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H. Nokihara
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MA 16 - Mediastinal, Tracheal and Esophageal Tumor: Multimodality Approaches (ID 675)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:K. Shibuya, Francoise Mornex
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 313 + 314
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MA 16.04 - Phase II Trial of S-1 Treatment as Palliative-Intent Chemotherapy for Previously Treated Advanced Thymic Carcinoma (ID 8627)
16:00 - 16:05 | Author(s): H. Nokihara
- Abstract
- Presentation
Background:
Thymic carcinoma (TC) is a rare cancer with minimal evidence of survival with palliative-intent chemotherapy. Sunitinib and everolimus monotherapies have been proposed as active molecular-targeted approaches based on phase II (Ph II) trials, and S-1, an oral fluoropyrimidine, has been described in the NCCN guideline as an active cytotoxic agent for refractory TC based on a case series. Therefore, we conducted a Ph II trial to study the result of S-1 treatment in patients with refractory TC.
Method:
In this Ph II study performed at three cancer centers in Tokyo, we aimed to enroll 26 TC patients previously treated with platinum-based chemotherapy. The patients received S-1 orally twice daily at a dose of 40–60 mg/m2 for 4 weeks, followed by 2 weeks off until progressive disease or unacceptable toxicities. S-1 was used off-label. The primary end-point was determining the objective response rate, and secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicities.
Result:
Twenty-six patients (10 males) were recruited between November 2013 and May 2016. The median age was 63 (27–74) years. Among the 26 patients, 23 had squamous cell carcinoma histology and 10 had an ECOG performance status of 0. Additionally, one patient showed complete response and seven patients showed partial responses, resulting in a 30.8% response rate (95% confidence interval [CI], 16.5–50.0) and a 65.4% disease control rate (95% CI, 46.2–80.6). After a median follow-up of 13.4 months, the median PFS was 4.3 months (95% CI, 2.3–7.6 months) and median OS was 23.4 months (95% CI, 12.8–not reached). Treatment-related adverse events (AEs) of grade ≥3 included neutropenia (12%), skin rash (8%), elevated ALT, decreased WBC count, and fatigue (4%). No treatment-related death was observed. However, treatment was discontinued in three patients (12%) because of AEs.
Conclusion:
S-1 for refractory TC confirmed clinical activity with good tolerability. Clinical trial identification: UMIN000010736
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OA 05 - Next Generation TKI (ID 657)
- Event: WCLC 2017
- Type: Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:James Chih-Hsin Yang, Fiona Blackhall
- Coordinates: 10/16/2017, 15:45 - 17:30, Room 301 + 302
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OA 05.03 - Clinical Activity of ASP8273 in Asian Non-Small Cell Lung Cancer Patients with EGFR Activating and T790M Mutations (ID 7889)
16:05 - 16:15 | Author(s): H. Nokihara
- Abstract
- Presentation
Background:
Epidermal growth factor receptor (EGFR) activating mutations confer sensitivity to tyrosine kinase inhibitor (TKI) treatment for non-small cell lung cancer (NSCLC) and occur in ~50% of East Asian patients with NSCLC. While initial TKI treatment can be effective, acquired resistance inevitably develops with a secondary mutation (T790M). ASP8273 is a highly specific, irreversible, once-daily, oral, EGFR TKI which inhibits both activating (eg, exon 19 deletions, L858R) and resistance (eg T790M) mutations.
Method:
This dose-escalation/dose-expansion study (NCT02192697) was conducted in two phases. In Phase 1, adult Japanese patients (≥20 yr) with NSCLC previously treated with ≥1 EGFR TKI were enrolled and received escalating ASP8273 doses (25–600mg) to assess safety/tolerability as well as to determine maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D). In phase 2, adult T790M-positive NSCLC patients in Japan, Korea, and Taiwan were enrolled to further define the ASP8273 safety/tolerability profile at RP2D and determine antitumor activity (assessed using RECIST v1.1). Antitumor activity in phase 2 was evaluated according to Simon’s 2-stage design (uninteresting response=0.3, desired response=0.5, α=0.05, β=0.1). If ≥9 of 24 ASP8273-treated patients achieved a desired response in the first stage, then 39 additional patients would be enrolled. If ≥ 25 of the 63 total patients achieved response, ASP8273 would be considered to have antitumor effects.
