Lunch & Poster Display session Poster Display session

27P - Single-nucleotide polymorphism variation (SNV): Possible candidates as predictive biomarkers to response and progression free survival (PFS) in cutaneous malignant melanoma (CMM) patients treated with immune checkpoint inhibitors (ICI)

Presentation Number
27P
Lecture Time
12:15 - 12:15
Speakers
  • F. Costa Svedman (Solna, Sweden)
Session Name
Lunch & Poster Display session
Location
Room B, Geneva Palexpo, Geneva, Switzerland
Date
12.12.2019
Time
12:15 - 13:15
Authors
  • F. Costa Svedman (Solna, Sweden)
  • M. Yang (Stockholm, Sweden)
  • R. Tuominen (Stockholm, Sweden)
  • S. Brage (Stockholm, Sweden)
  • V. Höiom (Stockholm, Sweden)

Abstract

Background

Treating CMM patients with ICI have significantly increased PFS and overall survival (OS) for this patient population. In order to further improve ICI efficacy we need to identify predictive biomarkers to foresee which patient would benefit from treatment. Extensive research is being performed globally but with very little focus on host genotype variations. The aim of this study was to identify host genetic markers that can predict treatment outcome in patients with metastatic CMM.

Methods

We have genotyped 49 patients with metastatic CMM treated with ICI at Karolinska University Hospital in Sweden. Blood samples were collected before treatment start. As platform we have used the Axiom Precision Medicine Research Arrays (Affymetrix ®). We have conducted genome-wide and targeted analysis of approximately 488,000 and 4000 single nucleotide variants respectively, using Partek Genomic Suite Software®.

Results

49 patients were included between July 2015 and August 2017, 22 females and 27 males. The median age was 68 years old (range 31 – 84). All patients had metastatic disease (33 M1C, 5 M1B, 11 M1A). ICI was first line treatment in most of the patients (n:40). Patients were treated with either nivolumab or pembrolizumab. Twenty-eight patients achieved disease control (with 8 complete responses) whereas 19 had progressive disease. Eleven patients were still responding at the cut-off date in 2018 November 30th, 1 missed follow-up and 2 were not included in the response analysis due to premature death. Median PFS was 6,9 months (range 0 – 40 months). The median OS was 19 months (range 0 – 40 months, 22 patients still alive at cut-off). We have in the targeted analysis identified one candidate significantly associated with both response and PFS. We are expanding the cohort and genotyping 40 additional patients.

Conclusion

Host genotype variations could identify novel predictive biomarkers candidates to ICI. Validation of our results with a bigger cohort is warranted.

Legal entity responsible for the study

Karolinska Institute.

Funding

Cancer Research Funds of Radiumhemmet, The Swedish Cancer Society and Knut and Alice Wallenberg Foundation.

Disclosure

All authors have declared no conflicts of interest.

Collapse
Lunch & Poster Display session Poster Display session

63P - Influence of nivolumab on epidemiology of infectious complications in patients with relapse or refractory Hodgkin’s lymphoma

Presentation Number
63P
Lecture Time
12:15 - 12:15
Speakers
  • Y. Rogacheva (Saint-Petersburg, Russian Federation)
Session Name
Lunch & Poster Display session
Location
Room B, Geneva Palexpo, Geneva, Switzerland
Date
12.12.2019
Time
12:15 - 13:15
Authors
  • Y. Rogacheva (Saint-Petersburg, Russian Federation)
  • M. Popova (Saint Petersburg, Russian Federation)
  • K. Lepik (Saint Petersburg, Russian Federation)
  • E. Kondakova (Saint Petersburg, Russian Federation)
  • Y. Zalyalov (Saint Petersburg, Russian Federation)
  • L. Stelmah (Saint Petersburg, Russian Federation)
  • A. Volkova (Saint Petersburg, Russian Federation)
  • I. Nikolaev (Saint Petersburg, Russian Federation)
  • O. Goloshchapov (Saint Petersburg, Russian Federation)
  • I. Barhatov (Saint Petersburg, Russian Federation)
  • S. Bondarenko (Saint Petersburg, Russian Federation)
  • I. Moiseev (Saint Petersburg, Russian Federation)
  • V. Baykov (Saint Petersburg, Russian Federation)
  • N. Mikhailova (, Russian Federation)
  • N. Klimko (Санкт-Петербург, Russian Federation)
  • B. Afanasyev (Saint Petersburg, Russian Federation)

Abstract

Background

The clinical development of checkpoint inhibitor-based immunotherapy has ushered in an exciting era of anticancer therapy. Despite many reports on anti PD-1 antibody therapy for the treatment of Hodgkin’s lymphoma (HL), the risk of infection among patients receiving nivolumab (nivo) is still unknown.

