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S. Wang

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    MA 10 - Immunotherapy I (ID 664)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Immunology and Immunotherapy
    • Presentations: 12
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      MA 10.01 - Durvalumab ± Tremelimumab with Platinum-Doublets in Non-Small Cell Lung Cancer: Canadian Cancer Trials Group Study IND.226 (ID 8700)

      11:00 - 12:30  |  Presenting Author(s): Desiree Hao  |  Author(s): R.A. Juergens*, S.A. Laurie, P.M. Ellis, M. Mates, Penelope Bradbury, M. Tehfe, C. Kollmannsberger, A. Arnold, John R Goffin, P. Wheatley-Price, J. Hilton, A.G. Robinson, D. Tu, P. Brown-Walker, L. Seymour

      • Abstract
      • Presentation
      • Slides

      Background:
      Anti-PD1-monotherapy has activity in NSCLC with improved outcomes compared to chemotherapy. Preclinical, and early clinical data, suggests that combining immune checkpoint inhibitors and platinum-based chemotherapy may be synergistic. We examined the cohort of patients (pts) with metastatic NSCLC, with no prior therapy for advanced disease, from this multicentre phase Ib trial. The primary objective was to establish the recommend phase II doses of durvalumab (Du) ± tremelimumab (Tr) in combination with platinum-doublet chemotherapy. Secondary objectives included assessing safety, tolerability, and antitumour activity of the 4-drug combination.

      Method:
      Pts were treated with Du±Tr at one of 4 dose levels (DL) concomitantly with either pemetrexed (Pem) +cisplatin/carboplatin followed by maintenance Pem for nonsquamous histology or gemcitabine (Gem) +cisplatin/carboplatin for squamous tumours. At DL0 Du 15 mg/kg IV q3wks was added; DL1 added Du 15mg/kg q3wk + Tr 1mg/kg x1 dose; DL2a added Du 15mg/kg q3wk + Tr 1 mg/kg q6wk x multiple doses; DL2b added Du 15mg/kg q3wk + Tr 3 mg/kg q6wk (1 dose with cycle 1 and 2 doses with maintenance pem), DL3 and DL4 added a fixed doses of Du 1125mg/Tr 56 mg and Du 1500 mg/ Tr 75 mg q3wk respectively. Du could continue until 1 year or unacceptable toxicity.

      Result:
      To date, 45 pts (median age=62 (range 36-78); 44% male, 100% ECOG PS≤1) have received 346 cycles in the Pem-platinum cohort while 9 pts (median age=64 (range 57-80); 78% male, 100% ECOG PS≤1) have been received 55 cycles in the Gem-platinum group. Most adverse events were ≤grade 2 and attributed to chemotherapy. Immunotherapy-related adverse events (irAEs) ≥ grade 3 were observed in 27% of patients and were more commonly reported with the addition of Tr. In the Pem-platinum cohort, diarrhea (n=5), fatigue (n=4) and elevated lipase (n=4) were the most come irAEs ≥ grade 3, while rash, pneumonitis and hypothyroidism occurred in 1 pt each after the introduction of Tr. In the Gem-platinum cohort, irAEs ≥ grade 3 were fatigue and rash (1 pt each at DL2b) and elevated lipase (1 pt at DL3). The objective response rate in 35 evaluable patients receiving Pem-platinum was 57.1% (95% CI=39.4, 73.7 ) and 37.5% (95% CI=8.5, 75.5) in the 8 evaluable patients receiving Gem-Platinum.

      Conclusion:
      The combination of Du±Tr can be safely administered with platinum-doublet chemotherapy with encouraging preliminary response data. Adding Tr may increase ≥ grade 3 irAE hence patient selection and early intervention is key to managing irAEs. *contributed equally

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      MA 10.02 - Nab-Paclitaxel + Durvalumab as Second- or Third-Line Treatment of Advanced NSCLC: Results from ABOUND.2L+ (ID 8682)

      11:00 - 12:30  |  Presenting Author(s): Ramaswamy Govindan  |  Author(s): Manuel Cobo Dols, S.P. Aix, Pieter E. Postmus, C. Lewanski, Jaafar Bennouna, J.R. Fischer, O.J. Vidal, David James Stewart, A. Ardizoni, J. Weaver, M. Wolfsteiner, Martin Reck, D. Talbot, D. Morgensztern, T.J. Ong

