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D. Planchard
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MA09 - Immunotherapy Combinations (ID 390)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:M. Sebastian, E.B. Garon
- Coordinates: 12/06/2016, 14:20 - 15:50, Strauss 2
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MA09.04 - Discussant for MA09.01, MA09.02, MA09.03 (ID 6991)
14:38 - 14:50 | Author(s): D. Planchard
- Abstract
- Presentation
Abstract not provided
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MA11 - Novel Approaches in SCLC and Neuroendocrine Tumors (ID 391)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:P. Lara, A. Mohn-Staudner
- Coordinates: 12/06/2016, 14:20 - 15:50, Strauss 3
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MA11.02 - Mutational Burden in Pulmonary Neuroendocrine Tumors (puNETs) (ID 6099)
14:26 - 14:32 | Author(s): D. Planchard
- Abstract
- Presentation
Background:
Tumor mutational load (TML) by whole-exome sequencing (WES) is a potential determinant of response to immune checkpoint blockers. The use of PD-L1 as a predictive biomarker for use of PD-1/PD-L1 inhibitors is limited. To date, there are few data concerning TML in puNETs.
Methods:
WES was performed in fresh-frozen tumor-normal pairs from 35 typical carcinoid (TC), 4 atypical carcinoid (AC) and 9 large-cell neuroendocrine carcinoma (LCNEC) consecutively collected. Exome enriched libraries were sequenced on an Illumina HiSeq 2000 with a paired-end 2 x 100 bp protocol. Reads were aligned to the reference hg19 using an implementation of the Burrows-Wheeler Aligner, and a BAM file was produced for each tumor and normal sample using the Picard pipeline. The MuTect algorithm was used to identify SSNVs in WES data. We used a minimal allelic fraction cutoff of 0.1. Patients' characteristics and TML were described (median and interquartile for quantitative variables and frequencies for qualitative variables). To evaluate the effect of some factors on the TML, an analysis of variance was used. A log transformation was performed according to the distribution of the TML. The median follow-up was estimated using the Schemper's method. The number of relapses and deaths was reported.
Results:
Cohort included 24 male and 24 female. Median age at diagnosis was 57 [Q1= 46; Q3= 70] years, 38% of carcinoids (TC+AC) and 89% of LCNEC were smokers, 26 (54%) stage I, 16 (34%) stage II, 3 (6%) stage III and 3 (6%) stage IV. All patients underwent surgery and 5 (10%) received neoadjuvant treatment. Median follow-up was 32.6 (min= 4.4; max= 179.9) months; there were 8 (17%) relapses (6/9 LCNEC, 2/39 carcinoids) and 10 deaths. On average, 11.6 Gb of sequence were produced per sample, aiming a mean coverage of 72X. Overall median TML was 0.31/Mb [Q1= 0.22; Q3= 0.67], significantly lower in carcinoids tumors than LCNEC (0.28 [Q1= 0.20; Q3= 0.38]/Mb vs. 2.98 [Q1= 1.20; Q3= 4.84]/Mb, respectively, p<0.0001). Similar findings were observed among smoker vs. non-smoker patients (0.28 [Q1= 0.18; Q3= 0.38]/Mb vs. 0.60 [Q1= 0.28; Q3= 2.98]/Mb, respectively, p=0.04). Both variables were found to be independently correlated with TML within the ANOVA test (p=0.0016).
Conclusion:
Our findings provide a unique portrait of puNETs, revealing different histotype mutational burden. Continued work in harnessing immunological data in puNETs are needed for better understanding immunotherapy-treatment option in this orphan disease.