Methods

Between 2016 and 2018, 112 patients with r/r HL were observed and treated with nivo (3 mg/kg) in CIC 725. The median number of nivo courses received was 20 (range, 1-30). 18 patients underwent allo-HSCT after therapy with nivo. The median follow-up period was 1.4 years (1 month-2.6 year). All patients had a standard anti-infective prophylaxis and treatment according to the international guidelines.

Results

During salvage treatment with nivo of r/r HL 11 (10%) patients had documented infection episodes (n = 16): bacterial infections – 37.5% (n = 6), invasive fungal diseases (IFD) – 25% (n = 4) and viral infections – 37.5% (n = 6). The median time to infection episodes was 98 days (12-365) after first nivo administration. Incidence of bacterial infections in study cohort was 5.3% (n = 6). Two patients developed pneumonia, others with one: sinusitis, meningitis cause by Listeria meningitis, colitis and gonitis. Incidence of viral infections was 5.3% (n = 6): pneumonia associated with HHP-6 and CMV in 50% and generalized infections in 50% caused by HSV-1,2 and HHV-6. IFD were diagnosed in 3.6% patients (n = 4). The main etiology agent was Aspergillus spp. in 50%. Primary chemoresistant disease before nivo therapy was the only risk factor of infection complications during treatment of r/r HL (p = 0,029). Overall survival (OS) at 1 year after first nivo administration in study cohort was 96.5%. Only one death was attributed to infection; the patient died due to sepsis of unknown etiology.

Conclusion

Incidence of infectious complications in r/r HL treated with nivo was 10%. Etiology of infectious complications presented by bacterial infections –37.5%, invasive fungal diseases – 25% and viral infections – 37.5%. Primary chemoresistance was a risk factor for infection complications. Wherewith infections could be managed successfully and carry favorable prognosis.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Collapse
Lunch & Poster Display session Poster Display session

102P - Results from a phase II trial of pembrolizumab (P) plus gemcitabine (Gem) in patients (pts) with HER2-negative advanced breast cancer (ABC): GEICAM/2015-04 (PANGEA-Breast) study

Presentation Number
102P
Lecture Time
12:15 - 12:15
Speakers
  • L. De la Cruz Merino (Sevilla, Spain)
Session Name
Lunch & Poster Display session
Location
Room B, Geneva Palexpo, Geneva, Switzerland
Date
12.12.2019
Time
12:15 - 13:15
Authors
  • L. De la Cruz Merino (Sevilla, Spain)
  • J. Cruz (Santa Cruz de Tenerife, Spain)
  • J. Alonso (Murcia, Spain)
  • V. Quiroga Garcia (Badalona, Spain)
  • F. Moreno Anton (Madrid, Spain)
  • R. Andres (Zaragoza, Spain)
  • M. Santiesteban (Pamplona, Spain)
  • M. Ramos Vazquez (A Coruña, Spain)
  • M. Gion Cortes (Madrid, Spain)
  • J. Cortés (Barcelona, Spain)
  • N. Palazón Carrión (Seville, Spain)
  • I. Ceballos Lenza (San Cristobal de la Laguna, Santa Cruz de Tenerife, Canary Islands, Spain)
  • A. Soto (El Palmar, Spain)
  • M. Casas (San Sebastian de los Reyes, Spain)
  • S. Benito (San Sebastian de los Reyes, Spain)
  • S. Bezares Montes (San Sebastian de los Reyes, Madrid, Spain)
  • E. Holgado (Madrid, Spain)

Abstract

Background

This trial is based on a combination strategy with two immunostimulatory agents in the search of synergism that may induce responses with long-term clinical benefit in ABC pts. Safety data from the run-in-phase were published in ESMO IO 2018. Here, we report the results from the phase II part of the study.

Methods

HER2-negative ABC pts previously treated with anthracyclines and taxanes (unless contraindicated), ≤ 4 chemotherapy lines and/or ≥ 2 hormone therapy lines, and irrespective of PD-L1 status, were eligible. Study treatment consisted of 21-day cycles (cy) of P 200mg on day 1 and Gem 1250mg/m2 on days 1 and 8 until progressive disease (PD) or unacceptable toxicity, whatever occurred first. Primary objective was Objective Response Rate (ORR).