      • Abstract
      • Presentation
      • Slides

      Background:
      Chemotherapy may enhance immunotherapeutic effects by causing tumor antigen release, which primes the immune system to kill tumor cells. Early clinical data on nab-paclitaxel + carboplatin in combination with immune checkpoint inhibitors (ICI) demonstrated promising activity without compounding toxicities in patients with non-small cell lung cancer (NSCLC). ABOUND.2L+ evaluated nab-paclitaxel–based regimens in previously treated patients with advanced NSCLC. Here we report the efficacy and safety of nab-paclitaxel + durvalumab as second/third-line treatment.

      Method:
      Patients with advanced NSCLC were assigned to receive second/third-line (immunotherapy allowed in prior line, including platinum doublet combination) nab-paclitaxel 100 mg/m[2] on days 1 and 8 + durvalumab 1125 mg on day 15, in 21-day cycles, administered until unacceptable toxicity/progression per immune-related RECIST v1.1. Primary endpoint is progression-free survival (PFS). Secondary endpoints are overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety.

      Result:
      Seventy-nine patients were enrolled. Median age was 63 years, 68% of patients were male, 23% had Eastern Cooperative Oncology Group performance status of 0, and 70% had nonsquamous NSCLC; 11% of patients received prior ICIs. Median PFS (Table) and OS were 4.5 (3.4-5.8) months and NE (7.3-NE). ORR was 27% (1 complete response) and DCR was 71%. Grade 3/4 treatment-emergent adverse events of special interest occurring in ≥ 5% of patients included neutropenia (6%) and dyspnea (5%); grade 3/4 peripheral neuropathy and anemia each occurred in 4% of patients. Median treatment duration was 24 weeks; median number of treatment cycles was 7. For nab-paclitaxel and durvalumab, median dose intensities were 59.05 mg/m[2]/week and 326.61 mg/week, respectively; median percentages of per-protocol dose were 88.58% and 87.10%.

      Conclusion:
      The combination of durvalumab with nab-paclitaxel demonstrated antitumor activity with manageable toxicity in the second/third-line setting. Further details will be presented. NCT02250326

      Nab-P Durva Median PFS (range), months
      Overall (n = 79) 4.5 (3.4-5.8)
      ICI pretreated (n = 9)[a] ICI naive (n = 69)[a] 6.9 (1.4-NE) 4.4 (3.0-5.7)
      Squamous (n = 23)[a] Nonsquamous (n = 55)[a] 5.9 (3.0-7.8) 4.2 (2.9-5.7)
      ICI, immune checkpoint inhibitor; NE, not estimable; PFS, progression-free survival. [a] Data pending for 1 patient.


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      MA 10.03 - 3-Year Survival and Duration of Response in Randomized Phase II Study of Atezolizumab vs Docetaxel in 2L/3L NSCLC (POPLAR) (ID 8703)

      11:00 - 12:30  |  Presenting Author(s): Keunchil Park  |  Author(s): C. Lewanski, Shirish M Gadgeel, L. Fehrenbacher, Julien Mazieres, A. Rittmeyer, Ji-Youn Han, A. Artal-Cortes, F. Braiteh, M. Gandhi, W. Yu, C. Matheny, P. He, A. Sandler, M. Ballinger, Johan F. Vansteenkiste

      • Abstract
      • Presentation
      • Slides

      Background:
      Atezolizumab (anti–PD-L1) has demonstrated OS benefit over docetaxel in a randomized Phase II study, POPLAR, in patients with advanced NSCLC. This benefit has been confirmed in the randomized Phase III study OAK (Rittmeyer, 2017). The 3-year survival analysis of the POPLAR study presented here describes the longest survival follow-up reported to date of an all-comer randomized PD-L1/PD-1 immunotherapy trial in 2L+ NSCLC.

