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Marina Chiara Garassino



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    AstraZeneca - Industry Satellite Symposium (ID 42)

    • Event: ELCC 2019
    • Type: Industry Satellite symposium
    • Track:
    • Presentations: 4
    • Moderators:
    • Coordinates: 4/12/2019, 16:30 - 17:30, Room A
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      Considerations for first-line treatment selection for patients with metastatic EGFRm NSCLC (ID 645)

      16:30 - 17:30  |  Presenting Author(s): Marina Chiara Garassino

      • Abstract

      Abstract not provided

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      Panel discussion (ID 681)

      16:30 - 17:30  |  Presenting Author(s): Marina Chiara Garassino

      • Abstract

      Abstract not provided

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      Panel discussion (ID 682)

      16:30 - 17:30  |  Presenting Author(s): Marina Chiara Garassino

      • Abstract

      Abstract not provided

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      Panel discussion (ID 732)

      16:30 - 17:30  |  Presenting Author(s): Marina Chiara Garassino

      • Abstract

      Abstract not provided

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    ESMO Colloquium supported by Lilly Oncology in collaboration with MSD - How to best use immune checkpoint inhibitors in NSCLC: Single agents or combined with chemotherapy? (ID 56)

    • Event: ELCC 2019
    • Type: ESMO Colloquium
    • Track:
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 4/10/2019, 04:45 - 06:15, Room A
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      What is the biological rationale for combining chemotherapy with immune checkpoint inhibitors? (Now Available) (ID 662)

      04:45 - 06:15  |  Presenting Author(s): Marina Chiara Garassino

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    Lunch & Poster Display session (ID 58)

    • Event: ELCC 2019
    • Type: Poster Display session
    • Track:
    • Presentations: 6
    • Now Available
    • Moderators:
    • Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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      101TiP - PACIFIC-R: First real-world study of patients with unresectable, stage III NSCLC treated with durvalumab after chemoradiotherapy (ID 236)

      12:30 - 13:00  |  Author(s): Marina Chiara Garassino

      • Abstract

      Background

      Approximately 30% of patients (pts) with non-small-cell lung cancer (NSCLC) are diagnosed with Stage III disease, which is often unresectable. Historically, the standard of care (SoC) has been platinum-based chemoradiotherapy (CRT), but outcomes have been poor. Durvalumab is a selective high-affinity, human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80. In the phase 3 PACIFIC trial of durvalumab versus placebo in pts with unresectable, Stage III NSCLC without progression after concurrent CRT (cCRT), both primary endpoints progression-free survival (PFS) and overall survival (OS) were met and significantly improved with durvalumab (HR for PFS, 0.52; 95% CI 0.42–0.65; P < 0.001; HR for OS, 0.68; 99.73% CI 0.47–0.997; P = 0.0025) with similar safety between treatments (Antonia et al, NEJM 2017; 2018). Based on these findings, the PACIFIC regimen (durvalumab following CRT) is becoming the SoC. PACIFIC-Real World (PACIFIC-R) will assess if durvalumab treatment after cCRT shows similar efficacy and safety in a large, real-world population.

      a9ded1e5ce5d75814730bb4caaf49419 Trial design

      PACIFIC-R is an international, observational study that will enroll ∼1200 NSCLC pts who have received durvalumab as part of early access programs (EAPs) between Sept 2017 and Dec 2018. In the EAP, eligible pts are adults with histologically or cytologically documented unresectable, Stage III NSCLC, regardless of tumor PD-L1 expression, who have not progressed after definitive CRT. Pts received durvalumab (10 mg/kg intravenously) every two weeks. Pts will be enrolled in the PACIFIC-R study after discontinuation of the EAP in participating countries. Data will be abstracted from pts’ medical records at several time points within the 5 year study period. Primary endpoints are PFS (investigator assessed) and OS. Secondary endpoints include PFS and OS in pt subgroups; time to distant metastases; sites of disease progression; adverse events of special interest leading to treatment interruption, discontinuation or medical intervention; and descriptive analyses of demographic and clinical characteristics of pts treated with durvalumab in a real-world setting. Recruitment for this study is ongoing.

      d9b324a48b043b3d87bc9b3fe620f260 Clinical trial identification

      NCT03798535.

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement

      Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by James King of Cirrus Communications (Macclesfield, UK), an Ashfield company, and was funded by AstraZeneca.

      934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study

      AstraZeneca AB.

      213f68309caaa4ccc14d5f99789640ad Funding

      AstraZeneca AB.

      682889d0a1d3b50267a69346a750433d Disclosure

      N. Girard: Personal fees: AstraZeneca, MSD, BMS, Roche, during the conduct of the study. F. Mornex, D.C. Christoph, R. Fietkau, J. Field, P. Garrido Lopez: Conflict of Interests not immediately avaliable, will be following up with congress directly to provide as soon as possible. A.R. Filippi: Personal fees: AstraZeneca during the conduct of the study. McDonald: Personal fees: AstraZeneca, Elekta; Research grants: MSD, outside the conduct of the study. S. Peters: Personal fees: AbbVie, Amgen, AZ, Bayer, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F Hoffman-LaRoche, Foundation Medicine, Illumina, Janssen, Merck, Merrimack, Novartis, PharmaMar, Pfizer, Regeneron, Sanofi. A.B. Klein, M. Licour: Employment, stock: AstraZeneca outside the conduct of the study. M.C. Garassino: Personal fees: MSD, BMS, AstraZeneca, Roche, outside the conduct of the study.

