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Ryo Toyozawa
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P75 - Immunotherapy (Phase II/III Trials) - Misc. Topics (ID 248)
- Event: WCLC 2020
- Type: Posters
- Track: Immunotherapy (Phase II/III Trials)
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P75.01 - Activity of Brigatinib in Alectinib-Resistant ALK-Positive NSCLC According to ALK Plasma Mutation Status From J-ALTA Trial (ID 3615)
00:00 - 00:00 | Author(s): Ryo Toyozawa
- Abstract
Introduction
Brigatinib is a selective and potent ALK tyrosine kinase inhibitor (TKI) with preclinical activity against wild-type ALK and a broad spectrum of ALK secondary mutants, known to confer clinical resistance to crizotinib, ceritinib, and alectinib. Brigatinib has shown promising efficacy in Japanese patients with ALK+ NSCLC previously treated with alectinib in a phase 2 trial (J-ALTA). As an exploratory correlative analysis, we examined the relationship of ALK mutation status with brigatinib treatment outcome by NGS analysis of cell free DNA (cfDNA) using plasma specimens at baseline prior to brigatinib treatment (baseline [BL]) in ALK+ NSCLC patients who progressed on alectinib or other ALK TKIs and enrolled in this study.
Methods
Plasma samples were analyzed using the PGDx elioTM plasma resolve (Personal Genome Diagnostics, Baltimore, MD, USA) to determine ALK kinase domain mutations and EML4-ALK fusion status. Brigatinib activity was defined by the confirmed objective response rate (ORR) (RECIST v1.1). Data are reported as of January 22, 2019 for J-ALTA trial.
Results
Of the 72 ALK+ NSCLC patients enrolled, evaluable plasma samples were obtained from 70 patients at BL; alectinib was the most recent ALK TKI (with or without prior crizotinib) in 51 patients. Of these, 30.0% (21/70) of patients had confirmed response to brigatinib, and 35.3% (18/51) of post-alectinib patients responded to brigatinib. Secondary ALK mutations were detected in plasma in 15.7% (11/70) of patients (10 post-alectinib and 1 post-ceritinib). ORR was confirmed in 45.5% (5/11) of these patients. Best responses in patients with secondary ALK mutations were: 5 confirmed partial responses (PRs); 4 stable disease (SD); 2 progressive disease (PD), including 1 confirmed PR and 2 SD in patients with ALK G1202R mutation at BL. No secondary ALK mutations were detected in 84.2% (59/70), ORR was confirmed in 27.1% (16/59) of these. Gene amplification was detected in only 1 patient (MYC gene amplification).
Conclusion
BL EML4-ALK fusion was detected in 51.4% (36/70) of the post-ALK TKIs patients; 25.0% (9/36) of these had secondary ALK mutations. Post-BL samples were also collected from 49 patients at the end of brigatinib treatment. Secondary ALK mutations were detected in 7 patients: 1 with F1174L (also had G1202R at BL); 1 with E1210K (also had I1171S at BL); 5 with G1202R (2 not present at BL; 2 present at BL; 1 present at BL and S1206F also detected). MYC gene amplification was detected in 2 patients.
ALK fusions were detected in the plasma of over 50% of ALK+ NSCLC patients resistant to alectinib and/or other TKIs. Brigatinib demonstrated meaningful activity in ALK TKI-resistant patients regardless of the presence of secondary ALK mutations and EML4-ALK fusion status in plasma. Clinical trial information: NCT03410108.
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P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P76.61 - Long Follow up Study of Comparing Erlotinib (ER) with Gefitinib (GE) for Previously Treated Advanced Non-Small Cell Lung Cancer: WJOG5108LFS (ID 3232)
00:00 - 00:00 | Presenting Author(s): Ryo Toyozawa
- Abstract
Introduction
We reported the results of randomized phase III study comparing GE with ER when they were administered in patients (pts) with previously treated advanced lung adenocarcinoma (WJOG 5108L) in 2016. The data cutoff date of the study was Oct. 28, 2013 and progression free survival time was confirmed in each treatment group. However, confirmation of final overall survival (OS) was not completed because of short follow-up time. Therefore, we conducted a new protocol study, WJOG5108LFS, which followed up the survival of same pts entered on the previous study.
Methods
Survival follow-up was carried out among 536 out of 561 pts (95.5%) who were enrolled WJOG5108L. We calculated Median survival time (MST) and 5-year survival rate of all pts using Kaplan-Myer method and evaluated response rate of brain metastasis in pts of each treatment arm. (UMIN000030082)
Results
The MSTs of all enrolled pts of ER arm (270 pts) and GE arm (266 pts) were 24.34 and 23.85 months (Hazard ratio [HR] 1.012, P=0.8986), respectively. In the subgroup of 353 pts who were positive for activating EGFR mutation, the numbers of ER arm and GE arm were 177 and 176, respectively. The MSTs and 5-year survival rate of ER arm and GE arm were 31.97 and 27.98 months (HR 1.116, P=0.3573) , and 25% and 20%, respectively. The MSTs of exon 19 positive pts of ER arm (99 pts) and GE arm (87 pts) were 37.49 and 28.91 months (HR 1.161, P=0.3757,) and MSTs of L858 positive pts of ER arm (77 pts) and GE arm (87 pts) were 22.21 and 28.16 months (HR 0.931, P=0.6821), respectively. The response rates of brain metastasis in pts with activating mutation positive of ER arm (67 pts) and GE arm (74 pts) were 32.8%, and 22.2% (p=0.160) and MSTs of activating mutation positive pts with brain metastasis for ER and GE were 23.46 and 23.89 months (HR 0.942, P=0.7410), respectively.