      Method:
      Patients were randomized 1:1 to receive atezolizumab (1200 mg) or docetaxel (75 mg/m[2]) IV q3w. Tumors were prospectively evaluated for tumor cell (TC) or tumor-infiltrating immune cell (IC) PD-L1 expression using the VENTANA SP142 IHC assay. Landmark OS was estimated using the Kaplan-Meier method. Data cutoff, April 7, 2017; minimum follow-up, 3 years.

      Result:
      The 2-year and 3-year survival with atezolizumab vs docetaxel were 32.2% vs 16.6% and 18.7% vs 10.0%, respectively. The long-term OS benefit of atezolizumab vs docetaxel was observed across histology and PD-L1 expression subgroups (Table). While the TC3 or IC3 subgroup derived the greatest OS benefit, the TC0 and IC0 subgroup also had improved long-term OS with atezolizumab vs docetaxel. The ITT ORR was 15% in both atezolizumab and docetaxel arms, but the median duration of response was 3 times longer with atezolizumab (22.3 months [95% CI: 11.6, 31.1] vs 7.2 months [95% CI: 5.8, 12.2] with docetaxel). Seven of the 11 docetaxel-arm 3-year survivors received subsequent non-protocol therapy with anti–PD-L1/PD-1 agents. Atezolizumab had a favorable safety profile compared with docetaxel that was consistent with previous reports.

      Conclusion:
      Atezolizumab demonstrates superior 2-year and 3-year OS benefit compared with docetaxel, and this benefit is observed across histology and PD-L1 expression subgroups (including TC0 and IC0). Atezolizumab is well tolerated, and responses are highly durable. These results are consistent with long-term OS results from OAK, presented separately.

      Table. Landmark OS in the ITT, PD-L1 expression, and histology subgroups in POPLAR
      Population (n, atezolizumab vs docetaxel) 2-year OS rate, % 3-year OS rate, %
      Atezolizumab Docetaxel P value[a] Atezolizumab Docetaxel P value[a]
      ITT (144 vs 143) 32.2% 16.6% 0.0027 18.7% 10.0% 0.0419
      PD-L1 Expression Subgroups
      TC3 or IC3 (24 vs 23) 41.7% 19.9% 0.1003 37.5% 14.9% 0.0724
      TC2/3 or IC2/3 (50 vs 55) 36.1% 13.8% 0.0082 21.2% 9.9% 0.1166
      TC1/2/3 or IC1/2/3 (93 vs 102) 36.0% 19.8% 0.0124 18.0% 11.0% 0.1759
      TC0 and IC0 (51 vs 41) 25.0% 6.8% 0.0202 20.5% 6.8% 0.0693
      Histology Subgroups
      Non-squamous (95 vs 95) 32.2% 21.1% 0.0960 23.3% 12.4% 0.0585
      Squamous (49 vs 48) 32.7% 7.8% 0.0020 9.4% 5.2% 0.4603
      [a ]For descriptive purpose only. TC3 or IC3 = PD-L1 ≥ 50% TC or 10% IC; TC2/3 or IC2/3 = PD-L1 ≥ 5% TC or IC; TC1/2/3 or IC1/2/3 = PD-L1 ≥ 1% on TC or IC; TC0 and IC0 = PD-L1 < 1% on TC and IC. NCT01903993.


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      MA 10.04 - Discussant - MA 10.01, MA 10.02, MA 10.03 (ID 10824)

      11:00 - 12:30  |  Presenting Author(s): Wan-Teck Lim

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MA 10.05 - Improved Outcome for Immune Checkpoint Inhibitors (ICI) in Patients Previously Treated with Bavituximab in the SUNRISE Trial (ID 8684)

      11:00 - 12:30  |  Presenting Author(s): Michael Boyer  |  Author(s): David R Spigel, P. Mainwaring, H. Lena, M. McCleod, G. Losonczy, R.E. Sanborn, R. Natale, M. Tang, J. Lai, N.L. Kallinteris, Joseph Shan, David E Gerber

      • Abstract
      • Presentation
      • Slides

      Background:
      Bavituximab targets exposed phosphatidylserine (PS) in the tumor microenvironment, resulting in repolarization of myeloid suppressor cells/M2 macrophages to M1, production of pro-inflammatory cytokines such as IFNγ and IL-12, dendritic cell maturation, and tumor specific cytotoxic T-cell activation. SUNRISE was a Phase III trial of docetaxel with bavituximab (D+B) or placebo (D+P) in patients with treated Stage IIIb/IV non-squamous NSCLC. Recent correlative analyses from SUNRISE suggest bavituximab is more active in PD-L1 negative, immune cold tumors and thus may complement PD-1/PD-L1 ICI.