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OA22 - Novel Trials and Biomarkers in Malignant Pleural Mesothelioma (ID 403)
- Event: WCLC 2016
- Type: Oral Session
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:H. Pass, N. Van Zandwijk
- Coordinates: 12/07/2016, 14:20 - 15:50, Strauss 3
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OA22.02 - Nintedanib plus Pemetrexed/Cisplatin in Patients with MPM: Phase II Findings from the Placebo-Controlled LUME-Meso Trial (ID 4191)
14:30 - 14:40 | Author(s): D. Planchard
- Abstract
- Presentation
Background:
Standard first-line treatment for patients with unresectable malignant pleural mesothelioma (MPM) is pemetrexed/cisplatin, yielding a median overall survival (OS) of only ~1 year, thus new approaches are required. As demonstrated by the bevacizumab MAPS study, inhibition of the VEGF pathway is of interest as a treatment approach for MPM. Nintedanib is an oral, triple angiokinase inhibitor of VEGFR, PDGFR and FGFR. This study will evaluate the efficacy and safety of nintedanib plus pemetrexed/cisplatin in patients with advanced MPM.
Methods:
Patients with unresectable MPM (chemo-naïve, ECOG PS 0–1) were stratified by histology (epithelioid/biphasic) and randomised (1:1) to receive up to 6 cycles of pemetrexed (500 mg/m[2])/cisplatin (75 mg/m[2]) on Day 1 plus nintedanib (200 mg bid)/placebo on Days 2–21. Patients without disease progression received maintenance treatment with nintedanib/placebo. The primary endpoint was progression-free survival (PFS).
Results:
87 patients were randomised to receive pemetrexed/cisplatin, plus nintedanib/placebo. Patient characteristics were comparable between the groups. PFS was longer in the nintedanib vs the placebo arm, in both the overall study population and in epithelioid patients (Table 1). Preliminary OS data also favour nintedanib. All patients experienced at least one adverse event (AE, any grade), with 7% of patients in the nintedanib arm discontinuing due to AEs, vs 15% with placebo. Serious AEs occurred in 36% vs 42% of patients in the nintedanib and placebo arms, respectively. The most common ≥grade 3 AEs occurring in nintedanib vs placebo patients were neutropenia (34% vs 10%), ALT increase (14% vs 2%) and gamma glutamyltransferase increase (14% vs 0%).
Conclusion:
Nintedanib plus pemetrexed/cisplatin demonstrated clinical efficacy with improved PFS and a tolerable safety profile in patients with unresectable MPM. Based on these promising findings, this Phase II study was extended to a confirmatory Phase III trial, which is currently enrolling patients. Clinical trial identifier: NCT01907100.
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P1.07 - Poster Session with Presenters Present (ID 459)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.07-012 - Efficacy of Immune Checkpoint Inhibitors in Large Cell Neuroendocrine Lung Cancer: Results from a French Retrospective Cohort (ID 4613)
14:30 - 14:30 | Author(s): D. Planchard
- Abstract
Background:
Nivolumab and pembrolizumab, two programmed death (PD)-1 immune-checkpoint–inhibitor antibodies, demonstrated superiority versus standard chemotherapy in second- third line in both squamous and non-squamous lung cancer. Large cell neuroendocrine lung cancer (LCNEC) is a rare tumour often treated as a small cell lung cancer, but there is not a standard of care after a first line progression. Aim of the study was to assess clinical efficacy of PD-1 inhibitors in these patients.
Methods:
We retrospectively reviewed all consecutive LCNEC stage IIIB- IV patients treated with nivolumab or pembrolizumab after platinum-based first line therapy between July 2014 and November 2015 in six French centres. Patients were followed until June 2016. The drugs were given in an early access program or a clinical trial.
Results:
The analysis included 10 patients with advanced stage disease. Eight patients (80%) had a stage IV disease with a median age of 59 [interquartile range (IQR) 55-62] years. The majority were males (n=9; 90%), with good performance status (0-1; 9/90%) and 50% were treated in third line or further. Three patients presented brain metastases. In 5 cases a molecular test was done, finding in one case (20%) a KRAS mutation. Patients received a first line treatment with platinum and etoposide in 8 cases (80%) with a disease control rate of 50%. Nine patients received nivolumab and the PD-L1 status was never performed, while the patient treated with pembrolizumab expressed PD-L1. Patients received a median number of 16 [IQR, 13-18] cycles, 6 showed a partial response (60%), 1 a stable disease (10%). Median PFS was 57 [24-57] weeks. Most of the patients stopped treatment due to disease progression (n=4; 80%), only one for a pulmonary interstitial pneumonia.
