Abstract 4083
Background
PD-L1 expression determined by immunohistochemistry (IHC) can be a useful biomarker to assess the likelihood of benefit with anti-PD-1/PD-L1 therapies in pts with mNSCLC. Understanding the impact of sample type (primary tumour or metastatic) on predictivity of benefit will inform the suitability of such samples for clinical testing. MYSTIC (NCT02453282) was an open-label, phase III study of durvalumab (D) ± tremelimumab vs chemotherapy (CT) as first-line treatment for mNSCLC; stratification factors for randomisation included tumour cell (TC) PD-L1 expression (≥25% vs < 25%). While not statistically significant, D showed a clinically meaningful improvement in OS compared with CT (HR 0.76 [97.54% CI 0.56–1.02], p = 0.036) in pts with PD-L1 TC ≥25%. We investigated whether the use of a primary tumour or metastatic site biopsy to determine PD-L1 status impacted prevalence of TC ≥ 25% or clinical benefit.
Methods
All pts enrolled in MYSTIC were assessed centrally for TC staining for PD-L1 from tissue samples acquired <3 months prior to randomisation from either the site of the primary tumour or a distant metastasis. Testing was performed using the VENTANA PD-L1 (SP263) IHC assay. A post-hoc analysis evaluated prevalence, OS, ORR and duration of response (DoR) in pts with PD-L1 TC ≥25% as determined using either a primary tumour or a distant metastatic sample.
Results
Of 1118 pts randomised, 716 (64.0%) provided a primary tumour sample and 402 (36.0%) provided a metastatic sample. The prevalence of PD-L1 TC ≥25% assessed using primary vs metastatic samples was 43.0% vs 44.8% (p = 0.569). Outcomes in pts with TC ≥ 25% determined using samples of each type are shown.Table:
1491P
Primary tumour sample PD-L1 TC ≥25% | Metastatic sample PD-L1 TC ≥25% | |||
---|---|---|---|---|
Durvalumab (n = 104) | Chemotherapy (n = 100) | Durvalumab (n = 59) | Chemotherapy (n = 62) | |
Median OS, months | 15.8 | 13.0 | 20.5 | 12.9 |
HR for OS vs CT (95% CI) | 0.81 (0.59–1.11) | - | 0.65 (0.41–1.01) | - |
24-month OS, % | 33.4 | 19.1 | 46.9 | 28.6 |
ORR, % | 30.8 | 37.0 | 44.1 | 38.7 |
Median DoR, months | Not reached | 4.4 | Not reached | 4.1 |
Conclusions
In MYSTIC, PD-L1 TC ≥25% prevalence was similar using primary or metastatic samples. Favourable HRs for OS with D vs CT were seen in pts with TC ≥ 25% expression as determined in either the primary tumour or a metastatic site. Results should be interpreted with caution given the retrospective nature of the analysis.
Clinical trial identification
NCT02453282 (release date: 25 May 2015).
Editorial acknowledgement
Samantha Holmes, PhD, of Cirrus Communications (Macclesfield, UK), an Ashfield company, funded by AstraZeneca and in accordance with Good Publication Practice (GPP3) guidelines.
Legal entity responsible for the study
AstraZeneca PLC.
Funding
AstraZeneca.
Disclosure
N. Reinmuth: Honoraria (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: Bohringer Ingelheim; Honoraria (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Travel / Accommodation / Expenses: MSD; Honoraria (self), Travel / Accommodation / Expenses: Takeda; Honoraria (self): Pfizer. A. Boothman: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. B.C. Cho: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Roche; Advisory / Consultancy: BMS; Advisory / Consultancy, Research grant / Funding (self): Ono; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Yuhan; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Janssen; Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy: MSD; Shareholder / Stockholder / Stock options: TheraCanVac Inc; Honoraria (self), Research grant / Funding (self): Bayer; Honoraria (self), Research grant / Funding (self): MOGAM Institute; Honoraria (self), Research grant / Funding (self): Dong-A ST; Honoraria (self), Research grant / Funding (self), Licensing / Royalties: Champions Oncology; Honoraria (self), Research grant / Funding (self): Dizal Pharma; Honoraria (self), Research grant / Funding (self): MSD. K.H. Lee: Research grant / Funding (institution): AstraZeneca. M. Ahn: Advisory / Consultancy, Research grant / Funding (institution), Spouse / Financial dependant: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): AbbVie; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Research grant / Funding (institution): BIND Biosciences; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer. M. Scott: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. J. Whiteley: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. J. Walker: Full / Part-time employment: AstraZeneca. V. Karwe: Full / Part-time employment: AstraZeneca. P. Mukhopadhyay: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. P. Thiyagarajah: Full / Part-time employment: AstraZeneca. U. Scheuring: Full / Part-time employment: AstraZeneca. N. Rizvi: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Merck; Advisory / Consultancy: Roche; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Lilly; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Merck KGaA; Advisory / Consultancy: Regeneron; Shareholder / Stockholder / Stock options: Gritstone Oncology; Shareholder / Stockholder / Stock options: ARMO Biosciences. All other authors have declared no conflicts of interest.
Resources from the same session
1851 - Nivolumab-induced and radiation recall pneumonitis in patients with non-small cell lung cancer: a multicenter real world analysis of 669 patients
Presenter: Nobuaki Mamesaya
Session: Poster Display session 1
Resources:
Abstract
851 - Retrospective analysis of immunotherapy prognostic scores in advanced NSCLC at Nottingham University Hospitals (UK)
Presenter: Cristina Lopez Escola
Session: Poster Display session 1
Resources:
Abstract
3639 - Applicability of lung immune prognostic index (LIPI) to predict efficacy of first-line pembrolizumab in advanced non-small-cell lung cancer (NSCLC)
Presenter: Xabier Mielgo Rubio
Session: Poster Display session 1
Resources:
Abstract
2950 - Delayed Onset Immune Related Adverse Effects (IRAEs) of Pembrolizumab in Non-Small Cell Lung Cancer
Presenter: Haixi Yan
Session: Poster Display session 1
Resources:
Abstract
3659 - Clinical implication of multiplex IHC and serologic biomarkers on Hyperprogression in NSCLC patients receiving Immune checkpoint blockers in real world.
Presenter: Joori Kim
Session: Poster Display session 1
Resources:
Abstract
4882 - Local ablative treatment and treatment beyond progression for oligo-progression in stage IV non-small cell lung cancer after tumor response to anti-PD1 treatment
Presenter: Florian Guisier
Session: Poster Display session 1
Resources:
Abstract
1358 - Atezolizumab in combination with chemotherapy for first-line treatment of advanced non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials (RCTs)
Presenter: Francis Mogollon-Duffo
Session: Poster Display session 1
Resources:
Abstract
2170 - Prognostic Impact of Metastatic Sites for Pembrolizumab Efficacy as First-line therapy in Patients with PD-L1 tumor proportion score (TPS) ≥ 50% Advanced Non–Small Cell Lung Cancer: A Retrospective Multicenter Study
Presenter: Hayato Kawachi
Session: Poster Display session 1
Resources:
Abstract
3051 - Impact of visceral fat area as independent predictive factor in patients with advanced non-small cell lung cancer treated with nivolumab
Presenter: Yuki Sato
Session: Poster Display session 1
Resources:
Abstract
3409 - Effect and safety of immune checkpoint inhibitors for brain metastases from non-small cell lung cancer
Presenter: Toshihiko Iuchi
Session: Poster Display session 1
Resources:
Abstract