1491P - PD-L1 expression in primary tumour vs metastatic samples in the phase III MYSTIC study in first-line metastatic (m) NSCLC

Abstract

Abstract 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 Methods All pts enrolled in MYSTIC were assessed centrally for TC staining for PD-L1 from tissue samples acquired 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.