Conclusion:
Our findings suggest that the use of immune-checkpoint–inhibitors in LCNEC could be explored in a larger cohort of patients. This treatment could be considered in the scenario of a disease with limited therapeutic strategy.
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03b-050 - Prognostic Value of HLA-A2 Status in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients (ID 4773)
14:30 - 14:30 | Author(s): D. Planchard
- Abstract
Background:
The class I human leucocyte antigen (HLA) molecules play a critical role as escape mechanism of antitumoral immunity. Indeed, novel immune-targeting cancer vaccines are currently developped in HLA-A2 positive patients for modulating the T cells response. The HLA-A2 status has been proposed as prognostic factor in lung cancer, but previous evidence is inconsistent. The aim of this study is to evaluate the role of HLA-A2 status as prognostic factor in a large cohort of advanced NSCLC patients.
Methods:
Advanced NSCLC patients eligible to platinum based chemotherapy (CT) were included from Oct. 2009 to July 2015 in the prospective MSN study (IDRCB A2008-A00373-52) in our institute. HLA-A2 status was analysed by flow cytometry. Clinical and pathological data were collected in a Case Report Form (CRF). Statistical analysis was performed with software SAS version 9.3.
Results:
Five hundred forty-five advanced NSCLC patients were included. Three hundred forty-four patients (63%) were male, median age was 61 years (21-84); 466 (85%) were smokers. Four hundred seven (75%) were adenocarcinoma, 69 (13%) squamous and 69 (13%) others histologies. Among 259 patients with known molecular profile, 113 (43.6%) NSCLC were KRASmut, 50 (19.3%) EGFRmut, 30 (11.6%) ALK positive, 9 (3.5%) BRAFmut and 8 (3.1%) FGFR1amp. Four hundred forty-seven (83%) patients had performance status 0-1 at diagnosis. Five hundred eight patients (93%) were stage IV, and 37 (7%) stage IIIB. All received platinum-based CT (49% cisplatine, 42% carboplatin and 9% both). No association was observed between HLA-A2 status and patient or tumor characteristics. The median progression free survival to platinum-based CT (PFS) was 5.6 months [confidence interval (CI) 95% 5.20-6.10]. In HLA-A2 positive patients, the median PFS was 5.6 months [CI 95% 5.1-6.4] vs. 5.7 months [CI 95% 4.9-6.2] in HLA-A2 negative patients (HR 1, Wald test, p=0.8).The median overall survival (OS) was 12.6 months [CI 95% 11.3-14.3]. The median OS was 12.8 months [CI 95% 11-14.6] in HLA-A2 positive vs. 12.5 months [CI 95% 10.4- 15.3] in HLA-A2 negative patients (HR 1, Wald test p=0.61). No significant differences were found between HLA-A2 status and PFS and OS in advanced NSCLC patients.
Conclusion:
Our study has observed no prognostic role of HLA-A2 status in advanced NSCLC patients.
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P2.06 - Poster Session with Presenters Present (ID 467)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.06-005 - Phase 1 Study of Ramucirumab or Necitumumab in Combination with Osimertinib (AZD9291) in Advanced T790M-Positive EGFR-Mutant NSCLC (ID 4278)
14:30 - 14:30 | Author(s): D. Planchard
- Abstract
Background:
Despite the likelihood of an initial response to 1st or 2nd generation EGFR-TKI, EGFR mutant patients develop disease progression. The most frequent mechanism of acquired resistance is the EGFR T790M gatekeeper mutation. Novel treatment options are needed in this treatment resistant patient population. Osimertinib, a third-generation EGFR TKI targeting mutant EGFR including T790M, is an oral, irreversible, selective inhibitor. Ramucirumab and necitumumab are human IgG1 monoclonal antibodies to VEGFR-2 and EGFR, respectively. This phase 1, open-label, multicenter study with expansion cohorts (JVDL; NCT02789345) is designed to evaluate the safety and preliminary efficacy of ramucirumab or necitumumab in combination with osimertinib in patients with advanced EGFR T790M-positive NSCLC who have progressed after EGFR TKI therapy.