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      150P - Characterization of patients with metastatic non-small cell lung cancer obtaining long term benefit from immunotherapy (Now Available) (ID 321)

      12:30 - 13:00  |  Author(s): Marina Chiara Garassino

      • Abstract
      • Slides

      Background

      The indications of Immunotherapy (IO) for metastatic Non Small Cell Lung Cancer (mNSCLC) are broadening. Although different studies have proved the efficacy of IO in this setting, only a minority of patients (pts) gains advantage from IO and predictive variables of Long Term Benefit (LTB) are incompletely understood.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      We retrospectively collected data about all consecutive mNSCLC pts treated with IO at Istituto Nazionale dei Tumori, Milan, Italy, from 04/2013 to 07/2017. We defined pts with LTB as those obtaining a Complete Response (CR), a Partial Response (PR) or a Stable Disease (SD) as best response from IO and maintaining it for ≥12 months (mos). Pts were defined to have a Short Term Benefit (STB) if they obtained a CR, a PR or a SD as best response but maintained it for <12 mos. Pts were defined as Progressors (P) If they obtained a progression as best response. Fisher’s test was used to compare variables. Multivariate analyses were performed with logistic regression. Survival was estimated with Kaplan-Meier method.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      One hundred forty-seven pts were identified. IO was an antiPD1 in 87 cases, an antiPDL1 in 52 cases, a combination antiPDL1/PD1 + antiCTLA4 in 7 cases, an antiCTLA4 in 1 case. First line IO was administered in 19 pts, II line IO in 63 pts, ≥III line IO in 64 pts. After a median follow up of 28.5 mos, 35 pts obtained LTB from IO. A higher proportion of LTB pts compared with controls (STB + P) showed CR/PR as first (12/35 vs 10/112, p = 0.0007) and best response (19/35 vs 14/112, p < 0.0001) to IO. More LTB pts than controls had a neutrophil/lymphocyte ratio<5 (p = 0.0378) and did not receive steroids (p = 0.0023), but only the evidence of a CR/PR during IO retained association to LTB at multivariate analyses (p = 0.0002). All other clinical and pathologic variables appeared unremarkable. A second analysis comparing pts with LTB and STB confirmed this result (odds ratio for CR/PR vs SD: 2.629, 95%CI: 1.051-6.579; p = 0.0427).

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      Objective response appears to be a central factor in predicting LTB from IO, irrespective of all other variables. If confirmed, this observation could help in identifying the pts with mNSCLC candidate to gain the highest advantage from IO.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      The authors.

      213f68309caaa4ccc14d5f99789640ad Funding

      Has not received any funding.

      682889d0a1d3b50267a69346a750433d Disclosure

      All authors have declared no conflicts of interest.

      cffcb1a185b2d7d5c44e9dc785b6bb25

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      160P - EPSILoN score: Validation cohort of a prognostic score in advanced non-small cell lung cancer (aNSCLC) patients treated with immunotherapy (Now Available) (ID 494)

      12:30 - 13:00  |  Author(s): Marina Chiara Garassino

      • Abstract
      • Slides

      Background

      Despite the benefit in overall survival (OS), only 18-20% of aNSCLC patients (pts) respond to immunotherapy (IO) in second-line (2nd) with a median progression-free survival (mPFS) of 2-4 months (mo). We previously reported the role of EPSILoN score (Ecog-Ps, Smoke, lIver, Ldh, Nlr) as a clinical and biochemical prognostic score of survival in 154 pts treated with 2nd IO. In this study we aim to validate the EPSILoN score in a different patient population group treated with IO in the same setting.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      We enrolled 193 eligible patients at the National Cancer Institute of Milan, Italy. From 193 aNSCLC patients receiving single-agent anti-PD-(L)-1 as 2nd (61%) and ≥ 3rd line (39%) we collected baseline complete blood cell count and estimated their ratio such as neutrophil-lymphocyte ratio (NLR). Also we evaluated baseline LDH level. Survival analyses using Kaplan–Meier method and multivariate analysis (Cox progression model) were performed to identify and confirm independent variables.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      Of 193 pts mPFS and mOS were 2.3 and 7.6 mo, respectively. Univariate and multivariate analyses for PFS adjusted for age, sex, smoke status, ECOG-PS, histology, disease site, confirmed heavy smoking status (≥40 pack/years) (HR 0.71, p = 0.036) and baseline LDH <400 mg/dl (HR 0.66, p = 0.026) as independent positive factors while ECOG-PS 2 (HR 1.79, p < 0.001), baseline liver mets (HR 1.48, p = 0.04) and NLR≥4 (HR 1.49, p = 0.029) as negative factors. The five baseline clinical and blood biomarkers (smoking status, ECOG PS, liver metastases, LDH and NLR), were included in the EPSILoN score to validate it in this cohort. Finally, three different survival groups defined as high, intermediate and low for PFS (6.0 vs 3.8 vs 1.9 mo respectively, HR 1.94 95% IC 1.51–2.48, p < 0.001) and OS (24.5 vs 8.9 vs 3.4 months, respectively HR 2.40, 95% IC 1.82–3.17, p < 0.001) were identified.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      EPSILoN score which combine five baseline clinical and blood biomarkers may help identify patients who most likely will benefit or not from IO in clinical practice in aNSCLC patients treated with second-line IO. Furthermore, it seems to play an important role in both PFS and OS.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      The authors.

