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K. Sugio
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P1.03 - Chemotherapy/Targeted Therapy (ID 689)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.03-004 - Alectinib for Patients with ALK Rearrangement–Positive Non–Small Cell Lung Cancer and a Poor Performance Status (ID 8115)
09:30 - 09:30 | Author(s): K. Sugio
- Abstract
Background:
Alectinib is a potent and highly selective inhibitor of the tyrosine kinase ALK and has shown marked efficacy and safety in patients with ALK rearrangement–positive non–small cell lung cancer (NSCLC) and a good performance status (PS). It has remained unclear whether alectinib might also be beneficial for such patients with a poor PS.
Method:
Eligible patients with advanced ALK rearrangement–positive NSCLC and a PS of 2 to 4 received alectinib orally at 300 mg twice daily. The primary end point of the study was objective response rate (ORR), and the most informative secondary end point was rate of PS improvement. Plasma concentrations of alectinib were measured by liquid chromatography-mass spectrometry (LC-MS/MS).
Result:
Between September 2014 and December 2015, 18 patients were enrolled in this phase II study (Lung Oncology Group in Kyushu 1401). Twelve, five, and one patients had a PS of 2, 3, or 4, respectively, whereas four patients had received prior crizotinib treatment. The median follow-up time for all patients was 9.8 months (range, 5.6 to 18.0 months) at the time of the primary analysis. The ORR was 72.2% (90% confidence interval [CI], 52.9–85.8%), and the disease control rate was 77.8% (90% CI, 58.7–89.6%). The ORR did not differ significantly between patients with a PS of 2 and those with a PS of ≥3 (58.8% and 100%, respectively, P = 0.114). The PS improvement rate was 83.3% (90% CI, 64.8–93.1%, P < 0.0001), with the frequency of improvement to a PS of 0 or 1 being 72.2%. The median progression-free survival (PFS) was 10.1 months (95% CI, 7.1 to17.8 months), with no difference between the patients with a PS of 2 and those with a PS of ≥3 (median PFS, 10.1 and 17.8 months, respectively, P = 0.24). Toxicity was mild, with the frequency of adverse events of grade ≥3 being low. Neither dose reduction nor withdrawal of alectinib because of toxicity was necessary. The trough concentration of alectinib in plasma was 235 ± 65 ng/mL (mean ± SD), which is slightly lower than that previously reported in patients with a good PS, supporting the tolerability of alectinib administration in those with a poor PS.
Conclusion:
Alectinib is a treatment option for patients with ALK rearrangement–positive NSCLC and a poor PS. Updated data and that for overall survival will be available at presentation.
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P2.05 - Early Stage NSCLC (ID 706)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.05-017 - Prognostic Impact of the Clinical T Descriptor in the Eighth Edition of the TNM Staging System of Non-Small Cell Lung Cancer (ID 9494)
09:30 - 09:30 | Author(s): K. Sugio
- Abstract
Background:
The diameter of the solid part of the tumor in a computed tomography (CT) image determines the clinical T descriptor of the new TNM staging system in non-small cell lung cancer (NSCLC). The purpose of this study was to investigate the appropriateness of the clinical T descriptor (cT) in respect to postoperative prognosis.
Method:
This retrospective study included consecutive patients who underwent complete resection in Oita University Hospital between 2006 and 2014 and those who underwent complete resection in Kyushu University hospital between 2003 and 2012. The complete clinical data of 1061 NSCLC patients were available for prognostic analyses. The whole tumor size (TS) in diameter and solid-part size (SPS) in diameter were measured by the thin-section CT image before surgery. The tumors with SPS/TS ratio (STR) = 0, those with 0 < STR < 100, and those with STR = 100 were defined as pure ground glass tumors (GGT), part-solid tumors (PST), and solid tumors (ST), respectively. The survival curves were estimated according to the Kaplan-Meier method and were assessed by the log-rank test.
Result:
The tumors included 809 adenocarcinomas (Ad), 197 squamous cell carcinomas, 31 large cell carcinomas, 18 adeno-squamous cell carcinomas, and 6 other types of tumor. The 5-year survival rate of patients according to the new cT descriptor (version 8) were cTis, 97.6%; cT1mi, 90.7%; cT1a, 87.8%; cT1b, 81.5%; cT1c, 72.8%; cT2a, 69.6%; cT2b, 55.6%; cT3, 55.0%; and cT4, 23.4%. In analyses of Ad patients, the 5-year survival rate of patients according to the whole tumor size were >0 -10 mm, 89.9%; >10 -20 mm, 89.1%; and >20 -30 mm, 84.1%, and that according to the solid part size were 0mm, 97.6%; >0 -10 mm, 91.9%; >10 -20 mm, 84.8%; and >20 -30 mm, 80.8%. The new cT descriptor predicted patient prognosis more effectively than the old cT descriptor of whole tumor size. Postoperative 5-year survivals of the GGT, PST and ST of Ad patients were 97.6%, 89.0%, and 76.3%, respectively (P<.0001). In analyses of the small-size PST (≤ 3 cm), the new cT descriptor did not adequately predict patient prognosis (P=.458).