Methods:
This study includes patients with advanced or metastatic EGFR T790M-positive EGFR activating mutant (exon 19 deletions or L858R) NSCLC, with measurable disease and ECOG performance status 0-1 who have experienced disease progression on one prior EGFR TKI regardless of prior chemotherapy. Patients previously treated with an EGFR antibody or 3rd generation EGFR TKI for NSCLC are not eligible. In the phase 1a dose de-escalation portion (3+3 design), all patients (n=6 to 24) will be administered daily oral osimertinib (80 mg) with either an initial dose of 10 mg/kg IV ramucirumab on day 1 of every 2-week cycle or 800 mg IV necitumumab on days 1 and 8 of every 3-week cycle. One level of dose de-escalation is planned for each arm. A dose reduction (level -1) to 8 mg/kg IV ramucirumab or 600 mg IV necitumumab is planned if 2 or more patients have DLTs in either arm. After the DLT evaluation, the study will open a dose-expansion portion (phase 1b) and 25 patients in each Arm will receive study treatment until disease progression or a criterion for discontinuation is met. The primary objective is to assess safety and tolerability of ramucirumab or necitumumab in combination with osimertinib. Secondary endpoints include preliminary efficacy and pharmacokinetics. An exploratory biomarker objective includes the assessment of correlations between EGFR-mutations in tissue and serial blood samples with clinical outcomes. Primary analyses will be conducted approximately 6 months after the last patient receives initial dose.
Results:
Section not applicable
Conclusion:
Section not applicable
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-102 - Osimertinib Benefit in ctDNA T790M Positive, EGFR-Mutant NSCLC Patients (ID 5472)
14:30 - 14:30 | Author(s): D. Planchard
- Abstract
Background:
The third generation tyrosine kinase inhibitors (TKIs) osimertinib is approved for patients with acquired epidermal growth factor receptor (EGFR) T790M mutations in advanced non-small cell lung cancer (NSCLC) patients. New tissue biopsy to detect T790M cannot always be performed, due to the size or location of the lesions and risk of complications to the patient. As an alternative, liquid biopsies based on circulating cell-free tumor DNA (ctDNA) analysis have been described. We assess the efficacy of osimertinib in ctDNA T790M-positive, EGFR-mutant NSCLC patients with progression under first- or second-generation EGFR TKIs ineligible for tissue biopsy at progression; and the feasibility of identifying T790M mutations in ctDNA isolated from blood samples in this cohort of patients.
Methods:
ctDNA analysis using enhanced eTAm-Seq™ assay (Inivata), and enhanced version of the Tam-Seq ® assay was conducted in 48 eligible patients treated in a single center between April 2015 and April 2016. Patients determined to have T790M mutation were prescribed osimertinib (80mg daily). Objective response rate (ORR) by RECIST 1.1 criteria was centrally reviewed and correlated with (A) T790M allele fraction, (B) EGFR activating mutation allele fraction, and (C) T790M by EGFR activating mutation allele fraction ratio.
Results:
T790M status in ctDNA was assessed in 48 EGFR-mutant NSCLC patients. Median age was 65 years (range 37-83); 36 (75%) patients were women and 58% were never-smoker. EGFR mutation status was Del19 in 33 (69%) and L858R in 15 (31%) NSCLC patients. The ctDNA T790M mutation was positive in 24 out of 48 (50%) patients, and 23 out of 24 T790M-positive samples maintained the original activating EGFR mutation in ctDNA analysis. Among evaluable patients (n=16), osimertinib gave a partial response rate of 62.5% and a stable disease rate of 37.5%. Neither correlation between ctDNA T790M AF and RECIST radiological response was observed, nor with the other parameters evaluated. Of the seven cases with best response (decrease of 50% or more in size), 3 cases had T790M detected at <0.25%.