      213f68309caaa4ccc14d5f99789640ad Funding

      Has not received any funding.

      682889d0a1d3b50267a69346a750433d Disclosure

      M.C. Garassino: Consultancies, honoraria: AstraZeneca, Roche, Boehringer Ingelheim, BMS, MSD, Eli Lilly, Novartis, Bayer, Pfizer, Sanofy, Italfarmaco. D. Signorelli: Consultancies, honoraria: AstraZeneca. All other authors have declared no conflicts of interest.

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      188TiP - Metformin &#x0002B;/- cyclic fasting mimicking diet in combination with platinum-pemetrexed chemotherapy for advanced LKB1 inactive lung adenocarcinoma: The FAME trial (Now Available) (ID 497)

      12:30 - 13:00  |  Author(s): Marina Chiara Garassino

      • Abstract
      • Slides

      Background

      LKB1 inactive (LKB1i) lung adenocarcinoma (LA) has an aggressive behavior and is resistant to immunotherapy (IO). LKB1i cells are vulnerable to nutrient starvation. Based on preclinical data showing a synergy cisplatin-metformin, we hypothesized that combining platinum-based chemotherapy (CT) with metformin +/- a calorie-restricted, low-carbohydrate, low-protein diet known as Fasting Mimicking Diet (FMD) may improve the efficacy of CT in patients (pts) with LKB1i LA.

      a9ded1e5ce5d75814730bb4caaf49419 Trial design

      FAME is a monocentric, open label, double arm, non comparative, randomized, single stage, pick-the-winner phase II trial. Primary objective is Progression Free Survival (PFS), evaluated in comparison with a historical cohort of pts treated with CT. Secondary objectives consist in studying experimental treatment toxicity, response rate, overall survival, metabolic changes in blood, urine and stool, correlation between LKB1 mutation status and LKB1 protein expression. Main inclusion criteria are: advanced LKB1i LA, absence of EGFR mutations and ALK/ROS1 rearrangements, PDL1 expression < 50%, performance status 0-1. Main exclusion criteria are: body mass index <20 kg/m2, weight loss ≥5% in the previous 3 months, diabetes mellitus, active brain metastases, baseline fasting glucose ≤65 mg/dL, arterial pO2 <70 mmHg, high blood lactates. Eligible pts will be randomized 1:1 to up to 4 cycles of platinum-pemetrexed CT + metformin, or up to 4 cycles of platinum-pemetrexed CT + metformin + FMD. After 4 cycles, stable/responding pts will continue pemetrexed + metformin until progression or toxicity. Forty-one pts per arm will be necessary to identify a 4.4 mos increase in median PFS. Brookmeyer-Crowley test will be used with an α tail of .15 and a power of .8 mos. Assuming a dropout rate of 5%, the number of pts to enroll will be 88.

      d9b324a48b043b3d87bc9b3fe620f260 Clinical trial identification

      NCT03709147, first posted on 17 October 2018; EudraCT: 2018-000788-95.

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Legal entity responsible for the study

      Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

      213f68309caaa4ccc14d5f99789640ad Funding

      AIRC (Associazione Italiana per la Ricerca sul Cancro) Investigator Grant 2017.

      682889d0a1d3b50267a69346a750433d Disclosure

      All authors have declared no conflicts of interest.

      cffcb1a185b2d7d5c44e9dc785b6bb25

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      23P - Immunosenescence (iSenescence) correlates with progression (PD) to PD-(L)1 inhibitors (IO) and not to platinum-chemotherapy (PCT) in advanced non-small cell lung cancer (aNSCLC) patients (pts) (ID 599)