Results

Thirty-six pts were included in the first stage of a Simon’s design. Recruitment was stopped as only 5 pts presented an objective response (partial) (≥ 7 responses needed to continue recruiting pts). Median age was 52 years (range 31-77), 21 pts had triple negative disease, the majority of pts had an ECOG performance status ≤ 1 (n = 35), visceral involvement (n = 28) and ≥ 2 metastatic locations (n = 27). Median number of prior lines (any therapy) for ABC was 4 (range 0-11). Pts received a median of 4.5 cy of Gem and 4 cy of P (same range for both drugs, 1-24). The median relative dose intensity of P and Gem was 100% and 80%, respectively. Treatment discontinuation due to PD was reported on 29 pts. The ORR was 15.2% (95% confidence interval (CI) 5.1-31.9) and the Clinical Benefit Rate was 17% (95% CI 33.5-69.2); median duration of objective response was 4.3 months (mo) (95% CI 2.3-7.4), median Progression-Free Survival was 3.1 mo (95% CI, 2-4.3), and median Overall Survival was 7.9 mo (95% CI 6.5-10.3). Eight pts were on treatment ≥ 6 mo before PD (2 pts on 11.4 and 16.1 mo). Grade (G) ≥ 3 AEs related to the study treatment were reported on 14 pts (39%), being neutropenia the most common G3 (22.2%) and G4 (5.6%) AE.

Conclusion

P can be safely combined with Gem, the combination did not meet the efficacy objective in terms of ORR but 22.2% pts were on treatment ≥ 6 mo.

Clinical trial identification

NCT03025880.

Legal entity responsible for the study

GEICAM Spanish Breast Cancer Group.

Funding

MSD.

Disclosure

J. Cruz: Honoraria (self), Advisory / Consultancy: Glaxo; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pharmamar; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Pfizer. M. Ramos Vazquez: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer. J. Cortés: Honoraria (self), Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Celgene; Advisory / Consultancy: Cellestia; Honoraria (institution), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Biothera Pharmaceutical; Advisory / Consultancy: Merus; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: Erytech; Advisory / Consultancy: Athenex; Advisory / Consultancy: Polyphor; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (institution), Advisory / Consultancy: Servier; Honoraria (self), Honoraria (institution), Advisory / Consultancy: MSD; Advisory / Consultancy: GSK; Honoraria (self): Novartis; Honoraria (self), Honoraria (institution): Eisai; Honoraria (self), Honoraria (institution): Pfizer; Honoraria (self): Samsung Bioepis; Honoraria (institution), MedSIR (Stock, patent and intellectual property): Ariad Pharmaceuticals. Baxalta GMBH/Servier Affaires. Bayer Healthcare. Guardanth Health. Piqur Therapeutics. Puma C. Queen Mary University of London. Seagen. All other authors have declared no conflicts of interest.

Collapse
Gastrointestinal cancers: Updates Educational session

General discussion / Q&A

Lecture Time
16:20 - 16:30
Location
Room C, Geneva Palexpo, Geneva, Switzerland
Date
12.12.2019
Time
15:00 - 16:30
Lunch & Poster Display session Poster Display session

137P - Comparative analysis of the immune microenvironment in histological subtypes of lung and breast cancer using a tissue microarray (TMA) comprising invasive margin (IM) and tumour centre (TC)

Presentation Number
137P
Lecture Time
12:15 - 12:15
Speakers
  • M. Cumberbatch (Alderley Edge, United Kingdom)
Session Name
Lunch & Poster Display session
Location
Room B, Geneva Palexpo, Geneva, Switzerland
Date
12.12.2019
Time
12:15 - 13:15
Authors
  • M. Cumberbatch (Alderley Edge, United Kingdom)
  • L. Memeo (Washington, United States of America)
  • C. Womack (Washington, United States of America)
  • W. Kim (Seoul, Korea, Republic of)
  • M. Bhagat (Washington, United States of America)

Abstract

Background

Immunotherapy is proving successful in several tumour settings, although many cancer types remain less responsive. Pre-existing tumour infiltrating lymphocytes and PD-L1 expression associate with response to immunotherapy and cancers have been classified into response subtypes according to these biomarkers. To enable a simultaneous comparative assessment of the immune microenvironment in multiple tumour indications, we have constructed a multi-tumour TMA comprising matched cores for each donor from IM and TC.

Methods

In this study, we employed a TMA comprising cores taken from formalin fixed paraffin embedded (FFPE) non-treated surgical resections for donors diagnosed with squamous NSCLC (SCC; n = 13), adeno NSCLC (ADC; n = 12), small cell lung cancer (SCLC; n = 9), oestrogen receptor positive breast cancer (ER+BC; n = 12), Herceptin positive BC (Her2+BC; n = 12) and triple negative BC (TNBC; n = 12). Serial sections were stained by immunohistochemistry for several immune biomarkers (CD163, CD68, PD-L1, CD8, CD3, PD-1, Foxp3, CD4, CD20). Immune infiltrates were analysed by digital image analysis and PD-L1 was scored by a pathologist to deliver both the tumour proportion score (TPS) and the combined positivity score (CPS).