Conclusion:
Osimertinib efficacy in a real-world setting among T790M-positive tumours detected in ctDNA from liquid biopsy support the use of such liquid biopsies as a surrogate marker for T790M in tumour tissue, avoiding the need for invasive tumor biopsies for personalising treatment in lung cancer patients
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P3.02c - Poster Session with Presenters Present (ID 472)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 4
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02c-031 - Immune Checkpoint Inhibitors (IC) and Paradoxical Progressive Disease (PPD) in a Subset of Non-Small Cell Lung Cancer (NSCLC) Patients (ID 5448)
14:30 - 14:30 | Author(s): D. Planchard
- Abstract
Background:
In non-squamous NSCLC PD-L1 negative patients (pts), IC might increase the risk of early death compared to docetaxel in the phase III study Checkmate 057. Tumor Growth Rate (TGR) is calculated using 2 CTscans and the time interval between the 2 exams. It integrates tumor dynamics and kinetics. We hypothesized that TGR could identify a subset of pts named PPD, in which IC could accelerate tumor progression, leading to early death.
Methods:
We performed a retrospective case study of all NSCLC pts treated by IC in a single institution between Dec. 12 and Feb. 16. CT scan were centrally reviewed by a senior radiologist and assessed according to RECIST 1.1 criteria. We calculated TGR at baseline of IC (baseline CTscan (n) vs n-1 CTscan) and TGR during IC (n+2 CTscan vs n+1 CTscan). We further estimated the difference (deltaTGR) between TGR during IC and TGR at baseline. DeltaTGR>0 means IC speeds up tumor growth. PPD was defined as deltaTGR>50%, corresponding to an absolute increase in TGR greater than 50% per month. PDL1 expression was assessed with the SP142 clone.
Results:
89 pts were eligible. 58% were male, median age 60 (41-78); 15% never smokers. 62 pts had adenocarcinoma, 21 squamous and 6 other histologies. Mutational status was unknown for 14 pts; 36% wild type, 9 pts EGFRmut, 25 pts KRASmut. PDL1 expression was positive in 25 pts, unknown in 57 pts. 52 pts (58%) received nivolumab, 25 pembrolizumab and 12 atezolizumab. Treatement was received as 1-3[rd] line in 52 pts, and as ≥ 4[th] line in 37 pts. Overall, 25 pts (28%) had a response according to RECIST 1.1 criteria, 31 (35%) a stable disease. Median OS was 14.7 months. During IC, deltaTGR was <0 in 79 pts and >0 in 20 pts. Among the 20 pts with deltaTGR>0, 9 had a PPD. Characteristics (age, sex, smoking status, pathology, number of previous line, PDL1 status) of the 9 pts were not different from other pts. None of the PPD were pseudoprogression. Median OS of PPD vs others was 3.2 and 23 months, respectively. PPD was not more frequent in tumors with high baseline TGR.
Conclusion:
Our results suggest that PPD is a new subset of response criteria in which IC may increase tumor progression, leading to a poorer survival. Rapidly growing disease at study entry nor RECIST criteria could predict the occurrence of PPD.
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P3.02c-032 - Interstitial Pneumonitis Associated with Immune Checkpoint Inhibitors Treatment in Cancer Patients (ID 5670)
14:30 - 14:30 | Author(s): D. Planchard
- Abstract
Background:
Immunotherapy is now a standard of care in melanoma, lung cancer and is spreading across other tumours. Immune checkpoint inhibitors (ICI) are generally well tolerated but can also generate immune-related adverse effects. Since the first trials, pneumonitis has been identified as a rare but potentially life-threatening event.