      12:30 - 13:00  |  Author(s): Marina Chiara Garassino

      • Abstract

      Background

      iSenescence is a remodeling of immune functions with a multifactorial etiology (i.e. aging, chronic inflammation, cancer). Although the absence of CD28 and the expression of CD57 and KLRG1 on circulating T-lymphocytes are hallmarks of iSenescence, the characterization of such phenotype in aNSCLC pts and the correlation with clinical characteristics and benefit from IO or PCT are currently unknown.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      A senescent immune phenotype (SIP) defined as % of circulating CD8+CD28-CD57+KLRG1+ T-lymphocytes was assessed by flow cytometry (FC) on fresh blood from aNSCLC pts treated with IO or PCT in a single institution. A log-rank maximization method was used to identify a SIP cut-off level and dichotomize pts accordingly. The objective was to correlate SIP with clinical characteristics and RECIST response by univariate logistic regression analysis.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      37 aNSCLC pts were evaluable for SIP before IO: 32% ≥ 65 years, 91% non-squamous, 43% KRAS mutated, 51% with PD-L1 expression ≥1%, 8% chemotherapy naïve. 43% had PD, 41% stability (SD), 16% partial response (PR). Median PFS and OS were 2.7 (95% CI 1.8; 7.3) and 13 (95% CI 4.8-NR) months, respectively, median follow-up was 9.3 (95% CI 6.2-14.9) months. SIP (% CD28-CD57+KLRG1+) median value on circulating CD8+ lymphocytes was 12.2% (min 1.7%, max 56.1%). 32% of pts had >20.47% CD8+ lymphocytes with a CD28-CD57+KLRG1+ phenotype, being classified SIP+. SIP status did not significantly correlate with age, pts’ characteristics or CT exposure. 2 (17%) of 12 SIP+ had PR/SD (DCR), vs 19 (76%) of 25 SIP- pts (p = 0.001); median PFS was significantly lower in SIP+ (1.5 months 95% CI 1;2.2) vs SIP- pts (7.4 months 95% CI 5.5, 9.3) (p = 0.001). Among 61 aNSCLC pts treated with 1st line PCT, 18% had PD, 43% SD, 39% PR. SIP median value on circulating CD8+ lymphocytes was 17.9% (min 0.89%, max 66.1%), 43% of pts were SIP+. SIP did not significantly correlate with DCR (OR: 0.82, 95% CI 0.22-3.13, p = 0.82) upon PCT.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      iSenescence, monitored by FC measurement of 3 surface molecules on circulating CD8 + lymphocytes, is observed in 32% and 43% of aNSCLC pts before IO or PCT, respectively. SIP correlated with lower DCR upon IO and not PCT.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      Institut Gustave Roussy.

      213f68309caaa4ccc14d5f99789640ad Funding

      Has not received any funding.

      682889d0a1d3b50267a69346a750433d Disclosure

      All authors have declared no conflicts of interest.

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      82TiP - IMpower030: Phase III study evaluating neoadjuvant treatment of resectable stage II-IIIB non-small cell lung cancer (NSCLC) with atezolizumab (atezo) &#x0002B; chemotherapy (ID 183)

      12:30 - 13:00  |  Author(s): Marina Chiara Garassino

      • Abstract

      Background

      A standard of care for resectable early-stage NSCLC is surgery alone or in combination with adjuvant or neoadjuvant platinum-based doublet chemotherapy (PT-DC). Still, 30%-70% of patients develop recurrence and die from disease progression, highlighting the need for more effective treatments. Atezo, an anti–programmed death-ligand 1 (PD-L1) antibody that restores anti-tumour immunity, has shown promising efficacy as monotherapy and in combination with chemotherapy in advanced NSCLC. It is hypothesised that the combination of atezo and PT-DC may provide clinical benefit in the neoadjuvant setting by enhancing cancer cell killing and eradicating micrometastases, reducing the risk of disease recurrence. The objective of IMpower030 (NCT03456063) is to evaluate the efficacy and safety of atezo in combination with PT-DC as neoadjuvant treatment for patients with resectable early-stage NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Trial design

      IMpower030 is a global, Phase III, double-blind, randomized study in patients with histologically or cytologically confirmed, resectable stage II, IIIA, or select IIIB (T3N2) NSCLC (per AJCC/UICC, 8th ed). Study inclusion requires measurable disease per RECIST v1.1, ECOG PS of 0/1 and eligibility for R0 resection with curative intent and PT-DC. Patients who had received prior therapy for lung cancer or present with nonsquamous NSCLC with activating EGFR mutations or ALK translocation are excluded. Patients will be randomized to receive 4 cycles of neoadjuvant atezo (1200 mg Q3W, Arm A) or placebo (Arm B) in combination with an investigator-selected PT-DC regimen. Following unblinding, patients in Arm A will receive adjuvant atezo treatment for ≤ 16 cycles or until disease recurrence or unacceptable toxicity, and patients in Arm B will receive best supportive care and scheduled observational follow-up. Endpoints will include major pathological response (≤ 10% residual viable tumour tissue at time of resection), investigator-assessed event-free survival and disease-free survival per RECIST v1.1, OS, ORR, pathological complete response and patient-reported outcomes. Exploratory biomarkers will also be evaluated.

      d9b324a48b043b3d87bc9b3fe620f260 Clinical trial identification

      NCT03456063.

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement

      Medical writing assistance for this abstract was provided by Jessica Men, PharmD, of Health Interactions and funded by F. Hoffmann-La Roche, Ltd.