      Method:
      This subgroup analysis included all patients who received subsequent ICI after discontinuing SUNRISE study drug. We calculated overall survival (OS) both from randomization and start of subsequent ICI.

      Result:
      Ninety-three of 597 randomized patients (16%) received ICI as next line of therapy after SUNRISE assigned treatment. Baseline characteristics were balanced between the treatment groups and consistent with the ITT population. From randomization, mOS was not reached (95% confidence interval [CI], 15.2-NA) in D+B (N=46) and 12.6 months (95% CI, 10.4-17.8) in D+P (N=47) (hazard ratio [HR], 0.46; P=0.006) (Figure). From start of ICI, mOS was not reached (95% CI, 10.2-NA) in D+B and 6.2 months (95% CI, 3.9-8.7) in D+P (HR, 0.42; P=0.002). The mPFS was 6.0 months (95% CI, 3.5-6.5) in D+B and 4.4 months (95% CI, 2.6-6.3) in D+P (HR, 1.00; P=0.991). ORR was 20% vs. 13% (Odds ratio 0.6; P=0.41) for D+B and D+P, respectively. The safety profile was similar between groups and no immune related (IR) toxicities (colitis, pneumonitis, hypothyroidism) were reported.

      Conclusion:
      Within the limits of a subgroup analysis, a significant improvement in OS was observed for patients previously treated with D+B. Furthermore, bavituximab has not been associated with IR toxicities and might serve as a useful drug in combination with ICI for the treatment of immune cold tumors. Figure 1



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      MA 10.06 - Real-World Results in Non-Squamous Non-Small Cell Lung Cancer Patients: Italian Nivolumab Expanded Access Programme (ID 9580)

      11:00 - 12:30  |  Presenting Author(s): Francesco Grossi  |  Author(s): Lucio Crinò, A. Delmonte, D. Turci, D. Signorelli, F. De Marinis, H.J. Soto Parra, Domenico Galetta, Frederico Cappuzzo, F. Sperandi, M. Tiseo, G. Puppo, F. Roila, Maria Rita Migliorino, G. Tonini, F. Cognetti, A. Santoro, D. Tassinari, A. Scoppola, D. Giannarelli, Enrico Cortesi

      • Abstract
      • Presentation
      • Slides

      Background:
      Nivolumab monotherapy has shown survival benefit in patients (pts) with different tumors, including melanoma, lung cancer, renal cell carcinoma, head and neck cancer and Hodgkin lymphoma. Controlled clinical trial setting differs from what experienced by pts and physicians in routine clinical practice. Here, we report efficacy and safety results of nivolumab in pts with non-squamous non-small cell lung cancer (Non-Sq-NSCLC) treated in the Expanded Access Programme in Italy.

      Method:
      Nivolumab was available upon physician request for pts aged ≥18 years who had relapsed after a minimum of one prior systemic treatment for stage IIIB/stage IV non-Squamous NSCLC. Nivolumab 3 mg/kg was administered intravenously every 2 weeks to a maximum of 24 months. Pts included in the analysis had received at least one dose of nivolumab and were monitored for adverse events (AE) using Common Terminology Criteria for Adverse Events.

      Result:
      Overall, 1588 pts were enrolled in the EAP across 168 Italian centers. Baseline characteristics of pts were representative of Non-Sq-NSCLC population, in the advanced disease setting. As of March 2017, median overall survival (OS) was 11 months (10.0-12.0), with a median follow-up of 7.8 months (1-21.9) and a median of 7 doses (1-46). The best overall response rate (BORR) was 18%, including 10 pts (<1%) with complete response and 280 pts (17.6%) with partial response. Stable disease has been defined for 414 pts (26.0%) and totally 274 (17.2%) patients were treated beyond progression. Response rates and survival were comparable among pts regardless age (< and ≥ 75 years), presence of brain metastasis and number of prior therapies. Overall, among 1588 pts, 1254 discontinued treatment for any reason, with only 93 (7%) pts who discontinued treatment due to adverse events, in line with what observed in previous studies.

