86O The effect of prophylactic cranial irradiation (PCI) for young stage III NSCLC patients: Subgroup analyses of the NVALT-11/DLCRG-02 study W.J.A. Witlox1 , B. Ramaekers1 , H.J.M. Groen2 , A-M.C. Dingemans3 , J. Praag4 , J. Belderbos5
, V. Van der Noort6
, H. Van Tinteren6
, M.A. Joore1
, D. De Ruysscher7 1
Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center (MUMC), Maastricht, Netherlands,2
University Hospital Groningen (UMCG), Groningen, Netherlands,3
Pulmonology, Maastricht University Medical Center (MUMC), Maastricht, Netherlands,4
Department of Radiation Oncology, Erasmus University Medical Center, Rotterdam, Netherlands,5
The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands,6
Department of Biometrics, Het Nederlands Kanker Instituut Antoni van Leeuwenhoek (NKI-AVL), Amsterdam, Netherlands,7
Radiation Oncology (Maastro Clinic), Maastricht University Medical Centre (MUMC)-MAASTRO Clinic, Maastricht, Netherlands
Background:The NVALT-11/DLCRG-02 phase III study compared PCI to observation after chemo-radiotherapy (RT) for stage III NSCLC and showed a significant decrease in the cumulative incidence of symptomatic brain metastases (BM) in the PCI arm at two years (7% vs 27% [HR 0.23]). We here performed exploratory subgroup analyses. Methods:Two year cumulative incidence rates were calculated and competing risk regression, with death of any cause as competing risk, was used to examine the time to symptomatic BM in the following subgroups: age, gender, performance status, disease stage and tumour type, prior surgery, chemotherapy cycles, thoracic RT dose and total concurrent chemo-RT treatment time. For continuous variables, the median was used as a cut-off value. The effect of PCI was only examined if the initial result was significant.
Results:In total, 174 patients were analysed. The symptomatic BM incidence was sig-nificantly lower in the subgroup of older (>61 years) versus younger (¼ <61 years) patients (7% vs 26% [HR 0.25]). Stratified by age, PCI only significantly reduced the symptomatic BM incidence in younger patients (9% vs 42% [HR 0.18])(Table).
Conclusions:The symptomatic BM incidence was significantly lower in older (>61 years) compared to younger (¼ <61 years) patients, likely due to higher numbers of adenocarcinoma in the younger patients group. The effect of PCI was only significant in younger patients. This study was randomized based on treatment allocation and sub-groups might be too small to detect significant differences. Therefore, our results are hypothesis generating and should be prospectively tested.
Table: 86O Time to symptomatic BM per subgroup
Subgroup Hazard ratio 95% CI
Age (>61 years vs 61 years) All 0.25 0.10 - 0.60 61 PCI vs observation 0.18 0.06 - 0.53 >61 PCI vs observation 0.47 0.09 - 2.52 Female vs Male 1.31 0.92 - 1.88
WHO performance status 0 – –
1 0.86 0.41 - 1.83
2 2.12 0.59 - 7.63
Squamous vs non-squamous 0.76 0.34 - 1.66
Stage IIIb vs IIIa 0.97 0.47 - 1.98
Prior vs no prior surgery 1.21 0.45 - 3.29 Chemotherapy cycles (>3 vs 3) 0.97 0.42 - 2.22 Thoracic RT dose (>60 Gy vs 60 Gy) 1.15 0.57 - 2.36 Total concurrent chemo-RT time
(>64 days vs 64 days)
1.43 0.70 - 2.94
Annals of Oncology
abstracts
Volume 30 | Supplement 2 | April 2019
doi:10.1093/annonc/mdz067 | ii33
Clinical trial identification:NCT01282437.
Legal entity responsible for the study:Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose (NVALT).
Funding:Has not received any funding.
Disclosure:All authors have declared no conflicts of interest.
87P Time-series of peripheral blood biomarkers as biomarkers for immunotherapy in advanced non-small cell lung cancer (aNSCLC) patients A. Prelaj1 , S.E. Rebuzzi2 , P. Pizzutilo3 , M. Bilancia4 , M. Montrone3 , F. Pesola3 , V. Longo3 , G. Del Bene3 , V. Lapadula3 , F. Cassano3 , P. Petrillo3 , D. Bafunno3 , N. Varesano3 , V. Lamorgese3 , A. Mastranrdea3 , D. Ricci3 , A. Catino3 , D. Galetta3 1
Medical Oncology, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, Milan, Italy,2
Medical Oncology, IRCCS AOU San Martino - IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy,3
Thoracic Unit, Istituto Tumori Giovanni Paolo II, Bari, Italy,
4
Dipartimento Statistica, Istituto Tumori Giovanni Paolo II, Bari, Italy
Background: Immune-checkpoint inhibitors (ICIs) as second-line therapy showed an overall survival (OS) benefit, but only 18-20% of aNSCLC patients respond with a median progression-free survival (mPFS) of 2-4 months. The identification of bio-markers to select patients most likely to benefit from ICIs is still an unmet need in clini-cal practice.
