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M. Ballinger

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Epidemiology and innovations in biomarker development (ID 42)

Event: ELCC 2017
Type: Poster Discussion session
Track:
Presentations: 1

Moderators:P. Boffetta, S. Lantuejoul, R.A. Stahel
Coordinates: 5/06/2017, 16:45 - 17:45, Room W

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96PD_PR - Evaluation of non-classical response by immune-modified RECIST and efficacy of atezolizumab beyond disease progression in advanced NSCLC: Results from the randomized Phase II study POPLAR (ID 363)

16:45 - 17:45 | Author(s): M. Ballinger

Abstract

Background:
Response patterns following cancer immunotherapy (CIT) treatment are often non-classical due to tumor immune infiltration and increase in tumor burden prior to response. As such, RECIST-based endpoints may not adequately predict the potential OS benefit with CIT. In an updated analysis of POPLAR, PFS and ORR improvement with atezolizumab (atezo) vs docetaxel (doc) was restricted to patients (pts) with high PD-L1 expression, whereas OS benefit was seen in the PD-L1–unselected ITT population (HR, 0.69; mOS 12.6 mo vs 9.7 mo with atezo vs doc), suggesting that many pts derive atezo benefit after radiographic progression.

Methods:
287 NSCLC (2L/3L) pts were randomized 1:1 to receive atezo (1200 mg IV q3w) until loss of clinical benefit or doc (75 mg/m[2] IV q3w) until PD per RECIST v1.1 (RECIST). The primary endpoint was OS; secondary endpoints included PFS and ORR per RECIST. Atezo arm pts were evaluated per immune-modified RECIST (imRECIST) and post-PD radiographic changes. Both arms were evaluated for OS post-PD (data cutoff, Dec 1, 2015; minimum follow-up, 20 mo).

Results:
Among 144 pts in the atezo arm, ORR per imRECIST vs RECIST was 17% vs 15%, disease control rate (CR+PR+SD) was 65% (imRECIST) vs 52% (RECIST) and mPFS was 4.3 mo (imRECIST) vs 2.7 mo (RECIST). In 61 atezo pts continuing treatment post-PD, 8% had a subsequent ≥ 30% decrease in target lesions relative to the time of PD, and 74% had a best change between +20% and −30%. mOS post-PD in both arms is shown (Table).

Conclusions:
Increased ORR and PFS per imRECIST vs RECIST in atezo pts highlight the utility of imRECIST as response evaluation criteria to assess efficacy of atezo/CIT. 82% of pts continuing atezo post-PD had subsequent stable ( ≤ +20% change) or decreased target lesions. The nearly 1-yr mOS in pts continuing atezo vs other treatment post-PD is suggestive of atezo benefit lasting beyond PD. Table.rnTable: 96PD_PRrn

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Patients Receiving Therapy Post-PD per RECIST v1.1	n	mOS from time of first RECIST v1.1 PD
Atezo arm pts continuing atezo	61	11.8 mo
Atezo arm pts receiving non-protocol anti-cancer therapy	30	9.2 mo
Doc arm pts receiving non-protocol anti-cancer therapy	46	9.7 mo

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Clinical trial identification:
NCT01903993

Legal entity responsible for the study:
F. Hoffmann-La Roche Ltd/Genentech Inc., a member of the Roche Group

Funding:
F. Hoffmann-La Roche Ltd/Genentech Inc., a member of the Roche Group

Disclosure:
A. Artal-Cortes: Advisory boards for Roche, BMS, MSD and travel fees from Roche. A. Rittmeyer: Grants as an advisor or speaker from Astra Zeneca, BMS, Boehringer Ingelheim, Eli Lilly, Pfizer and Roche Genentech. K. Park: Consulting/advisory from Astellas Pharma, AstraZeneca, BI, Clovis Oncology, Lilly, Hanmi, Kyowa Hakko Kirin, Novartis, Ono Pharmaceutical, Roche; speakers\' bureau fees from BI; research funding from AstraZeneca. C. Lewanski: Consulting/Advisory: Roche, Celgene, Amgen. S. Liu: Employed by Genentech and holds Roche stocks. M. Ballinger: A Genentech employee and has Roche stock. All other authors have declared no conflicts of interest.