      934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study

      F. Hoffmann-La Roche, Ltd.

      213f68309caaa4ccc14d5f99789640ad Funding

      F. Hoffmann-La Roche, Ltd.

      682889d0a1d3b50267a69346a750433d Disclosure

      S. Peters: Ad board, honoraria: Daiichi, Debiopharm, FoundMed, Janssen, Merrimack, PharmaMar, Regeneron, Sanofi, Seattle Genetics; Ad boad, honoraria, talk: Lilly, Takeda; Talk, honoraria, investigation in trials: AZ, BI, BMS, Clovis; Ad board, honoraria, talk, investigation in trials: Roche, Merck, Novartis, Pfizer; Ad board, honoraria, investigation in trials: Illumina. A.W. Kim: Full-time employee: University of Southern California; Advisory board: Medtronic, Genentech; Other (support of parent study, funding of editorial support): F. Hoffmann-La Roche. B. Solomon: Support of parent study, funding of editorial support: Roche. D.R. Gandara: Research grants: AstraZeneca, Genentech, Novartis, Merck; Consultant/Advisory board: AstraZeneca, Celgene, CellMax, Genentech, Guardant Health, Inivata, IO Biotech, Lilly, Liquid Genomics, Merck, Samsumg Bioepis; Parent study, medical writing support: Roche. R. Dziadziuszko: Advisor/Board member: Roche, Novartis, Pfizer, Boehringer Ingelheim, AstraZeneca, Bristol-Myers Squibb; Speaker’s Bureau: Roche, Pfizer, Foundation Medicine; Support of parent study, funding of editorial support: Roche. A. Brunelli: Support of parent study, funding of editorial support: F. Hoffmann-La Roche. M.C. Garassino: Grants/research support: MSD, BMS, AZ, Roche, Celgene, Medimmune; Advisory board/Speakers’ bureau: MSD, BMS, AZ, Roche, Celgene, Medimmune, Incyte, Ignyta; Other (support of parent study, funding of editorial support): Roche. M. Reck: Speakers bureau, consulting, advisory role: Roche, Lilly, Pfizer, BI, AZ, MSD, BMS, Merck, Novartis, Celgene; Other (support of parent study, funding of editorial support): Roche. L. Wang, I. To, S.W. Sun, B.J. Gitlitz: Employee: Genentech; Other (support of parent study, funding of editorial support): Roche. A. Sandler: Employee: Genetech; Stock: Roche; Other (support of parent study, funding of editorial support): Roche. N. Rizvi: Consulting: AbbVie, AstraZeneca, BMS, EMD Sorono, Genentech, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron; Advisory boards: Bellicum, Brooklyn Immunotherapeutics, Neogenomics, Gritstone; Equity: Bellicum, Brooklyn Immunotherapeutics, Gritstone, ARMO Board of Director (2017-2018) with Stock options vested with company acquisition by Lilly (June 25, 2018); Royalties: Personal Genome Diagnostics: Royalties related to patent filed by MSKCC, Determinants of cancer response to immunotherapy (PCT/US2015/062208); Research funding: BMS, Merck; Institutional financial interests: Clinical research: AstraZeneca, BMS, Genentech, GSK, Merck, Regeneron.

      cffcb1a185b2d7d5c44e9dc785b6bb25

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    Management of side effects and toxicities (ID 22)

    • Event: ELCC 2019
    • Type: Educational session
    • Track:
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 4/11/2019, 14:45 - 16:15, Room A
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      Management of pulmonary toxicities: Clinical case (Now Available) (ID 60)

      14:45 - 16:15  |  Presenting Author(s): Marina Chiara Garassino

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    Medscape Oncology - Industry Satellite Symposium (ID 28)

    • Event: ELCC 2019
    • Type: Industry Satellite symposium
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 4/11/2019, 18:00 - 19:00, Room C
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      Case challenge 1: First-line options - Considerations for treatment choice (ID 636)

      18:00 - 19:00  |  Presenting Author(s): Marina Chiara Garassino

      • Abstract

      Abstract not provided

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      The expanding treatment armamentarium in ALK-positive NSCLC: The evidence (ID 634)

      18:00 - 19:00  |  Presenting Author(s): Marina Chiara Garassino

      • Abstract

      Abstract not provided

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    Mini Oral session II (ID 63)

    • Event: ELCC 2019
    • Type: Mini Oral session
    • Track:
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 4/11/2019, 16:40 - 17:40, Room C
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      85O - Prevalence of programmed death ligand-1 (PD-L1) by demographic, disease and sample characteristics in unresectable, stage III NSCLC (PACIFIC) (Now Available) (ID 305)

      16:40 - 17:40  |  Author(s): Marina Chiara Garassino

      • Abstract
      • Presentation
      • Slides

      Background

      PACIFIC (NCT02125461) was a randomised, placebo-controlled, phase 3 trial evaluating the immune checkpoint inhibitor durvalumab in patients (pts) with unresectable, Stage III non-small cell lung cancer (NSCLC) who did not have disease progression after concurrent chemoradiotherapy (cCRT). Both primary endpoints of progression-free survival and overall survival were met and significantly improved with durvalumab, with similar safety, versus placebo (Antonia et al, NEJM 2017; 2018). We report exploratory analyses of the prevalence of tumour PD-L1 expression by baseline pt, disease and sample characteristics and by response to prior treatment for pts in PACIFIC.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      If available (provision of formalin-fixed paraffin-embedded tumour resection or biopsy samples was optional), archived pre-cCRT tumour tissue was tested retrospectively for PD-L1 tumour cell (TC) expression using the VENTANA PD-L1 (SP263) immunohistochemistry assay and scored at validated pre-specified (≥25%) and post-hoc (≥1%) cutoffs. Overall PD-L1 prevalence (regardless of treatment arm) was summarised by pt subgroups defined by various characteristics, and assessed using a Pearson’s chi-squared test for between-group differences.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      Of 713 randomized pts, 451 (63.2%) were evaluable for PD-L1 status. Among PD-L1-evaluable pts, 67.2% (303/451) had TC ≥ 1% and 35.3% (159/451) had TC ≥ 25% (similar to previous reports in metastatic NSCLC). PD-L1 prevalence by various characteristics at the TC ≥ 1% cut-off are reported in the table.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      There were no important differences noted in PD-L1 prevalence between relevant subgroups at the TC ≥ 1% or TC ≥ 25% cut-offs (latter data to be presented). PD-L1 status was unaffected by sample type or age or biopsy location, suggesting expression is stable from pre-cCRT diagnostic biopsies, and supports the use of either primary tumour or lymph node biopsies for PD-L1 testing.

      b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification

      NCT02125461.