Methods:
We conducted a retrospective study over a period of 5 months in centers experienced in ICI use in clinical trials, access programs or following national approval. We report the main features of possibly related pneumonitis occurring in patients treated with ICI with a particular focus on clinical presentation, radiologic patterns (with a double reviewing by radiologists and pulmonologists), pathology and therapeutic strategies.
Results:
We identified 71 patients with possibly related pneumonitis including 54 NSCLC and 13 melanoma. They mainly received PD1 inhibitors. Pneumonitis usually occurred in male, former or current smokers with a median age of 59 years. We observed grade 2/3 (n= 45, 65.2%) and grade 5 (n= 6, 8.7%) pneumonitis. The median duration time between the introduction of immunotherapy and the pneumonitis was 2.2 months [0.1-27.4]. Ground glass opacitiy on lung CT-scan were the most predominant lesion 80.9% (n=55), followed by consolidations 44.1% (n=30), reticulations 36.7% (n=25) and bronchiectasis in 20.6% (n=14). When performed, bronchoalveolar lavage (BAL) showed a T-lymphocytic alveolitis and transbronchial biopsy an inflammatory and lymphocytic infiltration. Pneumonitis treatment was steroids (86.6%) and/or antibiotics (67.6%). Immunotherapy was stopped after the pneumonitis for 65 cases (92.9%) and reintroduced for 12 (9.4%) cases. Twenty-four patients (34.3%) were dead at the last follow-up and 46 patients (65.7%) were still alive. Among the living patients, the pneumonitis outcome was a total recovery in 12 patients, improvement in 22 patients, stability in 10 patients, worsening evolution in 1 patient (1 unknown). Causality of immunotherapy was evaluated by investigators as “possible” for 34 patients (49.3%), “probable” for 17 (24.6%), “certain” for 15 (21.7%) other causes for 3 (4.3%) and 2 unknowns. Median overall survival from the onset of pneumonitis was 6 months.
Conclusion:
This serie, the largest to date, of immune-related pneumonitis demonstrates that it occurs usually during the first months and displays specific radiologic features. As there is no clearly identified risk factor, oncologists should be able to detect, diagnose (with CT-scan and bronchoscopy) and treat this adverse event. An early management is usually associated with a favourable outcome and requires a close collaboration between pulmonologists, radiologists and oncologists.
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P3.02c-065 - Neutrophil-To-Lymphocyte and Other Ratios as Prognostic and Predictive Markers of Immune Checkpoint Inhibitors in Advanced NSCLC Patients (ID 4775)
14:30 - 14:30 | Author(s): D. Planchard
- Abstract
Background:
The inflammatory status in advanced cancer patients before treatment have been asocciated with poor prognosis. Recently, neutrophil-to-lymphocyte ratio (NLR), derived NLR, platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) have been proposed to mesure the inflammatory status at diagnosis. However their prognostic/predictive value for immune checkpoint inhibitors is unknown. The aim of this study is to evaluate the role of these parametres to predict outcomes to immune checkpoint inhibitors in NSCLC patients.
Methods:
We conducted a retrospective study of a cohort of advanced NSCLC patients (pts) treated with immune checkpoint inhibitors (nivolumab (nivo), pembrolizumab (pembro) or atezolizumab (atezo)) from Nov. 2013 to July 2016 in our institute. Clinical data were collected and complete blood count, lactate dehydrogenase (LDH), and albumin were also collected at baseline and at 2[nd] cycle (after 14 days in case of nivo and after 21 days for pembro and atezo) for monitoring the blood cells counts and the ratios. A statistical analysis was performed with R studio software.