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Targeted therapies and immunotherapies (ID 46)

Event: ELCC 2017
Type: Poster Discussion session
Track:
Presentations: 1

Moderators:S. Ekman, N. Reguart
Coordinates: 5/07/2017, 14:45 - 15:45, Room W

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89PD - Results from OAK subgroup analyses: A randomized Phase III study of atezolizumab vs docetaxel in patients (pts) with advanced NSCLC (ID 317)

14:45 - 15:45 | Author(s): M. Ballinger

Abstract

Background:
Atezolizumab (atezo) prevents binding of PD-L1 to its receptors PD-1 and B7.1, restoring tumor-specific T-cell immunity. Primary analysis of the Phase III OAK study in previously treated NSCLC showed superior survival with atezo vs docetaxel (doc) in the ITT population (mOS, 13.8 vs 9.6 months; HR, 0.73) and in pts expressing ≥1% PD-L1 on TC or IC (TC1/2/3 or IC1/2/3; mOS, 15.7 vs 10.3; HR, 0.74). Here we present further subgroup analyses.

Methods:
OAK evaluated atezo vs doc in PD-L1 unselected NSCLC pts who had failed prior platinum-containing chemotherapy. Pts were stratified by PD-L1 expression, prior chemotherapy regimens and histology and randomized 1:1 to atezo (1200 mg) or doc (75 mg/m[2]) IV q3w. PD-L1 expression by IHC and mRNA was centrally evaluated by VENTANA SP142 IHC assay and Fluidigm, respectively. Data cutoff, July 7, 2016.

Results:
In the first 850 of 1225 randomized pts (primary study population), OS was improved with atezo vs doc regardless of histology, and this benefit was seen across PD-L1 subgroups within each histology (Table). Similar OS was seen regardless of PD-L1 expression as assessed by mRNA and IHC. ORR was 14.4% vs 15.2% in non-squamous (non-sq) pts and 11.6% vs 8.2% (atezo vs doc) in squamous (sq) pts. Improved OS was seen with atezo vs doc across subgroups, including pts with treated baseline brain metastases (n = 85; mOS, 20.1 vs 11.9 mo; HR, 0.54; 95% CI, 0.63, 0.89) and never smokers (n = 156; mOS, 16.3 vs 12.6 mo; HR, 0.71; 95% CI, 0.47, 1.08). Further secondary endpoints and exploratory biomarker analyses for these subgroups and by age and EGFR/KRAS status will be presented.

Conclusions:
OAK demonstrated clinically relevant improvements with atezo in the ITT population, including in both histology subgroups, regardless of PD-L1 expression (measured by IHC or tumor gene expression), and among other subgroups, including never smokers and pts with baseline brain metastases.rnTable: 89PDrn

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rn	OS
	Atezo		Doc		HR[a] 95% CI
	n	Median, mo	n	Median, mo	HR[a] 95% CI
Non-sq population
TC3 or IC3	49	22.5	47	8.7	0.35 (0.21, 0.61)
TC2/3 or IC2/3	89	18.7	99	11.3	0.61 (0.42, 0.88)
TC1/2/3 or IC1/2/3	171	17.6	162	11.3	0.72 (0.55, 0.95)
TC0 and IC0	140	14.0	150	11.2	0.75 (0.57, 1.00)
All non-sq	313	15.6	315	11.2	0.73 (0.60, 0.89)
Sq population
TC3 or IC3	23	17.5	18	11.6	0.57 (0.27, 1.20)
TC2/3 or IC2/3	40	10.4	37	9.7	0.76 (0.45, 1.29)
TC1/2/3 or IC1/2/3	70	9.9	60	8.7	0.71 (0.48, 1.06)
TC0 and IC0	40	7.6	49	7.1	0.82 (0.51, 1.32)
All sq	112	8.9	110	7.7	0.73 (0.54, 0.98)

rnaUnstratified HRs.rnTC, tumor cell; IC, tumor-infiltrating immune cell.rn

Clinical trial identification:
NCT02008227

Legal entity responsible for the study:
F. Hoffmann-La Roche Ltd/Genentech Inc., a member of the Roche Group

Funding:
F. Hoffmann-La Roche Ltd/Genentech Inc., a member of the Roche Group

Disclosure:
S.M. Gadgeel: Speaker\'s bureau from Astra-Zeneca, Genentech/Roche and Advisory Boards from Astra-Zeneca, Ariad, Pfizer, Bristol Myers- Squibb and Genentech/Roche. A. Rittmeyer: Grants as an advisor or speaker by Astra Zeneca, BMS, Boehringer Ingelheim, Eli Lilly, Pfizer and Roche Genentech. F. Barlesi: Honarium from Roche. T. Hida: Corporate-sponsored research from Chugai Pharmaceutical. P. He: Employee of Roche/Genentech, and has stocks for Roche and Amgen. Her husband has stocks for Allergan and Gilead. M. Ballinger: Genentech/Roche employee and has Roche stock. D.R. Gandara: Consultant for Genentech and clinical trial grant from Genentech. J. von Pawel: Adboard with fees paid to the institution from AbbVie, Pfizer, Bristol Myers Squibb, and Novartis. All other authors have declared no conflicts of interest.