Conclusion
The MSTs of all enrolled pts and pts with activating EGFR mutation were not different between ER arm and GE arm. There was also no difference in OS between both arms.
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P85 - Targeted Therapy - Clinically Focused - MET (ID 262)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P85.04 - Capmatinib in Patients with METex14-Mutated Non-Small Cell Lung Cancer: GEOMETRY Mono-1 Asian Subgroup Analysis (ID 3101)
00:00 - 00:00 | Author(s): Ryo Toyozawa
- Abstract
Introduction
Capmatinib was approved for the treatment of adult patients with MET exon 14 skipping (METex14)-mutated, advanced non-small cell lung cancer (NSCLC) based on results from the global phase 2 GEOMETRY mono-1 study (NCT02414139). This sub-analysis compares the efficacy and safety of capmatinib in Asian and non-Asian patients.
Methods
Patients (≥18 years) with ECOG PS 0–1, ALK-/EGFR-wt, and stage IIIB (non-amenable to radical therapy)/stage IV NSCLC were eligible. Patients were assigned to cohorts according to MET status and number of prior lines of therapy and received capmatinib 400 mg twice daily. Efficacy results for Asian and non-Asian patients with METex14-mutated NSCLC assigned to cohorts 4 (1-2 prior lines of treatment) and 5b (treatment-naive) were compared. Safety results from all cohorts were reported. The Asian subgroup included patients enrolled in Japan, South Korea, Singapore, and Taiwan.
Results
At the time of data cut-off (April 15, 2019), 76 patients were included in the Asian subgroup (20 patients with METex14-mutated NSCLC [cohort 4, n=17; cohort 5b, n=3]) and 258 patients were included in the non-Asian subgroup (77 patients with METex14-mutated NSCLC [cohort 4, n=52; cohort 5b, n=25]). 38.2% of patients in the Asian subgroup and 29.1% in the non-Asian subgroup were non-smokers. Median duration of treatment exposure (range) was 11.9 weeks (0.7−124.6) in the Asian subgroup (15.4 weeks [1.4−83.9] for patients with METex14-mutated NSCLC) and 16.1 weeks (0.4−177) in the non-Asian subgroup (34.4 weeks [0.4−108.1] for patients with METex14-mutated NSCLC). Overall response rate among patients with METex14-mutated NSCLC regardless of line of therapy in Asian and non-Asian subgroup was 45% (95% CI: 23.1, 68.5) and 49.4% (95% CI: 37.8, 61.0), respectively. In the Asian subgroup, 2/3 patients from treatment-naive cohort 5b had partial response and 1 patient had stable disease (Table). Capmatinib was found to be safe in both subgroups. The most common treatment-related adverse events (≥20% in the Asian subgroup; any grade) reported in the Asian (n=76) versus non-Asian (n=258) subgroup were increased blood creatinine (36.8% versus 14.3%), nausea (31.6% versus 33.7%), peripheral edema (28.9% versus 45.3%), vomiting (22.4% versus 17.8%), and decreased appetite (21.1% versus 10.1%). Treatment-related adverse events leading to discontinuation were reported in 18.4% of patients in the Asian subgroup and 8.9% of patients in the non-Asian subgroup.
Table: Efficacy as per BIRC assessment
Asian
Non-Asian
Cohort 4
(2/3L)
N=17
Cohort 5b
(1L)
N=3
Cohort 4
(2/3L)
N=52
Cohort 5b
(1L)
N=25
Best overall response, n (%)
Complete response (CR)
Partial response (PR)
Stable disease (SD)
Progressive disease (PD)
Non-CR/Non-PD (NCRNPD)
Not evaluable
0
7 (41.2)
5 (29.4)
2 (11.8)
0
3 (17.6)
0
2 (66.7)
1 (33.3)
0
0
0
0
21 (40.4)
20 (38.5)
4 (7.7)
1 (1.9)
6 (11.5)
1 (4.0)
16 (64.0)
7 (28.0)
1(4.0)
0
0
Overall response rate (CR+PR), % (95% CI)
41.2 (18.4, 67.1)
66.7 (9.4, 99.2)
40.4 (27.0, 54.9)
68.0 (46.5, 85.1)
Disease control rate (CR+PR+SD+NCRNPD), % (95% CI)
70.6 (44.0, 89.7)
100 (29.2, 100)
80.8 (67.5, 90.4)
96.0 (79.6, 99.9)
Conclusion
Capmatinib demonstrated clinically meaningful efficacy and manageable safety profile in Asian patients with METex14-mutated NSCLC, consistent with the results of the overall population in GEOMETRY mono-1 study.