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement

      Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Andrew Gannon of Cirrus Communications, an Ashfield company, and was funded by AstraZeneca.

      934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study

      AstraZeneca.

      213f68309caaa4ccc14d5f99789640ad Funding

      AstraZeneca.

      682889d0a1d3b50267a69346a750433d Disclosure

      D. Planchard: Personal fees: AstraZeneca, Boehringer Ingelheim, BMS, MSD, Pfizer, Novartis, Roche, Celgene, outside the submitted work. M.C. Garassino: Personal fees: AstraZemeca, Roche, BMS, MSD outside the conduct of this study. L. Paz-Ares: Advisory board fees: BMS, Lilly, MSD, AstraZeneca, Roche, Pfizer, Novartis, Incyte, Merk, Boehringer Ingelheim. C. Faivre-Finn: Research funding:AstraZeneca, MSD. A. Spira: Advisory fees, institutional research support: AstraZeneca. Y. Gu, J. Whiteley, M. Scott, J. Walker: Employment, stock: AstraZeneca. C. Wadsworth, P.A. Dennis: Employment, stock: AstraZeneca, outside the conduct of the study. A-M. Boothman: Employment, stock options: AstraZeneca, outside the conduct of the study. M. Ratcliffe: Consultant fees: AstraZeneca, outside the conduct of the study. All other authors have declared no conflicts of interest.

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    Proffered Paper session I (ID 57)

    • Event: ELCC 2019
    • Type: Proffered Paper session
    • Track:
    • Presentations: 2
    • Now Available
    • Moderators:
    • Coordinates: 4/10/2019, 16:30 - 18:15, Room C
    • +

      LBA2 - Patient-reported outcomes (PROs) with durvalumab by PD-L1 expression in unresectable, stage III NSCLC (PACIFIC) (Now Available) (ID 308)

      16:30 - 18:15  |  Presenting Author(s): Marina Chiara Garassino

      • Abstract
      • Presentation
      • Slides

      Background

      In the ph 3 PACIFIC study of Stage III NSCLC pts without progression after cCRT, PFS and OS were significantly improved with durva vs. pbo, with no detrimental effect on PROs. We retrospectively investigated the impact of tumour PD-L1 expression on PROs.

      a9ded1e5ce5d75814730bb4caaf49419 Background

      In the phase 3 PACIFIC study of unresectable, Stage III NSCLC pts without progression after platinum-based concurrent chemoradiotherapy (cCRT), the primary endpoints PFS and OS were significantly improved with durvalumab versus placebo with similar safety and no detrimental effect on PROs. We retrospectively investigated the impact of tumour PD-L1 expression on PROs to better understand the benefit/risk profile of durvalumab across all PD-L1 subgroups.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      After ≥2 cCRT cycles, pts were randomised (2:1) to durva 10 mg/kg or pbo IV q2w up to 12 mo. If available, optional pre-cCRT tumour tissue was tested for PD-L1 tumour cell (TC) expression using the VENTANA SP263 immunohistochemistry assay and scored at pre-specified (25% or unknown) and post-hoc (1%) cutoffs. PROs were assessed using EORTC QLQ-C30 and -LC13 with changes from BL analysed by a mixed model for repeated measures, HRs for time to deterioration (TTD) by a stratified Cox proportional-hazards model, and ORs for improvement rates by logistic regression.

      20c51b5f4e9aeb5334c90ff072e6f928 Methods

      After cCRT with ≥2 chemotherapy cycles, pts were randomised (2:1) to durvalumab 10 mg/kg or placebo IV q2w up to 12 months. If available, optional pre-cCRT tumour tissue was tested for PD-L1 tumour cell (TC) expression using the VENTANA SP263 immunohistochemistry assay and scored at pre-specified (25%) and post-hoc (1%) cutoffs. PROs were assessed using EORTC QLQ-C30 and -LC13 with changes from baseline (BL) analysed by a mixed model for repeated measures, hazard ratios (HRs) for time to deterioration (TTD) by a Cox proportional-hazards model, and odd ratios (ORs) for improvement rates by logistic regression.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      Of 713 pts, 63% had known PD-L1 status. Compliance was high (>80% at Wk 48) across all five PD-L1 subgroups (TC ≥25%, <25%, ≥1%, <1%, and unknown). Most PROs remained stable; however, similar to the ITT population, clinically relevant improvements from BL to Wk 48 were observed for dysphagia and alopecia across most subgroups (4/5 and 5/5, respectively) for durva (mean changes 10.1−20.9 and 15.5−26.9) and all for pbo (10.4−19.4 and 15.8−31.3); plus improvements with pbo for TC ≥25% (12.5 for chest pain and constipation) and TC <25% (10.0 for appetite loss and arm/shoulder pain). Across most subgroups, there were no TTD differences, except those favouring durva: for TC ≥25%, chest pain (HR=0.57), physical functioning (0.60), emotional functioning (0.47), pain (0.56), and haemoptysis (0.42); and, similar to ITT, for TC ≥25%, <25%, ≥1% and <1%, ‘other pain’ (0.60, 0.57, 0.67 and 0.39, respectively). Improvement rates were also similar, except as follows, favouring durva: for TC ≥25%, role functioning (OR=2.84) and, similar to ITT, appetite loss (4.33); for TC ≥1%, diarrhoea (4.50) and haemoptysis (19.34); and, for TC<1%, ‘other pain’ (7.25); for TC<25%, the rate favoured pbo for cough (0.51).