Methods: We conducted a retrospective monocentric analysis in 154 aNSCLC patients receiving single-agent nivolumab or pembrolizumab as second-line (68%) and >3rd line (32%) therapy. We recorded complete blood cell count at baseline (T0), before second (T1) and third cycle (T2), assessing neutrophil-lymphocyte ratio (NLR), derived-NLR (dNLR) and lymphocyte-monocyte ratio (LMR). Statistical analyses (univariate and multivariate analysis) were performed to evaluate the correlation between overall response rate (ORR), PFS and OS and the change from baseline of NLR, dNLR and LMR at second (T0-T1) and third cycle (T0-T2). We divided bio-marker time-series into two groups of > 30% increase and <30% increase or decrease from baseline value.
Results: The only biomarker statistically significantly associated with survival out-comes was NLR. An increase of > 30% of NLR from baseline to the second cycle (NLR T0-T1) was associated with a worse PFS (3.7 vs 4.9 months, HR 1.52 95% CI 1.02 – 2.24; p¼ 0.04). We also observed a statistically significant correlation between ORR and the >30% increase of LMR from baseline to the second (LMR T0-T1; p < 0.001) and the third cycle (LMR T0-T2; p¼ 0.001).
Conclusions: According to the prognostic value of time-series of biomarkers at second and third cycle from baseline, patients who experienced an increase of > 30% of NLR after the first ICI cycle were associated with a worse PFS; also, an increase of > 30% of LMR after the first and second ICI administration lead to a better ORR.
Legal entity responsible for the study: The authors. Funding: Has not received any funding.
Disclosure: D. Galetta: Medical advisor: Bristol-Myers Squibb. All other authors have declared no conflicts of interest.
89P Treatment patterns and long-term survival for unresected stage III non-small cell lung cancer patients: A nationwide register study in Denmark A. Green1 , K.E. Olsen2 , M. Bliddal3 , H.N. Christensen4 , E. Jakobsen5 1
Epidemiology, Institute of Applied Economics and Health Research, Copenhagen, Denmark,2
Department of Pathology, Odense University Hospital, Odense, Denmark,
3
Odense Patient data Explorative Network, Odense University Hospital, Odense, Denmark,4
AstraZeneca, Copenhagen, Denmark,5
Department of Thoracic Surgery, Odense University Hospital, Odense, Denmark
Background: Patients with stage III non-small cell lung cancer (NSCLC) is a heteroge-neous population with resectable or unresectable tumors. Current standard of care for unresectable disease has since long been either curatively intended chemoradiotherapy (CRT) followed by active surveillance, or palliative treatment for CRT ineligible patients. Recently, published data have shown survival benefit of CRT followed by immunotherapy (durvalumab). The aim was to investigate long-term survival, treat-ment patterns, and characteristics for unresected stage III NSCLC patients in a real-life setting.
Methods: This nationwide study identified all stage III NSCLC patients diagnosed in Denmark during 2006-2015 in the Danish Cancer Registry. Patient and tumor data were linked with data on resection, CRT, radiotherapy only [RT], chemotherapy only [CT] and comorbidity from the National Patient Registry. Survival rates were estimated from date of diagnosis until death, migration, or end of study (2016) using Kaplan-Meier curves.
Results: During the study period, 33,747 patients were diagnosed with NSCLC, of which 7390 (22%) had stage III disease. Of these, 5919 (80%) patients were unresected, and they were older (mean age 69.2 vs. 65.8 years), more frequently men (55.0% vs. 51.5%), and had more comorbidity (39.8% vs. 33.6%one comorbidity) compared to the resected patients. Among the unresected patients, 40.5% received CRT, 15.1% RT,
15.6% CT, and 28.8% had no treatment. Patients receiving CRT were younger and had less comorbidity than patients receiving RT or CT only. The 5-year overall survival rates in the unresected group were: 10.6% CRT, 4.5% RT, and 3.6% for patients treated with CT. Among the resected stage III NSCLC patients, 42% survived5 years.
