell lung cancer (NSCLC).
Method:
Patients with unresectable stage IIIA or IIIB NSCLC, good performance status, age between 20 and 74 years, and adequate organ function, a relative volume of normal lung receiving a dose of ≥ 20 Gy (V20) ≤35% were eligible. In a phase I study (standard 3+3 design), weekly nab-PTX plus CBDCA was administered intraveneously for six weeks. Doses of each drug were planned as follows: level 1, 40/2; level 2, 50/2 (nab-PTX [mg/m[2]] / CBDCA [area under the plasma concentration time curve (AUC) mg/ml/min]). Concurrent thoracic radiotherapy was administered in 2 Gy fractions to a total dose of 60 Gy. Dose-limiting toxicity (DLT) was observed during concurrent chemotherapy and thoracic radiation and up to 28 days following the end of radiotherapy. After the evaluation of DLT, patients received an additional two cycles of consolidation chemotherapy that consisted of 3-week cycles of nab-PTX (100 mg/m[2] on Days 1, 8 and 15) plus CBDCA (AUC 6 mg/ml/min on Day 1). In a phase II study, we planned to enroll 50 patients treated with recommended dose.
Result:
In a Phase I study, 11 patients were enrolled and received treatment per protocol, with 9 evaluable for efficacy and toxicity. At nab-PTX dose level 1 (40mg/m[2]), none of 3 patients experienced DLT. At nab-PTX dose level 2 (50mg/m[2]), 1 of 6 patients experienced DLT: grade 3 leukopenia requiring a second consecutive skip in the administration of weekly nab-PTX plus CBDCA. The recommended doses (RDs) for the phase II study were nab-paclitaxel 50 mg/m[2] and CBDCA (AUC=2). From October 2015 to November 2016, a total of 52 patients were entered in the phase II portion ( median age, 66 years; age range, 48–74 years; male/female 44/8) .
Conclusion:
Concurrent chemoradiotherapy with nab-PTX 50 mg/m[2] and CBDCA AUC 2 was the recommended dose. We will report the latest efficacy and safety profile of the present therapy. Trial registration: UMIN000012719.
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P2.03 - Chemotherapy/Targeted Therapy (ID 704)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 2
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-009 - Clarification of Mechanisms of Acquired Resistance for Afatinib Using Plasma Samples (ID 7570)
09:30 - 09:30 | Author(s): Kazutoshi Komiya
- Abstract
Background:
It is important to clarification of mechanisms of acquired resistance for epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) to determine the next treatment. EGFR T790M and hepatocyte growth factor (HGF) over expression has been observed in 50 to 60% of lung cancer patients who acquired resistance to the first generation EGFR-TKIs. However mechanisms of acquired resistance for the second generation EGFR-TKI, afatinib have not be clear.
Method:
We analyzed plasma T790M and HGF in twenty lung adenocarcimona patients treated with afatinib. Seven patients treated with afatinib as the first EGFR-TKI treatment and thirteen patients treated as EGFR-TKI re-challenge after acquired resistance for first generation EGFR-TKI. EGFR mutations in plasma DNA were detected using the mutation-biased PCR and quenched probe system. HGF level in plasma was measured by enzyme-linked immunosorbent assay.
Result:
In patients treated with afatinib as the first line treatment, no patients detected plasma T790M before afatinib treatment, but one of seven patients detected plasma T790M at the time of acquired resistance. Five of seven patients detected elevation of plasma HGF level when they had progressive disease. In patients treated with afatinib as EGFR-TKI re-challenge, ten of thirteen patients detected plasma T790M before afatinib treatment and nine of them had also T790M positive at the time of acquired resistance for afatinib. Two of three patients who had not detected plasma T790M before afatinib treatment become plasma T790M positive at the time of acquired resistance. Six patients who detected T790M treated with osimertiib and five of them demonstrated partial response (PR).
Conclusion:
T790M might be also major mechanism of acquired resistance in afatinib. Elevation of plasma HGF level might be detected more high frequency at the time of acquired resistance for afatinib than first generation EGFR-TKIs.
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P2.03-011 - Correlation and Problems of Re-Biopsy and Liquid Biopsy for Detecting T790M Mutation (ID 8039)
09:30 - 09:30 | Presenting Author(s): Kazutoshi Komiya
- Abstract
Background:
T790M mutation test by the approved in vitro diagnostic agent (cobas v2.0) is essential for the use of osimertinib and opportunities for re-biopsy are increasing.
Method:
Success rate and T790M mutation detection rate were retrospectively investigated in 22 cases of 18 patients who took resistance to the 1st and 2nd generation EGFR-TKI at the Saga University Medical School Hospital and underwent re-biopsy. T790M with plasma DNA was examined by MBP-QP, a highly sensitive detection system developed in our laboratory, and cobas v2.0.
Result:
All patients were adenocarcinoma and the mutation status was 8 patients of del 19 and 10 patients of L858R. Re-biopsy sites were 7 bones, 4 primary sites, 3 cases of liver, pleura, lymph nodes, and 2 other sites, respectively, and surgical excision was 31.8%, median time to biopsy from informed consent was 10.5 days (range:1-39). The success rate was 95.5% and the T790M detection rate by cobas v2.0 was 52.3% for all cases, and there was no significant difference between 55.6% for del 19 and 50.0% for L858R. The plasma T790M detection rate using MBP-QP collected at the same time was 65.0% for all cases and there was no significant difference between 55.6% for del 19 and 72.7% for L858R. We experienced one case of atypical angina as a serious complication. Case presentation: ≪No.1≫ First biopsy as re-biopsy (bone): cobas method was negative and MBP-QP method was positive and could not be administered with osimertinib. Second biopsy as re-biopsy (liver): both cobas method and MBP-QP method were positive and could be administered with osimertinib and had a remarkable response. ≪No.2≫ Axillary lymph node biopsies were performed twice, but cobas method was negative and MBP-QP method was positive, and osimertinib could not be administered. Thereafter, hepatic metastasis was biopsied, but both cobas method and MBP-QP method were negative. When plasma specimens by cobas method were tested after insurance approval, plasma T790M was positive, and osimertinib could be finally administered. Although it was effective for axillary lymph node metastases, it had no effect on liver metastases.
Conclusion:
The sensitivity of the test method and the tumor heterogeneity between individuals may influence the detection of T790M mutation. In order to reliably administer osimertinib to patients with indication, it is desirable to establish an appropriate time and site for re-biopsy, and establish examination methods.