      Conclusion:
      To date, this is the largest clinical experience with nivolumab in a real-world setting and these EAP data are in line with what reported in the registrative phase 3 clinical trial. According to these results, nivolumab seems to be an effective and safe therapy for pre-treated patients with non-squamous NCSLC, supporting its use in current clinical practice.

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      MA 10.07 - Elderly Lung Cancer Patients on Immunotherapy: Preliminary Results from the ELDERS Study (ID 9840)

      11:00 - 12:30  |  Presenting Author(s): Fabio Gomes  |  Author(s): S. Woolley, R. Califano, Y. Summers, K. Baker, K. Burns, J. Yorke, Fiona Blackhall

      • Abstract
      • Presentation
      • Slides

      Background:
      Immunotherapy is revolutionising the way many cancer types are treated. The immunosenescence and the high heterogeneity of the elderly raises questions on the benefits with such treatments and real-world data is lacking.

      Method:
      ELDERS is a prospective, observational pilot study on the use of checkpoint inhibitors in patients with advanced/metastatic non-small cell lung cancer (NSCLC) or malignant melanoma. The study was designed with 2 arms, the elderly (≥ 70 years) and the non-elderly (45-69 years) with 2 co-primary endpoints, immune-related toxicity (irAE) profile and health-related quality of life (HRQoL) through the EORTC QLQ-C30. A comorbidity score (CIRS) was applied at baseline (score 0-56) and serial geriatric assessments were performed for stratification with a screening tool (G8) and further geriatric assessment as needed. A total of 110 patients of a planned 120 have been recruited. This interim analysis is of the NSCLC cohort with a minimum of 3 months on study/follow-up.

      Result:
      32 patients were included, with 96% treated with pembrolizumab (9% first-line) and 40.6% enrolled on the elderly arm. In both arms, 45% had a tumour PD-L1 expression of ≥50%. The elderly arm had more advanced disease with 69% staged M1b vs. 42.1% in younger arm (p=0.05). 69% of patients, in both arms, were performance status 0/1 at the start of treatment. The median CIRS total score was 12 for the elderly and 7 for the younger arm. 46% of elderly patients had an abnormal geriatric screening (G8≤14), requiring further assessments. With a median follow-up of 6 months, the objective response rate (ORR) was overall 19% with a median time to response of 8 weeks. The ORR was numerically higher in the elderly with 30.8% vs. 10.5% (p=0.09). 9.4% of patients on study had a grade 3/4 irAE, with no difference between study arms. Elderly patients had a numerically higher rate of admissions, 53.8% vs. 36.8% (p=0.18). No statistically significant correlation was identified between higher comorbidity score or abnormal geriatric assessment and the incidence of irAEs. No significant negative impact on the global HRQoL was detected in either arm during treatment with immunotherapy.

      Conclusion:
      Despite the small number of patients and the limited follow-up time, there is no signal in this interim analysis to indicate that elderly patients have less benefit or higher risk of irAE compared with younger patients, despite more comorbidities and geriatric syndromes. These results help to inform clinical practice in the absence of trials dedicated to the elderly population.

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      MA 10.08 - Discussant - MA 10.05, MA 10.06, MA 10.07 (ID 10825)

      11:00 - 12:30  |  Presenting Author(s): Hidehito Horinouchi

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MA 10.09 - Increased T Follicular Helper Cell Infiltration in Lung Adenocarcinoma Tertiary Lymphoid Organs (ID 8487)

      11:00 - 12:30  |  Presenting Author(s): Erin Anne Marshall  |  Author(s): K.W. Ng, Katey S.S. Enfield, S.D. Martin, K. Milne, S.H.Y. Kung, C.E. Macaulay, W.L. Lam

      • Abstract
      • Presentation
      • Slides

      Background:
      T follicular helper cells (Tfh) are an antigen-experienced CD4+ T cell subset that have been found to play crucial roles in the development of humoral immunity. In particular, their presence in the B cell-rich germinal centre of secondary and tertiary lymphoid tissue aids in B cell maturation through selection of B cells producing high-affinity antibodies. Tfh cells have known roles in autoimmune disease and B cell malignancies; however, their role in many solid tumours, including those of the lung, remains unclear.