Conclusions: The poor long-term survival rates observed among unresected stage III NSCLC patients indicate a high unmet need for more effective therapy. New treatment strategies, including CRT followed by immunotherapy, might improve long-term out-comes for these patients. Increased utilization of biomarkers and correctly targeted therapies has the potential to personalize and improve treatment of stage III NSCLC. Legal entity responsible for the study: Institute of Applied Economics and Health Research Aps, Copenhagen, Denmark.
Funding: AstraZeneca.
Disclosure: H.N. Christensen: Employed: AstraZeneca. All other authors have declared no conflicts of interest.
90P Real-world treatment patterns, clinical practice and outcomes for locally advanced, non resectable, non-small cell lung cancer from the French ESME Lung database
N. Girard1 , M. Pe´rol2 , G. Simon3 , C. Audigier Valette4 , R. Gervais5 , D. Debieuvre6 , R. Schott7 , X. Quantin8 , B. Coudert9 , H. Lena10 , M. Carton1 , M. Robain3 , T. Filleron11 , C. Chouaid12 1
Institut Curie, Paris, France,2
Centre Le´on Be´rard, Lyon, France,3
Unicancer, Paris, France,4
Hospital Sainte Musse, Toulon, France,5
Centre Francois Baclesse, Caen, France,
6
Hopital Emile Muller, Mulhouse, France,7
Centre Paul Strauss Centre de Lutte contre le Cancer, Strasbourg, France,8
ICM Regional Cancer Institute of Montpellier, Montpellier, France,9
Centre Georges-Franc¸ois Leclerc (Dijon), Dijon, France,10
CHU de Pontchaillou, Rennes, France,11
Centre Claudius-Regaud, Toulouse, France,12
CH Intercommunal de Cre´teil, Cre´teil, France
Background: Approximately 30% of patients (pts) with non-small-cell lung cancer (NSCLC) are diagnosed with locally advanced disease, which is often unresectable. The historical standard of care (SoC) has been platinum-based chemoradiotherapy (CRT), based on data from clinical trials conducted in selected populations. As immunother-apy is being integrated in the treatment strategy, real-world evidence aiming at under-standing the current management of those patients is missing.
Methods: This study is an analysis of the Epidemio-Strategy and Medical Economics (ESME) Lung Data Platform, a multi-center real-life database using a retrospective data collection process. This database compiles data from patient’s Electronic medical records (EMR), inpatient hospitalisation records and Pharmacy records. 8514 pts from 20 centres with lung cancer treated between January 1st, 2015 and December 31st, 2016, were included.
Results: 822 pts with unresectable locally advanced NSCLC - 69% male, median age 65y, 61% ECOG PS0-1, 60% non-squamous histology - were included in the analysis. Treatment was initiated in 736 pts (analysis population): 39% concurrent CRT (cCRT), 17% sequential CRT (sCRT), 26% chemotherapy (CT) alone, 16% radiother-apy (RT) alone and 2% other therradiother-apy. For cCRT, 95% of pts received induction chemo-therapy before the concurrent phase, based on taxanes (32% of pts), vinorelbine (42% of pts), or pemetrexed (16% of pts); 35% of patients received consolidation chemother-apy. For sCRT, preferred platinum doublet chemotherapy regimens were based on tax-anes (39% of pts), vinorelbine (26% of pts), or pemetrexed (17% of pts). Radiotherapy was delivered to a total dose of 60-66 Gy for 84% (cCRT) and 71% (sCRT). After a median follow-up of 17 months, progression rate was 62%; progression occurred in the thorax, the brain, or at other sites in 42%, 19% and 38% of pts, respectively. Median PFS was 8.0 months (m) for the analysis population, 9.3 m (cCRT) and 11.6 m (sCRT). 24-month OS rate was 51%, 60%, and 52%, respectively.
Conclusions: Real world data support the use of CRT in locally advanced NSCLC, with similar outcomes than in landmark clinical trials.
Legal entity responsible for the study: UNICANCER. Funding: AstraZeneca.
Disclosure: N. Girard: Fees for attending scientific meetings, speaking, organizing research or consulting: AstraZeneca, Boehringer Ingelheim, Roche, SBMS, MSD, Lilly, Novartis, Pfizer, Amgen. M. Pe´rol, R. Gervais: Symposium, advisory board: AstraZeneca. C. Audigier Valette: Consultancy, Advisory board membership: AstraZeneca, Pierre Fabre. C. Chouaid: Fees for attending scientific meetings, speaking, organizing research or consulting: AstraZeneca, Boehringer Ingelheim, GSK, Roche, Sanofi Aventis, BMS, MSD, Lilly, Novartis, Bayer, Pfizer, Takeda, Amgen. All other authors have declared no conflicts of interest.
