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A. Bessho
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P2.03a - Poster Session with Presenters Present (ID 464)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03a-028 - Phase I/II Trial of Carboplatin, nab-Paclitaxel and Bevacizumab for Advanced Non-Squamous Non-Small Cell Lung Cancer: Results of Phase I Part (ID 4205)
14:30 - 14:30 | Author(s): A. Bessho
- Abstract
Background:
Nanoparticle albumin-bound paclitaxel (nab-PTX) is a new formulation of paclitaxel and has demonstrated efficacy when combined with carboplatin (Cb), resulting in one of the standard platinum-containing chemotherapy regimens for patients (pts) with chemo-naïve advanced non-small cell lung cancer (NSCLC). The addition of anti-vascular endothelial growth factor antibody bevacizumab (BEV) to chemotherapy has been known an effective treatment option for non-squamous NSCLC. The efficacy and safety of the new triplet regimen: Cb + nab-PTX + BEV has not yet been assessed.
Methods:
We planned multicenter, open-label, phase I/II trial of Cb + nab-PTX + BEV (CARNAVAL study; TORG1424 / OLCSG1402). Eligible pts were chemo-naïve, aged ≥20 years, ECOG PS 0/1 with advanced non-squamous NSCLC. Pts received 4 to 6 cycles of Cb (AUC = 6, day1) + nab-PTX (dose level 1; 100mg/m[2] on days 1, 8 or dose level 2; 100mg/m[2] on days 1, 8, and 15) + BEV (15mg/kg, day1) followed by maintenance nab-PTX + BEV every 3 weeks until disease progression. The phase I part of the study used a 6+6 dose-escalation design to determine the maximum tolerated dose. Major dose-limiting toxicity (DLT) was defined as grade 4 neutropenia for at least 4 consecutive days, febrile neutropenia, grade 4 thrombocytopenia, grade ≥3 non-hematologic toxicity (excluding nausea, vomiting, loss of appetite, fatigue, diarrhea, constipation, disorder of electrolyte, hypertension and hypersensitivity, if they are manageable), and grade 4 hypertension. DLT was assessed during 1st cycle. This study was registered at UMIN (ID: 000014560).
Results:
From October 2014 to July 2015, 4 and 12 pts were enrolled at dose level 1 and 2 cohorts respectively. No DLT was observed at either level and recommended phase II dose (RP2D) was determined at dose level 2. Grade ≥3 adverse events (AEs) during the overall treatment period were as follows; neutropenia (13 pts), thrombocytopenia (4 pts), nausea, vomiting, anorexia (3 pts each), anemia, fatigue, hypertension (2 pts each), pneumonitis, liver disorder, hyponatremia, febrile neutropenia, skin ulcer, esophageal perforation (1 pt each). All AEs were manageable.
Conclusion:
RP2D of Cb + nab-PTX + BEV was determined at dose level 2 (nab-PTX; 100mg/m[2] on days 1, 8 and 15 every 3 weeks). We have started phase 2 part of the trial at dose level 2 since November 2015.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-073 - A Phase II, Liquid Biopsy Study Using Digital PCR in EGFR Mutated, Lung Cancer Patients Treated with Afatinib (WJOG 8114LTR) (ID 4754)
14:30 - 14:30 | Author(s): A. Bessho
- Abstract
Background:
Liquid biopsy is an ideal strategy to monitor mutation status of cancer repeatedly and less invasively. In chronic myeloid leukemia, early remission of mutated cells was reported as a surrogate of longer efficacy. In epidermal growth factor (EGFR) mutated non-small cell lung cancer (NSCLC), to detect resistant mutation (exon20 T790M) during treatment is clinically important because newer tyrosine kinase inhibitors (TKIs) have been developed. Although some reports have mentioned the utility of liquid biopsy in EGFR mutated NSCLC, most were single-institutional, retrospective studies.
Methods:
West Japan Oncology Group (WJOG) 8114LTR is a multi-institutional, prospective liquid biopsy study in advanced NSCLC. Chemotherapy naïve, advanced NSCLC patients with EGFR-sensitizing mutation will receive afatinib monotherapy (40 mg/body) until progressive disease (PD) or unacceptable toxicity. Plasma DNA will be obtained from patients at baseline, 2, 4, 8, 12, 24, 48 weeks, and at PD. Three types of common EGFR mutations (exon 19 deletion, exon 20 T790M and exon 21 L858R) will be analyzed using plasma DNA with multiplexed, pico-droplet digital PCR assay (RainDrop® system, RainDance Technologies, Billerica, MA). Primary endpoint of this study is the concordance of EGFR mutation status between tissue and plasma at baseline. Secondary endpoints are overall response rate, progression-free survival and safety. This is the first report on the primary endpoint and early remission rate based on mutated cf-DNA. This study was registered at UMIN (ID: 000015847).
Results:
Fifty-seven patients were registered and samples from 55 patients were analyzed. Clinical characteristics were as follows; median age: 69 years, male / female: 25/30, PS 0/1: 23/32, c-stage III / IV / post-operative relapse: 2/37/16, exon 19 deletion / exon 21 L858R: 28/27. Sensitivity of plasma sample was 63.6% among overall, while that was 84.6% in patients with distant metastasis. Eighty-two percent of plasma positive patients at baseline showed molecular response in plasma after two weeks of afatinib treatment. De novo T790M mutation was detected in one patient (2%) from plasma samples.
Conclusion:
Liquid biopsy seemed to be suitable especially in patients with distant metastasis. Early molecular remission (within two weeks) was observed in 70% of patients.