Results

By taking an average of all cores (IM and TC) for each disease indication, we demonstrate that SCC, ADC and TNBC are more highly infiltrated, and that while tumour PD-L1 (TPS) was absent in ER+BC and Her2+BC, the contribution from infiltrating immune cells (CPS) was greatest in SCC and TNBC. Interestingly, a reciprocal profile for CD163:CD68 was observed for LC versus BC, with the M2-like CD163+ macrophage/monocytic population exceeding the CD68+ macrophage population in BC, whereas the converse was observed for LC. Immune infiltrates were reduced in TC compared with IM, and distinct case-by-case immune microenvironments were revealed within each disease indication.

Conclusion

Using an immuno-oncology focussed TMA we have revealed distinct immune profiles in multiple tumour subtypes simultaneously, providing a valuable basis against which to profile novel immune targets.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Bhagat: Shareholder / Stockholder / Stock options, Officer / Board of Directors: TriStar Technolgoy Group. All other authors have declared no conflicts of interest.

Collapse
Brain tumours: Updates Educational session

Immune checkpoint inhibition for patients with brain metastasis: Patient selection and assessment of benefit

Lecture Time
10:00 - 10:20
Speakers
  • E. Le Rhun (Lille, CEDEX, France)
Session Name
Location
Room C, Geneva Palexpo, Geneva, Switzerland
Date
14.12.2019
Time
09:00 - 10:30
Authors
  • E. Le Rhun (Lille, CEDEX, France)
Lunch & Poster Display session Poster Display session

171P - Treatment (tx) patterns of patients with advanced renal cell carcinoma (aRCC) receiving first-line (1L) tx: Results from a cross-sectional real-world study

Presentation Number
171P
Lecture Time
12:15 - 12:15
Speakers
  • G. Zanotti (New York, United States of America)
Session Name
Lunch & Poster Display session
Location
Room B, Geneva Palexpo, Geneva, Switzerland
Date
12.12.2019
Time
12:15 - 13:15
Authors
  • G. Zanotti (New York, United States of America)
  • R. Kim (New York, NY, United States of America)
  • S. Krulewicz (Collegeville, United States of America)
  • J. Hall (Bollington, United Kingdom)
  • A. Leith (Bollington, United Kingdom)
  • A. Bailey (Bollington, United Kingdom)
  • F. Liu (Rockland, MA, United States of America)
  • M. Kearney (Darmstadt, Germany)

Abstract

Background

Personalised tx is key in aRCC. The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model determines prognosis of aRCC patients treated with systemic tx, helping guide treatment choice. This study examined real-world tx patterns and outcomes of 1L aRCC patients with differing IMDC status in the US.

Methods

Real-world data were drawn from the RCC Disease Specific ProgrammeTM; a cross-sectional study administered to oncologists, nephrologists and urologists in the US. Physicians completed patient record forms (PRFs) for up to the next 8 consulting RCC patients receiving active drug tx, from February - September 2019, plus additional optional PRFs for patients receiving/who had received either 1L nivolumab/ipilimumab combination tx or cabozantinib tx, where these patients were available. Study variables included patient demographics, background clinical information and tx patterns.

Results

Physicians (n = 82) provided data on 687 patients. 445 patients were receiving 1L tx at time of data abstraction. Of those receiving 1L tx, mean age was 64.2 years, and 69% of patients were male. 34% (n = 151) did not have a physician-assessed IMDC prognostic risk score, and 5% (n = 23) reported unknown. Of the 61% (n = 271) that had a physician-assessed IMDC prognostic risk score, 15% had a low risk, 63% had an intermediate risk and 21% had a high risk. In the intermediate and high risk group, tyrosine kinase inhibitor (TKI) monotherapy was the most common 1L therapy (45%, n = 103), followed by IO-IO combination (29%, n = 66).

Conclusion

ASCO and NCCN guidelines recommend IO-IO combination in patients with an intermediate or high IMDC risk. However, at the time of data collection, more patients meeting these criteria received TKI monotherapy than IO-IO combination; moreover, almost a third of 1L tx aRCC patients were not even assessed. Newly introduced IO-TKI combination tx, approved during the fieldwork period, could enable clinicians to offer patients personalised tx, irrespective of risk profile.

Legal entity responsible for the study

Pfizer Inc.

Funding

Pfizer Inc. (part of an alliance between Pfizer Inc. and Merck KGaA, Darmstadt, Germany).

Disclosure

G. Zanotti: Shareholder / Stockholder / Stock options: Pfizer; Full / Part-time employment: Pfizer. R. Kim: Full / Part-time employment: Pfizer; Shareholder / