Browsing Over 443 Presentations
170P - Advanced non-small cell lung cancer patients with low tumor mutation burden might derive benefit from anti-programmed cell death (PD)-1 and anti-programmed deathligand 1 (PD-L1) blockade
- W. Nie (Shanghai, China)
- W. Nie (Shanghai, China)
- M. Xu (Shanghai, China)
- L. Gan (Shanghai, China)
- Y. Zhang (Chongqing, China)
- B. Han (Shanghai, China)
Abstract
Background
We aimed to investigate the association between tumor mutation burden (TMB) and survival in non-small cell lung cancer (NSCLC) patients with anti–programmed cell death (PD)-1 and anti--programmed cell deathligand 1 (PD-L1) blockade.
Methods
Five retrospective cohorts using PD1/PDL1 blockades and The Cancer Genome Atlas (TCGA) lung cancer data set were included in this study. The restricted cubic spline (RCS) analysis was used to explore the association between TMB and survival. The cut-off values for TMB were determined by X-tile software. Primary outcomes were overall survival (OS) and progression-free survival (PFS). The associations between TMB and intratumor heterogeneity, number of segments, fraction of genome alterations, aneuploidy score, and T cell populations were also investigated.
Results
TMB showed an inverted J-shaped curve with survival risk in RCS plot. Two cut-off values were determined by X-tile software in each cohort. In addition to high TMB, low TMB was an independent prognostic indicator for OS and PFS in NSCLC patients treated with PD1/PDL1 blockades. Objective response rate (ORR), disease control rate (DCR), and 1-year OS rate in the low TMB group were higher than that in the medium TMB group. In TCGA lung cancer data set, low TMB was also associated with longer OS in comparison with medium TMB. Furthermore, NSCLC patients with low TMB had significantly lower intratumor heterogeneity, number of segments, fraction of genome alterations, aneuploidy score, T helper type 2 (Th2) cells, and CD8+ T cells, but higher levels of Th1 and Th17 cells.
Conclusions
NSCLC patients with low TMB might benefit from anti-PD1/PDL1 immunotherapy.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
93P - Heterogeneity score in inoperable stage III non-small cell lung cancer patients treated with definitive chemoradiotherapy: A single centre analysis
- J. Taugner (München, Germany)
- J. Taugner (München, Germany)
- L. Käsmann (Munich, Germany)
- C. Eze (Munich, Germany)
- M. Dantes (Munich, Germany)
- O. Roengvoraphoj (Munich, Germany)
- K. Gennen (Munich, Germany)
- M. Karin (Munich, Germany)
- A. Tufman (Munich, Germany)
- C. Belka (Munich, Germany)
- F. Manapov (Munich, Germany)
Abstract
Background
Inoperable stage-III non-small cell lung cancer (NSCLC) represents a very heterogeneous disease in terms of patient and tumor characteristics. A simple heterogeneity score may help to personlize multimodal therapy.
Methods
The data of 99 patients with performance status ECOG 0-1 treated with chemoradiotherapy (CRT) for inoperable stage III NSCLC, treated between 2011 and 2016 at our hospital were analyzed. Patient- and tumor-related factors were evaluated, and factors showing a significant negative association with patient survival were scored with one point each. Three subgroups with a low, intermediate and high-risk (0-1, 2-3 and 4-5 points) score were defined. The results were validated in a prospective cohort of 35 patients.
Results
Concurrent CRT was administered in 78% (n = 78) of patients and sequential CRT in 11% (n = 11), 10 Patients were treated with radiotherapy alone. 53% (n = 53) of patients received induction chemotherapy. Median overall survival (mOS) for the entire cohort was 20.8 months. Age (p = 0.020), gender (p = 0.007), cumulative tobacco pack years (PY) (p = 0.015), tumor-associated atelectasis (p = 0.004) and histology (p = 0.011) had a significant impact on survival in univariate analysis. 12, 59 and 28 patients had low, intermediate and high-risk score. MS, 1-, 2- and 3-year survival rates were as follows: not reached, 100%, 83% and 67% in the low, 22.9 months, 80%, 47% and 24% in the intermediate and 13.7 months, 57%, 25% and 18% in the high-risk score subgroup. Prospective validation of the score demonstrated one-year survival of 100% for patients in the low-risk subgroup, 93% in the intermediate-risk subgroup, and 69% in the high-risk subgroup (p = 0.100).