Result:
A total of 123 patients (n=47 phase 1; n=76 phase 2) were enrolled. In both phases, more women were enrolled. The median age was 65 years in phase 1 and 63 years in phase 2. Based on phase 1 findings, MTD and RP2D were 400mg and 300mg, respectively. As 27 of the 63 patients treated with ASP8273 300mg in the first and second stages combined achieved a clinical response (based on independent central review), ASP8273 was determined to have antitumor activity (ORR=42.9%; 95% CI: 30.5–56.0). The ORR at week 24 in all patients in the full analysis set was 42.1% (n=32/76; 95% CI: 30.9, 54.0). The median duration of PFS (central review) was 8.1 months (95%CI: 5.6,--). The most commonly reported treatment-emergent AEs (TEAE) in phase 2 were diarrhea (n=50/76), nausea (n=31/76), increased alanine aminotransferase (n=27/76), decreased appetite and vomiting (n=26/76 each), and hyponatremia (n=25/76). Drug-related TEAEs were reported in 93.4% (n=71/76) of patients, the most common of which was diarrhea (n=43/76).
Conclusion:
ASP8273 was generally well tolerated and demonstrated antitumor activity in Asian patients with both EGFR activating and T790M mutations.
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P2.07 - Immunology and Immunotherapy (ID 708)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.07-011 - Long Follow up from Phase I Study of Nivolumab and Chemotherapy in Patients with Advanced Non-Small-Cell Lung Cancer (ID 8156)
09:30 - 09:30 | Author(s): H. Nokihara
- Abstract
Background:
This phase I study investigated the tolerability, safety and pharmacokinetics of nivolumab in combination with chemotherapy in Japanese patients with advanced non-small-cell lung cancer (NSCLC).
Method:
Patients who have stage IIIB without indication for definitive radiotherapy, stage IV，or recurrent NSCLC were eligible. nivolumab (10 mg/kg，day 1) and chemotherapy [arm A: cisplatin (80 mg/m[2], day 1) / gemcitabine (1250 mg/m[2], day 1 and 8), arm B: cisplatin (75 mg/m[2], day 1) / pemetrexed (500 mg/m[2], day 1), arm C: carboplatin (AUC 6, day 1) / paclitaxel (200 mg/m[2], day 1) / bevacizumab (15 mg/kg, day 1), arm D: docetaxel (75 mg/m[2], day 1)] were administered every three weeks. Arm A and B were administrated for four cycles and arm C was for four to six cycles as first-line chemotherapy. After that, nivolumab in arm A, nivolumab / pemetrexed in arm B, and nivolumab / bevacizumab in arm C were continued every three weeks as maintenance therapy until disease progression. Arm D were administrated until disease progression as second-line chemotherapy.
Result:
Six patients each in four arms, total 24 patients were enrolled. Median follow-up time was 20.4 months. Progression free survival [median (range)] were 6.3 (0.7-42.2+) months in arm A, 11.8 (1.4-47.4+) months in arm B, 40.7 (5.3-43.5+) months in arm C, and 3.2 (1.9-10.9) months in arm D. Three-year progression-free survival rates were 20% in arm A, 16,7% in arm B, 62.5% in arm C, and 0% in arm D.
Conclusion:
nivolumab 10 mg/kg showed acceptable toxicity profile and encouraging antitumor activity in combination with chemotherapies in Japanese patients with advanced NSCLC. Especially, arm C showed favorable response rate and long progression free survival in this study.