      Method:
      We analyzed 83 paired tumour-normal lung adenocarcinoma samples from the BC Cancer Agency (BCCA) as well as 576 unpaired samples from The Cancer Genome Atlas (TCGA). Relative immune cell content was obtained from gene expression data using a linear support vector regression deconvolution approach (CIBERSORT). Spatial positioning of B and T cells within selected tumour sections was examined through IHC. The impact of Tfh infiltration on patient survival was analyzed using a Cox Proportional Hazard model.

      Result:
      T follicular helper cells are increased in tumour tissue, accompanied by global upregulation of Tfh markers PDL1 and CXCR5 in both the BCCA and TCGA cohorts. Histological analysis revealed localization of Tfh cells within tertiary lymphoid organs, with direct contact with B cells in the follicular zone observed. Importantly, Tfh recruitment appears to be an early event in tumour development and a function of neoantigen exposure, indicative of an active anti-tumour response rather than a result of chronic inflammation of the tumour microenvironment.

      Conclusion:
      T follicular helper cells are required for B cell maturation and subsequent antibody responses. As such, it is not surprising that Tfh infiltration in tumour-resident ectopic lymphoid structures correlates with patient survival in various cancer types. Given the importance of tumour-specific antibody responses in natural and therapeutic immunity, further investigation of Tfhs may show prognostic utility and be a marker of early-stage lung tumours.​

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      MA 10.10 - Tumor Draining Lymph Node Immunophenotype Corresponds with Primary Tumor Characteristics in Patients with Non-Small Cell Lung Cancer (ID 10343)

      11:00 - 12:30  |  Presenting Author(s): Daniel H. Sterman  |  Author(s): V. Murthy, J.J. Tsay, J. Minehart, K. Mangalick, J.L. Bessich, G.C. Michaud, M.A. Curotto De Lafaille, Kwok-Kin Wong, C. Goparaju, Harvey I Pass

      • Abstract
      • Presentation
      • Slides

      Background:
      There is growing appreciation for the role of tumor-draining lymph nodes (TDLN) in the dynamic of immunoediting orchestrated by non-small cell lung cancers (NSCLC). By comparing T-cell subsets and gene expression in TDLN and non-draining lymph nodes (NDLN), we aim to determine whether there is tumor-regional variation in immunophenotype.

      Method:
      Patients undergoing endobronchial ultrasound-guided transbronchial needle aspiration for the diagnosis/staging of NSCLC were recruited. Aspirates were obtained from TDLN (N1/N2 nodes with increased fluorodeoxyglucose-F-18 (FDG) avidity and/or enlarged >1cm) and NDLN (non-enlarged/non-FDG-avid N2/N3 nodes) along with peripheral blood. Samples were stained with fluorophore-conjugated antibodies (CD4-FITC, CD8-V450, CD25-PECy7, CD127-APCR700, CD45RO-PECF594) and analyzed by flow cytometry. CD4+CD25- and CD8+ effector T-cells (Teff) were sorted. Gene expression profiling was performed on sorted Teff using the Nanostring™ platform to measure differential expression between TDLN and NDLNs.

      Result:
      We compared T-cell subpopulations in TDLN and paired NDLN from 16 subjects. There were significantly fewer CD4+ T-cells in TDLN vs NDLN (10.1% vs 28.9%, p=0.0039), with more Tregs (12.1% vs 7.3%, p=0.1563) suggesting a pattern of tumor-regional immunosuppression in the TDLN. This was more consistent when tumor histology was adenocarcinoma compared to squamous cell cancer with respect to both depletion of Teff and higher proportion of Tregs (Figure 1). A more immunosuppressive TDLN phenotype was also observed with high tumor PD-L1 expression (>50%), with 36% fewer CD4+ T-cells in TDLN relative to paired NDLN when PD-L1 expression was high relative to just 3.2% fewer CD4+ T-cells with low PD-L1 expression. Gene expression in Teff has preliminarily demonstrated upregulation of genes mediating T-cell exhaustion (CTLA-4, PD-1, TGF-β) and downregulation of co-stimulatory/recruitment factors (CD28, ICOS, ICAM2) in TDLN suggesting impaired activation of tumor-regional Teff. Figure 1



      Conclusion:
      Our findings suggest that TDLNs in patients with NSCLC display a tolerogenic phenotype, with more marked immunosuppression in the setting of adenocarcinoma and high tumor PD-L1 expression.