Conclusions
This simple heterogeneity score was developed for inoperable stage III NSCLC patients with good performance status receiving multimodal therapy. The score may aid physicians to infer clinical outcomes and optimize decisions concerning treatment strategies, as well as planning of prospective studies.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
116O - Health-related quality of life (HRQoL) of non-small cell lung cancer (NSCLC) patients treated with nivolumab in real-life: The EVIDENS study
- M. Pérol (Lyon, CEDEX, France)
- M. Pérol (Lyon, CEDEX, France)
- A. Dixmier (Orleans, France)
- F. Barlesi (Marseille, CEDEX 20, France)
- D. Debieuvre (Mulhouse, France)
- C. Raspaud (Toulouse, France)
- J. Auliac (Mantes La Jolie, France)
- N. Benoit (Amiens, France)
- P. Bombaron (Lyon, CEDEX 8, France)
- D. Moro-Sibilot (Grenoble, France)
- B. Asselain (Paris, France)
- F. Cotté (Rueil-Malmaison, France)
- P. Lamoureux (Vandoeuvre les Nancy, France)
- N. Karam (Rueil-Malmaison, France)
- N. Ozan (Rueil-Malmaison, France)
- C. Calvet (Rueil-Malmaison, France)
- B. Bryan (Uxbridge, United Kingdom)
- V. Allan (Uxbridge, United Kingdom)
- C. Audigier Valette (Toulon, CEDEX, France)
Abstract
Background
EVIDENS is an observational, prospective, multicenter cohort study following lung cancer patients initially treated with nivolumab between Oct 2016 and Nov 2017 in 146 French centers. Interim efficacy and safety results were consistent with those from nivolumab clinical trials. This analysis describes temporal changes in HRQoL.
Methods
HRQoL was measured using the EQ-5D-3L, a 3-level version consisting of the 5 dimensions descriptive system (EQ-5D) and the visual analogue scale (VAS; 0–100 [worst–best health]). Outcomes for each dimension were described as the proportion of patients with no change, improvement or deterioration, and the utility index and VAS mean changes from baseline (minimally important difference [MID] = 0.08 and ±7 point change, respectively).
Results
Overall 1,394 NSCLC patients were followed-up for a median of 11.5 months. Baseline characteristics: median age 66.0 years, 69.2% men, 89.6% current/former smokers, 83.2% PS 0-1, 31.1% squamous (SQ) histology. Baseline completion rates for EQ-5D-3L/VAS were 80.2%/77.0%. At 9 and 12 months (276 and 78 patients at risk, respectively), they were 51.4%/48.9% and 69.2%/66.7%, respectively. The table summarizes HRQoL outcomes. Of note, mean change of VAS from baseline was statistically significant at 9 and 12 months regardless of histology and MID was achieved at 12 months for SQ (+7.6 [2.1 ; 13.1]).
Conclusions
Twelve months after initiating nivolumab, all the 5 dimensions measured by EQ-5D-3L were stable in at least half of NSCLC patients and a clinically meaningful improvement of VAS was observed in the SQ patients.
Clinical trial identification
NCT03382496.
Legal entity responsible for the study
Bristol-Myers Squibb.
Funding
Bristol-Myers Squibb.
Disclosure
M. Pérol: Boards: Roche, Genentech, Eli Lilly, Pfizer, Boehringer Ingelheim, Clovis Onco, MSD, BMS, Novartis, Pierre Fabre, Takeda, AZ; Symposia: Eli Lilly, Roche, Pfizer, Amgen, Boehringer Ingelheim, BMS, Takeda, AstraZeneca. A. Dixmier: Advisory board: BMS, Roche, Novartis; Support for congress participation: BMS, Roche, AstraZeneca, Boehringer Ingelheim, MSD, Amgen, Lilly. F. Barlesi: Fees: AstraZeneca, BMS, Boehringer Ingelheim, Clovis Oncology, Eli Lilly Oncology, F. Hoffmann-La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer, Takeda. D. Debieuvre: Consulting: Roche; Honoraria as speaker: AstraZeneca, Chugai, Lilly, Roche, Novartis, Pfizer, MSD, BMS; Grant for research: Roche, AstraZeneca, BMS, Boehringer Ingelheim, Chiesi, Chugai, Janssen, Pfizer, MSD, Novartis, GSK, Sandoz; Advisory boards : Roche, Boehringer Ingelheim, Pfizer, MSD, BMS, Novartis; Support for congress participation: Roche, Boehringer Ingelheim, Novartis, Pierre Fabre, Pfizer, Mundipharma, BMS. C. Raspaud: Fees: Novartis, Boehringer Ingelheim, GSK, Chiesi, BMS, MSD, AstraZeneca, SOSO2, AgirAdom, Lilly. J.B. Auliac: Advisory boards: AstraZeneca, Boehringer Ingelheim, BMS, Roche; Speakers bureau: AstraZeneca, Amgen, BMS, Roche, Lilly, Pfizer, MSD. N. Benoit : Fees: BMS, AstraZeneca. P. Bombaron: Fees: BMS, Novartis, Boehringer Ingelheim, Roche, Amgen. D. Moro-Sibilot: Fees: BMS, MSD, Roche, AstraZeneca, Pfizer, Lilly. B. Asselain: Speakers bureau: BMS. F-E. Cotté, P. Lamoureux, N. Karam, N. Ozan, C. Calvet, B. Bryan, V. Allan: Employee: BMS. C. Audigier Valette: Principal investigator : AstraZeneca, Boehringer Ingelheim, BMS, Novartis, Roche, MSD, Pfizer; Consulting: AstraZeneca, Boehringer Ingelheim, BMS, Lilly, Novartis, MSD, Pfizer, Roche AbbVie; Speaker: AstraZeneca, Boehringer Ingelheim, BMS, Lilly, Novartis, Pfizer, Roche, MSD, AbbVie.
