Virtual Library
Start Your Search
N. Nogami
Author of
-
+
Immunotherapy and next-generation TKIs: From second to frontline treatment (ID 55)
- Event: ELCC 2018
- Type: Poster Discussion session
- Track:
- Presentations: 2
- Moderators:P. Garrido Lopez, S. Ekman, S. Ortiz-Cuaran, E. Wauters
- Coordinates: 4/12/2018, 07:45 - 09:00, Room A
-
+
134PD - Primary PFS and safety analyses of a randomized phase III study of carboplatin + paclitaxel +/− bevacizumab, with or without atezolizumab in 1L non-squamous metastatic NSCLC (IMpower150) (ID 469)
07:45 - 09:00 | Author(s): N. Nogami
- Abstract
Background:
Atezolizumab (atezo; anti–PD-L1) inhibits PD-L1 binding to PD-1 and B7.1, restoring anti-cancer immunity. Bevacizumab (bev) may further enhance atezo efficacy by inhibiting VEGF immunosuppression and promoting T-cell tumour infiltration. IMpower150 evaluates the addition of atezo to carboplatin (C) + paclitaxel (P) ± bev in chemo-naive patients (pts) with non-squamous (NSQ) mNSCLC.
Methods:
1202 pts received atezo 1200 mg + C AUC 6 + P 200 mg/m[2] (Arm A) or atezo + bev 15 mg/kg + C + P (Arm B) vs bev + C + P (Arm C) IV q3w for 4 or 6 cycles per investigator (INV) discretion, then maintenance atezo, atezo + bev or bev, respectively. Co-primary endpoints assessed at this data cutoff (15 Sep 2017; minimum follow up, 9.5 mo) were INV-assessed PFS in the ITT-WT (EGFR or ALK negative) population and in WT pts with expression of a tumour T-effector gene signature (Teff-WT; centrally assessed), and OS in the ITT-WT population, for the Arm B vs Arm C comparison. Due to pre-specified statistical testing hierarchy, Arm A vs Arm C has not been formally tested yet.
Results:
356 pts in Arm B and 336 pts in Arm C were enrolled in the ITT-WT. Median age was 63 y; 60% were previous smokers (both arms). 61% and 62% were male, and 39% and 43% had ECOG PS 0 in Arms B and C, respectively. The HRs for INV-assessed PFS in Arm B vs C were 0.62 (95% CI: 0.52, 0.74; P < 0.0001) in the ITT-WT and 0.51 (0.38, 0.68; P < 0.0001) in the Teff-WT populations. Median PFS in Arm B vs C was 8.3 mo vs 6.8 mo and 11.3 mo vs 6.8 mo in the ITT-WT and Teff-WT populations, respectively. PFS benefit was seen regardless of PD-L1 IHC status, including PD-L1–negative pts (TC0/IC0; HR, 0.77 [95% CI: 0.61, 0.99]). Landmark PFS and ORR are shown (Table). Arm B had a comparable safety profile to Arm C; treatment-related serious AEs were 25% vs 19%, respectively.Table:IMpower150 Primary PFS Analysis, Landmark PFS and ORR
HR, hazard ratio; ORR, objective response rate; PFS, progression-free survival; Teff, T-effector; WT, wild-type.aWT populations exclude patients with EGFR or ALK driver mutations.bUnconfirmed ORR.cn = 353 in Arm B and n = 331 in Arm C.dn = 153 in Arm B and n = 127 in Arm C.Arm C (bev + C + P; N = 400) Arm B (atezo + bev + C + P; N = 400) ITT-WT population[a] n = 336 n = 356 Median PFS (95% CI), mo 6.8 (6.0, 7.1) 8.3 (7.7, 9.8) HR (95% CI; P value) 0.62 (0.52, 0.74; P < 0.0001) ITT-WT landmark PFS (95% CI), % 6-month 56% (51, 62) 67% (62, 72) 12-month 18% (13, 23) 37% (31, 42) ORR[b,c] (95% CI), % 48% (43, 54) 64% (58, 68) Teff-WT population[a] n = 129 n = 155 Median PFS (95% CI), mo 6.8 (5.9, 7.4) 11.3 (9.1, 13.0) HR (95% CI; P value) 0.51 (0.38, 0.68; P < 0.0001) Teff-WT landmark PFS (95% CI), % 6-month 57% (48, 66) 72% (65, 79) 12-month 18% (10, 25) 46% (38, 54) ORR[b,d] (95% CI), % 54% (44, 62) 69% (61, 76)
Conclusions:
IMpower150 is the first Phase III study to show a statistically significant and clinically meaningful PFS benefit with atezo + bev + chemo vs bev + chemo in pts with 1L NSQ mNSCLC. Acknowledgement of contribution: G. Finley (Allegheny Cancer Center, Pittsburgh, PA, USA), R. Jotte (Rocky Mountain Cancer Centers, Denver, CO, USA), C. Kelsch, A. Lee, S. Coleman, Y. Shen, M. Kowanetz, A. Lopez-Chavez, A. Sandler (Genentech, Inc., South San Francisco, CA, USA).