      fd69c5cf902969e6fb71d043085ddee6 Results

      Of 713 pts, 63% had known PD-L1 status. Similar to the intent-to-treat (ITT) population, most PROs remained stable over time from BL across the PD-L1 subgroups (TC ≥25%, <25%, ≥1%, <1%, or unknown), with no clinically meaningful (CM) differences (≥10 points) for durvalumab compared to placebo. However, similar to the ITT population, CM improvements (decreases ≥10 points) from BL to Week 48 were observed for dysphagia and alopecia across most PD-L1 subgroups for both durvalumab (mean changes 8.1 [not CM]−20.9 and 15.5 − 26.9, respectively) and placebo (mean changes 10.4 − 19.4 and 15.8 − 31.3). Pre-specified and post hoc TTD analyses of PROs by PD-L1 subgroup were generally similar to those of the ITT population, with overlapping HR and 95% CIs. Similarly, PRO improvement rates by PD-L1 subgroup were generally similar to those of the ITT population, with overlapping OR and 95% CIs.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      Similar to the ITT population, there were minimal between-Tx differences in PROs based on PD-L1 expression, supporting use of the PACIFIC regimen (durvalumab after cCRT) in all comers.

      b651e8a99c4375feb982b7c2cad376e9 Conclusions

      There were no CM differences in PROs between treatment arms across various PD-L1 subgroups. Results were generally consistent with those in the ITT population, suggesting that PD-L1 expression did not influence PROs in this study.

      b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification

      NCT02125461

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement

      Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Hashem Dbouk, PhD, of Cirrus Communications, an Ashfield company, and was funded by AstraZeneca.

      934ce5ff971f1ab29e840a35e3ca96e9 Editorial acknowledgement

      Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Andrew Gannon of Cirrus Communications, an Ashfield company, and funded by AstraZeneca.

      934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study

      AstraZeneca.

      213f68309caaa4ccc14d5f99789640ad Funding

      AstraZeneca.

      682889d0a1d3b50267a69346a750433d Disclosure

      M.C. Garassino: Personal fees: AstraZeneca, Roche, BMS, MSD. L. Paz-Ares: Advisory fees: BMS, Lilly, MSD, AstraZeneca, Roche, Pfizer, Novartis, Incyte, Merck, Boehringer Ingelheim, outside the conduct of the study. C. Faivre-Finn: Research funding: AstraZeneca, MSD, outside the conduct of the study. A. Spira: Consultant fees, institutional research support: AstraZeneca, outside the conduct of the study. D. Planchard: Personal fees: AstraZeneca, Boehringer Ingelheim, BMS, MSD, Pfizer, Novartis, Roche, Celgene, outside the conduct of the study. M. Ozguroglu: Consultant fees: Astellas; Honoraria: Janssen, outside the conduct of the study. A. Rydén, P.A. Dennis: Employment, stock: AstraZeneca. Y. Zhang, C. O’Brien: Employment, stock: AstraZeneca, outside the conduct of the study. All other authors have declared no conflicts of interest.

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      LBA4 - Effect of post-study immunotherapy (IO) on overall survival (OS) outcome in patients with metastatic (m) NSCLC treated with first-line durvalumab (D) vs chemotherapy (CT) in the phase III MYSTIC study (Now Available) (ID 379)