Q&A
Clinical practice today and future considerations
- S. Peters (Lausanne, Switzerland)
- M. Reck (Grosshansdorf, Germany)
- S. Peters (Lausanne, Switzerland)
- M. Reck (Grosshansdorf, Germany)
57P - Non-small cell lung carcinoma (NSCLC) patients with baseline brain imaging: A prospective observational study
- G. NARESH (NEW DELHI, India)
- G. NARESH (NEW DELHI, India)
- P. Malik (New Delhi, India)
- S. Khurana (New Delhi, India)
- S. Pathy (New Delhi, India)
- M. Yadav (New Delhi, India)
- D. Jain (New Delhi, India)
- H. Kancharla (New Delhi, India)
Abstract
Background
Brain metastases in NSCLC patients is the major cause of the poor survival and quality of life. Symptomatic brain metastasis at baseline are present in 5-10% of NSCLC and over the time course about 40% patients develop brain metastasis. Screening for asymptomatic brain metastasis in advanced NSCLC is controversial. Here we present our initial experience of mandatory brain imaging of all NSCLC patients irrespective of CNS symptoms and stage.
Methods
It is a prospective observation study of NSCLC patients with mandatory baseline brain imaging. Data was analysed for patients enrolled in the study from Jan 2018- Nov 2018. All patients with histology proven NSCLC were incuded irrespective of stage. Brain imaging was performed by CECT. A comprehensive CNS examination was performed at diagnosis. All statistical analysis was done by STATA version 13.Univariate analysis was done by Cox regression model.
Results
There were 238 patients enrolled. Median age was 58yrs (range 26-83yrs) with male predominance (n = 183 , 76.9%). Smokers were 65.1% ( n = 153) and majority had ECOG PS 1&2 (82%). Most common histology was adenocarcinoma - 64.6% (n = 151) . EGFR mutation could be tested in 98 of adenocarcinoma patients and was positive in 32 (32.6%). ALK (IHC-D5F3) was tested in 78 patients and was positive in 11 (14.1%) . Majority patients had stage 4 disease, 74.8% (n = 176). There was upstaging to stage 4 after brain imaging in 8% (n = 20) patients. Brain metastases was present in 22.7% (n = 54) of which 52% (n = 28) were asymptomatic. Majority had solitary lesion - 48% (n = 26), predominatly located supratentorially - 66% (n = 36). Majority of these patients received chemotherapy - 46.2% (n = 25), TKI -27.7% (n = 15), WBRT -14.8%(n = 8), BSC -22.2% (n = 12). Univariate analyses was done for age, sex, histological subtype, EGFR and ALK status, out of which younger age (<40 yrs) and adenocarcinoma histology were found to be significant predictors for presence brain metastases.
Conclusions
Brain metastasis with mandatory baseline brain imaging (atleast CECT) were found in 22.7% patients in our study and resulted in upstaging of disease in 8%. Frequency of brain metastasis were significantly higher in adenocarcinoma histology and younger age (<40 yrs).
Legal entity responsible for the study
All India Institute of Medical Sciences.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Intraoperative lymph node dissection in early stage lung cancer: Update on prognostic implications
- D. Lardinois (Basel, Switzerland)
- D. Lardinois (Basel, Switzerland)
Emerging data on TRK inhibition in TRK fusion lung cancer
- A. Drilon (New York, NY, United States of America)
- A. Drilon (New York, NY, United States of America)
146P - Clinical significance of ROS1 5’ deletions detected by FISH and response to crizotinib
- F. Dall'Olio (Bologna, Italy)
- F. Dall'Olio (Bologna, Italy)
- G. Lamberti (Bologna, Italy)
- E. Capizzi (Bologna, Italy)
- E. Gruppioni (Bologna, Italy)
- F. Sperandi (Bologna, Italy)
- A. Altimari (Bologna, Italy)
- F. Giunchi (Bologna, Italy)
- M. Fiorentino (Bologna, Italy)
- A. Ardizzoni (Bologna, Italy)
Abstract
Background
ROS1-rearranged non-small cell lung cancer (NSCLC) patients (pts) are eligible for crizotinib therapy. Diagnosis is based on break-apart fluorescence in situ hybridization (FISH), as for ALKrearrangements, and include 5’ deletions. We report assessment of ROS15’ deletion by FISH and next-generation sequencing (NGS) and outcome of crizotinib treatment.