Conclusion:
The new cT descriptor is a better prognostic indicator than the old cT descriptor in NSCLC. However, patients with small-size PST had a significantly better prognosis than those with ST Ad. Additionally, the new cT descriptor failed to adequately predict the prognoses of the patients with small size PST adenocarcinoma.
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-039 - Acquired Resistance to EGFR-TKI in the Uncommon EGFR Mutation, G719S (ID 8988)
09:30 - 09:30 | Author(s): K. Sugio
- Abstract
Background:
Acquired resistance (AR) to EGFR-TKI is a common event and several mechanisms including T790M, MET amplification, PTEN down regulation have been reported for the common EGFR mutations, Deletion 19 and L858R. An EGFR G719X mutation is an uncommon mutation and is known to show sensitivity to EGFR-TKIs in a series of clinical reports and in experiments using transformed cultured cells. However, there is neither established lung cancer cell line nor resistant cell line reported in the literature, which harbors the EGFR G719X mutation. Here we established a lung adenocarcinoma cell line (G719S-GR) from malignant pleural effusion of a patient whose tumor developed acquired resistance from initial gefitinib treatment.
Method:
G719S-GR cells were established and maintained in RPMI1640 medium supplemented with 10%FBS and 10μM ROCK inhibitor (Y-27632, Wako). The ROCK inhibitor was removed from the medium for the following experiments. Cell growth inhibition was examined with gefitinib, afatinib and osimertinib using CellTiter-Glo (Promega), and a comprehensive genomic analysis was performed using hybrid capture based NGS (NCC oncopanel, Agilent; MiSeq, Illumina) for G719S-GR and MLPA (Salsa, MRC-holland) for clinical samples. Western blot analyses were also performed to identify the mechanism of resistance to gefitinib.
Result:
Cell growth inhibition test revealed EGFR-TKI resistance in G719S-GR cells with LC50 of approximately 20µM for either gefitinib or afatinib, and 2µM for osimertinib, indicating the G719S-GR cells are also resistant to EGFR-TKIs in vitro. From the NGS analysis, G719S-GR cells are proven to harbor EGFR mutations (G719S and E709A) as well as amplification of EGFR, IL7R, MYC and FGFR1 locus. Homozygous deletion of CDKN2A and loss of PTEN, TSC1 were also detected. In order to estimate the mechanism of EGFR-TKI resistance, copy number analyses of several tumor suppressor genes were performed by MLPA using genomic DNA from G719S-GR and tumor biopsy sample (obtained before gefitinib treatment). Losses of CDKN2A, PTEN and TSC1 were confirmed in G719S-GR cells, whereas the loss of PTEN was not observed in gefitinib-naiive tumor sample. Finally, an AKT inhibitor, LY294002 could inhibit the AKT pathway, when it was combined with gefitinib.
Conclusion:
EGFR-TKI resistant mechanisms have not been investigated for uncommon mutations so far. The newly established G719S-GR cell line could be a useful tool for AR mechanism of the G719X mutation, and PTEN loss could be one of the AR mechanism. Further experiments are warranted.
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P3.04 - Clinical Design, Statistics and Clinical Trials (ID 720)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.04-004 - Treatment Rationale and Study Design for the TAKUMI Trial (ID 9691)
09:30 - 09:30 | Author(s): K. Sugio
- Abstract
Background:
50%-60% of patients after the first-generation EGFR-TKI, gefitinib and erlotinib showed acquired resistance of T790M mutation and osimertinib is a standard regimen for this population. However, the median PFS by osimertinib alone is 8-10M and a better strategy is needed. One promising option is a combination of osimertinib and chemotherapy, and previous trials have suggested the promising efficacy by the combined treatment of EGFR-TKI with pemetrexed. We here present the treatment rationale and study design of TAKUMI trial, a multicenter randomized phase Ⅱ study of of osimertinib (Tagrisso) alone versus osimertinib plus carboplatin/pemetrexed for patients with locally advanced or metastatic non-small cell lung cancer whose disease has progressed with previous epidermal growth factor receptor tyrosine kinase inhibitor therapy and whose tumours harbour a T790M mutatIon within the epidermal growth factor receptor gene.
Method:
Figure 1schema of this study
Result:
Section not applicable
Conclusion:
Section not applicable