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      MA 10.11 - Hyperprogressive Disease (HPD) Is Frequent in Non-Small Cell Lung Cancer (NSCLC) Patients (Pts) Treated with Anti PD1/PD-L1 Agents (IO) (ID 10222)

      11:00 - 12:30  |  Presenting Author(s): Roberto Ferrara  |  Author(s): C. Caramella, M. Texier, C. Audigier-Valette, L. Tessonnier, Laura Mezquita, J. Lahmar, Julien Mazieres, G. Zalcman, S. Brosseau, Virginie Westeel, S. Le Moulec, L. Leroy, B. Duchemann, C. Lefebvre, R. Veillon, S. Champiat, C. Fertè, David Planchard, Marie-Eve Boucher, G. Martinez-Bernal, E. Bria, G. Tortora, J. Soria, Benjamin Besse

      • Abstract
      • Presentation
      • Slides

      Background:
      Using Tumor Growth Rate (TGR), HPD was identified in 9% of 131 advanced cancer pts, treated with IO in a single institution (Champiat et al. 2017). In this study, we explored HPD in a large, multicenter cohort of advanced NSCLC pts treated with IO.

      Method:
      We performed a retrospective analysis of consecutive NSCLC pts treated with IO, in 8 institutions, between November 2012 and April 2017. Eligibility criteria required, for each patient: 2 CT scans performed before starting IO and one during IO, an interval between two CT scans ≥2 weeks or 3 months (m) and presence of target lesions. CT scans were centrally assessed according to RECIST 1.1 criteria. We calculated TGR before IO (TGR pre-IO) and during IO (TGR IO); patients were defined HPD if they had progression disease (PD) at first evaluation during IO and a ≥ 2-fold increase in the TGR IO compared to TGR pre-IO. Median overall survival (mOS) was estimated using Kaplan-Meier method for the total population and HPD pts.

      Result:
      Among 419 eligible pts, 86 were excluded for inadequate intervals between CT scans. Among 333 evaluable pts, 63% were male, 46% ≥65 years, 43% smokers; 12% had PS ≥ 2, 65% adenocarcinoma, 45% ≥3 metastatic sites, 22% KRAS mutation, 4% EGFR mutation, 1% ALK rearrangement; 21% had PD-L1 positive status, 10% negative, 69% unknown, >90% received single agent PD-1 inhibitor in ≥ 2 line. Response rate (RR) to IO was 18%, median follow up was 12 m [10-14]. 33% of pts had TGR IO ≥1 (not regressing tumors), 25% had TGR IO ≥ 2-fold TGR pre-IO and 54 pts (16%) had HPD. 15 pts (4%) had confirmed pseudoprogression, 3 were initially qualified as HPD. Compared to not-HPD, HPD pts had more frequently ≥ 3 metastatic sites at baseline (59% vs 43% p=0,02) and more new lung lesions during IO (34% vs 17% p=0,007). PD-L1 negative status was more common among HPD pts but the association was borderline significant (53% vs 28% p=0,05). Age, clinical, molecular characteristics, RR to treatment before IO, baseline tumor burden, liver or brain new lesions during IO were not different according to HPD status. mOS was 13 m [10-17] in the total population, 5 m [3-8] in HPD pts.

      Conclusion:
      HPD occurred in 16% of advanced NSCLC pts treated with IO and was associated with plurimetastatic disease and appearance of new lung lesions. Further work is needed to characterize HPD prognostic value.

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      MA 10.12 - Discussant - MA 10.09, MA 10.10, MA 10.11 (ID 10826)

      11:00 - 12:30  |  Presenting Author(s): David E Gerber

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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