      16:30 - 18:15  |  Author(s): Marina Chiara Garassino

      • Abstract
      • Presentation
      • Slides

      Background

      In MYSTIC (NCT02453282), an open-label, Phase 3 study of first-line D (anti-PD-L1) ± tremelimumab vs platinum-based CT in mNSCLC, while not statistically significant, a clinically meaningful improvement in OS was seen with D vs CT in pts with tumour cell PD-L1 expression ≥25% (PD-L1 TC ≥25%; HR 0.76 [97.54% CI 0.56–1.02], p=0.036). Here we describe subsequent treatment patterns and explore the effect of subsequent IO on the OS outcome with D vs CT.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      IO/CT-naïve mNSCLC pts were randomised to D (20 mg/kg i.v. q4w until disease progression) or CT (up to 6 cycles; pemetrexed maintenance permitted). In-study crossover from CT to D was not allowed. For D vs CT, the primary endpoint was OS in pts with PD-L1 TC ≥25%. Three statistical models were employed in exploratory analyses to evaluate the effect of subsequent (post-study) IO on the OS data: the rank preserving structural failure time (RPSFT) method, the inverse probability of censoring weighting (IPCW) method, and a 2-stage method.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      163 and 162 pts with PD-L1 TC ≥25% were randomised to D and CT, respectively. At data cut-off (04 Oct 2018), 44.8% of pts in the D arm and 58.6% of pts in the CT arm had received subsequent treatment (Table). Most pts started subsequent treatment within 2 mos of discontinuing study treatment. Among pts who received subsequent treatment, IO was administered to 10/73 (13.7%) pts in the D arm and 64/95 (67.4%) pts in the CT arm; most commonly nivolumab. Using the 2-stage method, which was the most appropriate for evaluating the effect of subsequent IO, OS was improved with D vs CT (HR 0.66 [95% CI 0.51, 0.86]).

      Durvalumab (n=163)Chemotherapy (n=162)
      Pts who received study treatment, n (%)161 (98.8)153 (94.4)
      →Pts who discontinued study treatment136 (83.4)152 (93.8)
      →Pts remaining on study treatment25 (15.3)1 (0.6)
      Pts who received any subsequent treatment, n (%)73 (44.8)95 (58.6)
      →Immunotherapy10 (6.1)64 (39.5)
      →→Nivolumab3 (1.8)50 (30.9)
      →→Pembrolizumab4 (2.5)11 (6.8)
      →→Atezolizumab2 (1.2)3 (1.9)
      →→Durvalumab02 (1.2)
      →→Tremelimumab01 (0.6)
      →→Other immunotherapy1 (0.6)2 (1.2)
      →Cytotoxic chemotherapy70 (42.9)58 (35.8)
      →Other systemic therapies*18 (11.0)18 (11.1)

      Denominators for percentages are the number of pts randomised.

      Excluding immunotherapy and cytotoxic chemotherapy.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      In the MYSTIC study, a markedly higher proportion of pts in the CT arm than in the D arm received subsequent IO, which may have confounded the primary OS outcome. An exploratory analysis showed increased OS benefit with first-line D vs CT after adjusting for the effect of subsequent IO.

      b651e8a99c4375feb982b7c2cad376e9 Editorial acknowledgement

      Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Samantha Holmes, PhD, of Cirrus Communications (Macclesfield, UK), an Ashfield company, and was funded by AstraZeneca.

      934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study

      AstraZeneca PLC.

      213f68309caaa4ccc14d5f99789640ad Funding

      AstraZeneca.

      682889d0a1d3b50267a69346a750433d Disclosure

      N. Reinmuth: Personal fees: BMS, Roche, AstraZeneca, Takeda, Novartis, Boehringer Ingelheim, MSD, Lilly, outside the conduct of the study. B.C. Cho: Grants/research support: Novartis, AstraZeneca, Yuhan, ONO/BMS, MSD, Bayer; Advisor/honoraria fees: AstraZeneca, Roche, Boehringer Ingelheim, Yuhan, BMS, MSD, Novartis; Speaker’s bureau fees: AZ, BMS, MSD, Novartis. J. Schneider: Stock/other ownership: AstraZeneca, Bristol-Myers Squibb, Pfizer, Celgene, Loxo; Consulting/advisory role: Takeda Oncology; Research funding: AstraZeneca, Bristol-Myers Squibb. F.A. Shepherd: Consultancy/advisory role: Lilly, AstraZeneca, Boehringer Ingelheim, Merck Serono; Stock ownership: Lilly, AstraZeneca; Honoraria: Lilly, AstraZeneca, BMS, Roche/Genentech, Merck Sharp & Dohme, Merck Serono, Boehringer Ingelheim; Research funding: Lilly, Pfizer, BMS, AstraZeneca, Roche Canada, Merrimack. S. Peters: Personal fees: AbbVie, Amgen, AZ, Bayer, Biocartis, BI, BMS, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche, Foundation Medicine, Illumina, Janssen, MSD, Merck Serono, Merrimack, Novartis, Pharma Mar, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda; Non-financial support: Amgen, AZ, BI, BMS, Clovis, F. Hoffmann-La Roche, Illumina, MSD, Merck Serono, Novartis, Pfizer. S.L. Geater: Research grants/funding: AstraZeneca, Roche, Novartis. T. Van Ngoc: Research funding: AstraZeneca, GSK, Novartis. M.C. Garassino: Personal fees: Eli Lilly, Boehringer Ingelheim, Otsuka Pharma, AstraZeneca, Novartis, BMS, Roche, Pfizer, Celgene, Incyte, Inivata, Takeda, Tiziana Science, Clovis, Merck Serono, Bayer, MSD, GSK. F. Liu, D. Clemett, P. Thiyagarajah, M. Ouwens, U. Scheuring: Full-time employment: AstraZeneca. N. Rizvi: Advisory boards: AbbVie, AZ, BMS, EMD Serono, Genentech, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Neogenomics, Oncomed, Gritstone, Bellicum; Equity: Oncomed, Gritstone, Bellicum, ARMO; Royalties: PGDX (patent filed by MSKCC). All other authors have declared no conflicts of interest.

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