Clinical trial identification:
NCT02366143
Legal entity responsible for the study:
F. Hoffmann-La Roche Ltd/Genentech, Inc
Funding:
F. Hoffmann-La Roche Ltd/Genentech, Inc
Disclosure:
M. Reck: Consulting or Advisory Role: Lilly, F.Hoffmann‐La Roche, BI, BMS, MSD, AstraZeneca, Merck, Novartis, Pfizer, Celgene. Speakers’ Bureau: F. Hoffmann‐La Roche, Lilly, Pfizer, BI, AstraZeneca, MSD, BMS, Merck, Novartis, Pfizer, Celgene. M. A. Socinski: Honoraria: Genentech, Speakers Bureau: Genentech, Research Funding: Genentech. F. Cappuzzo: Participation in advisory boards for Roche, AZ, BMS, Takeda, MSD, Lilly, Pfizer. F. Orlandi: Research grants from Astrazeneca, MSD, Genetech-Roche, Advisory tasks for AstraZeneca, Roche, Boehringer Ingelheim, Pfizer. N. Nogami: Honoraria: Meiji Seika Pharma Co., Ltd., AstraZeneca, Pfizer Inc., Bristol‐Myers Squibb, ONO Pharmaceutical CO., LTD., Kyowa Hakko Kirin, Taiho Phamaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd, Eli Lilly Japan, Boehringer Ingelheim. D. Rodríguez-Abreu: Honoraria for lectures and Advisory Board from Bristol-Myers-Squibb, Merck Sharp & Dohme and Hoffmann-La Roche. D. Moro-Sibilot: Advisory boards for Roche, MSD, Pfizer, Novartis, BMS, Astra Zeneca, Lilly. F. Barlesi: Honarium from Genentech & Roche. G. Finley: Promotional speaking on behalf of Bristol Meyers, Boehringer Ingleheim, and Astellas Medivation, and Merck. C. Kelsch: Genentech Employee with Roche Stock. A. Lee: Genentech Employee with Roche Stock. S. Coleman: Genentech Employee with Roche Stock. Y. Shen: Genentech Employee with Roche Stock. M. Kowanetz: Genentech Employee with Roche Stock. A. Lopez-Chavez: Genentech Employee with Roche Stock. A. Sandler: Genentech Employee with Roche Stock. All other authors have declared no conflicts of interest.
-
+
141PD - A prospective study of molecular testing status in the EGFR mutation positive NSCLC patients with disease progression during EGFR TKI treatment (REMEDY study) (ID 167)
07:45 - 09:00 | Author(s): N. Nogami
- Abstract
Background:
Although EGFR tyrosine kinase inhibitors (EGFR-TKI) provide significant clinical benefit in patients with EGFR-mutant non–small cell lung cancer (NSCLC), approximately 50–60% of the patients will acquire resistance by the T790M mutation. Osimertinib is a third generation EGFR-TKI and standard of care for patients whose tumor developed the acquired resistance by T790M mutations during the prior EGFR-TKI treatments. Eligibility for treatment with osimertinib will be dependent on mutation status determined by a validated diagnostic test based on a tumor tissue or a plasma. In order to avoid the risk of false negative, the Japan Lung Cancer Society's guidance on the EGFR mutation test recommends prioritizing tissue sample over plasma sample. Moreover, in case of T790M negative by prior plasma test, it also recommends to re-confirm by tissue test if it can be obtained. We conducted this study to investigate the real world practice of sample collection and T790M testing around the time of plasma testing approval in Japan.
Methods:
This is multicenter collaborative prospective observational study in Japan. Patients diagnosed with EGFR mutation-positive advanced NSCLC and whose progression of the disease (PD) was observed during EGFR-TKI treatment were enrolled. The primary endpoints are 1. the sample collection rate for EGFR T790M mutation test at PD, 2. EGFR T790M gene mutation testing and 3. the EGFR T790M detection rate. In addition, treatment information before and after PD were investigated.
Results:
In previously reported interim analysis of 111 patients, sample collection was performed in 104 cases (93.7%). Regarding collected sample type, tissue sample were collected from 19 patients, cytology sample from 14 patients and plasma sample from 71 patients. EGFR T790M mutation test was conducted in 103 cases (92.8%). T790M mutation detection rate in patients who were obtained adequate tissue sample were 43.8% (7/16) and higher than cytology (21.4%; 3/14) and plasma (22.5%; 16/71). Sixty-one percent (43/71) of the patients tested by plasma were ctDNA “non-shedders” (no detectable EGFR mutation).
Conclusions:
In this presentation, we report final full results of total 243 registered cases.
Clinical trial identification:
UMIN ID; 000024928
Legal entity responsible for the study:
This study was conducted by AstraZeneca KK
Funding:
Has not received any funding
Disclosure:
N. Yamamoto: Personal fees from AstraZeneca, during the conduct of the study; personal fees from Chugai Pharmaceutical, Boehringer Ingelheim, Eli Lilly, and Pfizer, outside the submitted work. N. Nogami: Personal fees from Meiji Seika Pharama., AstraZeneca KK, Pfizer Inc., Bristor-Myers Squibb, ONO Pharmaceutical Co., Ltd, Kyowa Hakko Kirin, TAIHO Pharmaceutical Co., Ltd, CHUGAI Pharmaceutical Co., Ltd, Eliy Lilly Japan and Boehringer Ingelheim. S. Atagi: Personal fees from AstraZeneca KK, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Lilly, Ono and Taiho and contract research with AstraZeneca KK, Boehringer Ingelheim, Chugai, Lilly, Merck Serono, Ono, Pfizer, Taiho and Yakult and consultant fee from AstraZeneca KK. H. Saka: Personal fees from AstraZeneca KK and contract research with AstraZeneca KK. and is a representative of NPO Central Japan Lung Study Group. N. Tashiro: Employee of AstraZeneca KK. T. Seto: Grants(G): Astellas, Bayer, Merck Serono, Novartis, Verastem. Personal fees(PF): BMS, Kissei, Kyowa Hakko Kirin, Nippon Kayaku, Ono, Roche, Sanofi, Showa, Sumitomo Dainippon, Taiho, Takeda and other 3. G and PF: AstraZeneca, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, MSD, BI, Pfizer, Yakult. All other authors have declared no conflicts of interest.
