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Y. Fujita
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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): Y. Fujita
- 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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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): Y. Fujita
- 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: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-010 - Updated Survival Outcomes of NEJ005/TCOG0902, a Randomized PII of Gefitinib and Chemotherapy in EGFR-Mutant NSCLC (ID 7948)
09:30 - 09:30 | Author(s): Y. Fujita
- Abstract
Background:
North East Japan Study Group (NEJ) 005/ Tokyo Cooperative Oncology Group (TCOG) 0902 study has demonstrated that first-line concurrent (C) and sequential alternating (S) combination therapies of EGFR tyrosine kinase inhibitor (gefitinib) plus platinum-based doublet chemotherapy (carboplatin/pemetrexed) offer promising efficacy with predictable toxicities for patients with EGFR-mutant NSCLC (ASCO2014, Ann Oncol 2015). However, overall survival (OS) data were insufficient because of the lack of death events in the primary report.
Method:
Progression-free survival (PFS) and OS were re-evaluated at the final data cutoff point (March 2017) for the entire population (N = 80).
Result:
At the median follow-up time of 35.6 months, 88.8% of patients had progressive disease and 77.5% of patients had died. Median PFS was 17.5 months for the C regimen and 15.3 months for the S regimen (p = 0.13). Median OS time was 41.9 with the C regimen and 30.7 months with the S regimen (p = 0.036). Updated response rates were similar in both groups (90.2% and 82.1%, respectively; p = 0.34). Patients who had common mutations showed no significant differences in PFS according to type of mutation. Patients with Del19 displayed relatively better OS (median: 45.3 and 33.3 months for C and S regimens) than those with L858R (31.4 and 28.9 months). No severe adverse events including interstitial lung disease have occurred during the follow-up period since the primary report. In an exploratory analysis, there was no significant difference in post progression survival and overall survival between patients with progression of target or non-target lesions and those progressed with new lesions.
Conclusion:
This updated analysis has confirmed that PFS is improved with first-line combination therapies compared to that with gefitinib monotherapy, and the C regimen in particular offers an overall survival benefit of 42 months in the EGFR-mutated setting. Our on-going NEJ009 study will clarify whether this combinational strategy can be incorporated into routine clinical practice.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-072 - Dacomitinib Versus Gefitinib for First-Line Treatment of Advanced EGFR+ NSCLC in Japanese Patients (ARCHER 1050) (ID 8476)
09:30 - 09:30 | Author(s): Y. Fujita
- Abstract
Background:
Second-generation EGFR tyrosine-kinase inhibitor dacomitinib has shown encouraging activity as first-line therapy in patients with EGFR-activating mutation-positive (EGFR[+]) advanced NSCLC. We performed the first randomized, open-label phase 3 trial comparing dacomitinib with gefitinib as first-line therapy (NCT01774721) which demonstrated a clinically meaningful and statistically significant benefit of dacomitinib versus gefitinib (PFS per IRC: HR, 0.59 [95%CI, 0.47–0.74]; 1-sided P<0.0001; median PFS, 14.7 vs 9.2 months). We present results from Japanese patients enrolled in this ongoing study.
Method:
Patients with newly diagnosed stage IIIB/IV recurrent NSCLC harboring an EGFR-activating mutation (exon 19 deletion or exon 21 L858R ± exon 20 T790M) were randomized 1:1 to once-daily oral dacomitinib 45 mg or gefitinib 250 mg until disease progression or discontinuation. Patients with CNS mets excluded. Stratification was by race and EGFR mutation subtype. The primary endpoint was progression-free survival (PFS) per blinded independent review committee (IRC).
Result:
Among 452 patients enrolled in ARCHER 1050, 81 were Japanese. Slight imbalances in baseline characteristics were observed (Table). PFS and duration of response improvement in Japanese patients was consistent with global results.
Objective response rates per IRC were similar (dacomitinib, 75.0% [95%CI, 58.8–87.3]; gefitinib, 75.6% [95%CI, 59.7–87.6]; 2-sided P=0.9579). Overall survival data are not mature. All 81 patients received study treatment. No grade 4/5 adverse events (AEs were observed with dacomitinib, while 3 grade 4 AEs and 1 grade 5 AE (disease progression) occurred with gefitinib. The most common grade 3 AEs were dermatitis acneiform (27.5%) and paronychia (22.5%) with dacomitinib and alanine aminotransferase increased (12.2%) and abnormal hepatic function (7.3%) with gefitinib. No new safety signals were identified.Japanese Intention-to-Treat Population Dacomitinib (n = 40) n (%) Gefitinib (n = 41) n (%) Unstratified HR [95% CI] 1-sided p-value Male 15 (37.5) 20 (48.8) Age, years <65 ≥65 19 (47.5) 21 (52.5) 15 (36.6) 26 (63.4) Smoking status Never smoked Ex-smoker Smoker 19 (47.5) 20 (50.0) 1 (2.5) 24 (58.5) 16 (39.0) 1 (2.4) ECOG PS 0 1 28 (70.0) 12 (30.0) 21 (51.2) 20 (48.8) Median, months Median, months PFS per IRC 18.2 (95% CI, 11.0–31.3) 9.3 (95% CI, 7.4–14.7) 0.54 (95% CI, 0.31–0.95) P=0.0141 PFS per INV 18.3 (95% CI, 14.6–22.1) 10.2 (95% CI, 7.3–16.9) 0.61 (95% CI, 0.36–1.04) P=0.0334 DoR per IRC in responders # of responders=30 17.5 (95% CI, 10.2–34.3) # of responders=31 8.3 (95% CI, 5.6–12.9) 0.44 (95% CI, 0.22–0.84) P=0.0056 CI, confidence interval; DoR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; INV, investigator assessment.
Conclusion:
Dacomitinib significantly improved PFS and duration of response over gefitinib in first-line treatment of Japanese patients with advanced EGFR[+] NSCLC, with a manageable safety profile.