Results:
65 NSCLC patients were included. Twenty-five patients (38%) were female, median age was 65 years (30-86); 55/65 patients were current/former smokers and 9 (14%) non-smokers; 50 patients (76%) had performance status 1. Forty-two (64.6%) had an adenocarcinoma, seventeen (26%) squamous cell carcinoma, three (5%) large cells, and three others histologies. Fifty-seven patients (88%) had stage IV (25% had M1a, 75% M1b), and eight (12%) locally advanced disease. The median of immunotherapy line was 2 (2-9). Seventeen patients (26%) received another line of treatment after immunotherapy. Absolut leucocyte count (WBC) and absolut neutrophil count (ANC) at immunotherapy beginning (baseline) were correlated with prognosis (p<0.0001 and p<0.0001). NLR, dNLR [ANC/(WBC-ANC)] and PLR were significantly correlated with survival from immunotherapy beginning (p<0.001, p=0.021 and p=0.003, respectively). An early increase of NLR and dNLR at 2[nd] cycle were prognostic for shorter survival (p<0.0001 and p=0.0011). Increases of ANC and absolut eosinophils count (AEC), and decreases of absolut lymphocytes count (ALC) at 2[nd] cycle were also associated with poor prognosis (p=0.002, p=0.002 and p=0.048 respectively). Lactate dehydrogenase (LDH) and albumin at baseline were significant prognostic factors to immunotherapy (p<0.0001 and p=0.001).
Conclusion:
Our preliminary results suggest that “low cost” and routine blood markers and their early changes could be associated with outcomes to immunotherapy in advanced NSCLC. A multivariate analysis on 130 patients will be presented.
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P3.02c-066 - HLA-A2 Status and Immune Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients (ID 4774)
14:30 - 14:30 | Author(s): D. Planchard
- Abstract
Background:
The class I human leucocyte antigen (HLA) molecules play a critical role in tumor recognition by T cells and the loss of expression seems to be an escape mechanism of antitumoral immunity. Novel immune-targeting cancer vaccines are currently developped in HLA-A2 positive patients for modulating the T cells immune response. We hypothesized that HLA-A2 status could influence the prognosis and response to immune checkpoints (IC) inhibitors.
Methods:
Advanced NSCLC patients treated with nivolumab or within clinical trials (with pembrolizumab or atezolizumab) were prospectively included from November 2013 to July 2016 in our institute. HLA-A2 status was analysed by flow cytometry; PDL1 was analysed by immunohistochemistry. Clinical and biological data were collected at baseline and after cycle 1. Statistical analysis was performed with R studio.
Results:
Out of 160 patients treated, HLA-A2 status was available for 65 patients. 40 patients (61.54%) were male, median age was 65 years (30-86); 55 (84.6%) were smokers and 57 (72.3%) had performance status 0-1. 42 patients (64.6%) had an adenocarcinoma, 17 (26.1%) squamous cell carcinoma and 6 (9.2%) others histologies. Molecular status was available in 55 patients: 6 (10.9%) were EGFRmut, 3 (5.4%) ALK positive, 13 (23.6%) KRASmut, 3 (5.4%) BRAFmut and 12 (21.8%) wildtype. PDL1 expression was positive in 13 patients (20%), negative in 5 (7.7%) and unknown in 47 (72.3%). The median of previous lines of treatment was 1 (1-8). HLA-A2 status was positive in 32 patients (49.23%) and negative in 33 (50.76%). HLA-A2 positivity was associated with higher number of metastases at baseline and the presence of liver metastasis (p=0.04 and p= 0.016, respectively). Other patient and tumor characteristics were well balanced between HLA-A2 + and - groups. The median progression free survival to immunotherapy (iPFS) was 4 months [0-40]. In HLA-A2 positive the median iPFS was 4 months vs 4 months in HLA-A2 negative (p=0.63). The median overall survival (OS) was 21 months [0-121]. The median OS was 18.5 months in HLA positive vs. 24 months in HLA-A2 negative patients (p=0.25). No significant difference between both HLA-A2 groups was identified.
Conclusion:
Our preliminary results suggest that HLA-A2 status has no predictive or prognostic value in NSCLC patients treated with immune checkpoint inhibitors. An updated analysis on 78 patients will be presented.