Methods
We included all consecutive NSCLC pts treated at our Institution with: i) diagnosis of 5’ ROS1 gene fusion by break-apart FISH (≥15% of tumor cells with any 5’ deletion pattern); ii) availability in the samples of at least 50 ng of extracted RNA with at least 50% tumor cell enrichment; iii) treatment with crizotinib for at least 4 weeks following the diagnosis of ROS1fusion; iv) availability of clinical and radiological response data after therapy. FISH assay was performed using the Zytolight SPEC ROS1 Dual Color Break Apart Probe (ZytoVision, Germany). NGS was performed on Ion Torrent Personal Genome Machine (Thermo Fisher Scientific). The RNA panel identified rearrangements in 23 genes including ROS1 rearrangements with EZR, CD74 and SCD4.
Results
Eight patients were included. No patient had brain metastasis at diagnosis. Five pts were never-smoker, 2 light former smoker and 1 (case #1) a current heavy smoker (50 pack-year). Crizotinib therapy lasted for a mean of 11.0 months (range 2-31). The median overall survival was not reached at a median follow-up of 11.1 months (15.7 months for censored only). In 4 of the 8 cases (cases #2, 3, 7, 8; 50%), NGS confirmed a ROS1 fusion: 3 of them with the partner EZR and 1 with SCD4. All of these pts showed an objective response to crizotinib, 2 of them being complete responses according to RECIST v1.1 criteria. All these pts were alive at the time of last follow-up. In the other 4 pts (cases # 1, 4 ,5 ,6), NGS analysis did not detect ROS1 fusions. Of these, objective response to crizotinib was observed in only 2 pts, including one (case #5) with a concomitant EML4-ALKrearrangement, confirmed by FISH. The two other patients experienced rapid progressive disease.
Conclusions
FISH-detected ROS15’ deletion is associated with a high response probability to crizotinib, similarly to classical ROS1 gene rearrangement. However, confirmation with at least one other method, e.g. NGS, is recommended, in order to exclude possible false positive results.
Legal entity responsible for the study
The authors.
Funding
This work was in part supported by the Pallotti fund to Michelangelo Fiorentino.
Disclosure
All authors have declared no conflicts of interest.
How can ESMO help to implement personalised treatment in clinical practice
- R. Stahel (Zurich, Switzerland)
- R. Stahel (Zurich, Switzerland)
Panel discussion
- M. Garassino (Milan, Italy)
- N. Reinmuth (Gauting, Germany)
- M. Garassino (Milan, Italy)
- N. Reinmuth (Gauting, Germany)
192P - Characterization and potential role of PD-L1 positive lung cancer stem cells in lymph nodes metastasis
- A. Raniszewska (Warsaw, Poland)
- A. Raniszewska (Warsaw, Poland)
- E. Rutkowska (Warsaw, Poland)
- R. Sokolowski (Warsaw, Poland)
- J. Domagala-Kulawik (Warsaw, Poland)
Abstract
Background
An immunotherapy was found to be effective in achieving long-term survival in some lung cancer patients and has emerged to searching for new immune biomarkers. It is suggested that lung cancer stem cells (LCSCs) are responsible for tumor initiation, maintenance and its metastatic potential. In our previous studies, we confirmed the presence of PD-L1 positive LCSCs (EPCAM+/CD133+) in metastatic lymph nodes (LNs). The aim of this study was to assess the presence of LCSCs in LNs aspirates using extended LCSCs markers and compare it with clinical data of patients.
Methods
LCSCs were analyzed in LNs aspirates obtained during EBUS TBNA procedure. Flow cytometry with anti-CD44, anti-CXCR4 antibodies was applied to identify LCSCs. Additionally anti-PD-L1 was applied and geometric mean fluorescence (GMF) intensity of PD-L1 on LCSCs was measured.
Results
20 patients with confirmed non small cell lung cancer were enrolled. The highest proportion of PD-L1+ LCSCs was found in patients with metastatic disease; median values (p25-75)- 4,76% (1,51-7,65%) versus non metastatic- 0.01% (0-0,13%), p < 0.05. Higher percentage of PD-L1 positive LCSCs was found in patients with EGFR mutations and ALK rearrangements than in those without oncogenic addiction, p < 0.05. We observed significant correlation between proportion of PD-L1+ LCSCs and pack years smoked (r = 0.76, p < 0.05) and between expression (GMF) of PD-L1 and pack years smoked (r = 0.67, p < 0.05).
Conclusions
We confirmed the significance of LCSCs in tumor growth and aggressiveness. LCSCs may serve as a potential strategy to enhance cancer immunotherapy efficacy. The development of predictive biomarkers is needed to optimize patient benefit and guide combination approaches.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.