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A. Inoue
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OA 05 - Next Generation TKI (ID 657)
- Event: WCLC 2017
- Type: Oral
- Track: Advanced NSCLC
- Presentations: 2
- 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)
15:45 - 17:30 | Author(s): A. Inoue
- 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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OA 05.08 - Final Result of Phase I/II Study (AF-001JP) of Alectinib, a Selective CNS-Active ALK Inhibitor, in ALK+ NSCLC Patients (Pts) (ID 9732)
15:45 - 17:30 | Author(s): A. Inoue
- Abstract
- Presentation
Background:
Alectinib (ALC) is a selective, CNS-active ALK tyrosine kinase inhibitor. In two Phase 3 studies (J-ALEX and ALEX), ALC proved superior efficacy and tolerability compared to crizotinib (CRZ). Here we report the final efficacy and safety results of the 46 pts enrolled in the phase II part of study AF-001JP with a longer follow-up period than that observed in J-ALEX and ALEX studies.
Method:
ALC 300 mg b.i.d was given to ALK+ NSCLC pts who were ALK inhibitor-naive and had disease progression after at least one line of chemotherapy to investigate the efficacy and safety until the investigator confirmed no further clinical benefits.
Result:
This study was completed in December 2016. The median treatment duration was 46.1 months (range: 1-62). 20 of 46 pts were on treatment with alectinib at the study termination. Progressive disease (PD) was confirmed in 20 pts (43%). Median PFS was not reached and 4-year PFS rate was 52% (95% CI: 36-66). 14 of 46 pts had CNS metastasis at baseline. Median PFS was 38 months (95% CI: 9-NE) in pts with CNS metastases and was not reached in pts without CNS metastases. Four pts had CNS progression and the 4-year cumulative incidence rate of CNS progression was 9.5%. Median OS was not reached and the 4-year OS rate was 70% (95% CI: 54-81). Safety profile was similar to that reported previously and there were no treatment-related Grade 4 or 5 adverse events for this long administration period.
Conclusion:
Regardless of CNS metastases at baseline, ALC have demonstrated excellent efficacy in ALK+ NSCLC pts without prior ALK inhibitor treatment. ALC was well tolerated over a prolonged administration period.
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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 - 16:00 | Author(s): A. Inoue
- 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.
