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
2791 - Efficacy of weekly paclitaxel-bevacizumab combination in advanced non squamous non-small cell lung cancer (NSCLC) : a retrospective multicentric study.
Presenter: Geoffroy Bilger
Session: Poster Display session 1
Resources:
Abstract
2916 - Post progression survival for patients treated with docetaxel/nintedanib in the SENECA trial
Presenter: Enrica Capelletto
Session: Poster Display session 1
Resources:
Abstract
1427 - Final results of randomized phase II trial of metronomic vs weekly oral vinorelbine (OV) as first-line chemotherapy (CT) in advanced NSCLC patients unfit to platinum-based CT (P-CT): Tempo-Lung EudraCT Number: 2014-003859-61
Presenter: Dariusz Kowalski
Session: Poster Display session 1
Resources:
Abstract
3789 - Pioglitazone and clarithromycin combined with metronomic low-dose chemotherapy versus nivolumab in patients with advanced non–small-cell lung cancer treated in 2nd-line and beyond: Outcomes from a randomized phase II trial (ModuLung)
Presenter: Daniel Heudobler
Session: Poster Display session 1
Resources:
Abstract
1519 - Predicting Chemotherapy Toxicity in Elderly Patients with Advanced Non-small Cell Lung Cancer: A Prospective Multicenter Study of the National Hospital Organization in Japan
Presenter: Masaki Kanazu
Session: Poster Display session 1
Resources:
Abstract
1874 - A prospective phase II trial of carboplatin (CBDCA) and nab-paclitaxel (nabPTX) for advanced non-small cell lung cancer (NSCLC) with interstitial lung disease (ILD)
Presenter: Toshiyuki Harada
Session: Poster Display session 1
Resources:
Abstract
3819 - Weekly Epirubicin as palliative treatment in elderly patients with malignant pleural mesothelioma.
Presenter: Paola Candido
Session: Poster Display session 1
Resources:
Abstract
3390 - Survival Prolongation by Rationale INnovative Genomics (SPRING): An international WIN Consortium phase I study exploring safety and efficacy of avelumab, palbociclib, and axitinib in advanced non-small cell lung cancer (NSCLC) with integrated genomic and transcriptomic correlates.
Presenter: Benjamin Solomon
Session: Poster Display session 1
Resources:
Abstract
5069 - Preliminary results from phase 1b study of spartalizumab plus chemotherapy for advanced non-small cell lung cancer (NSCLC)
Presenter: Armando Santoro
Session: Poster Display session 1
Resources:
Abstract
2041 - Efficacy results of selective AXL inhibitor bemcentinib with pembrolizumab following chemo in patients with NSCLC
Presenter: Jose Trigo Perez
Session: Poster Display session 1
Resources:
Abstract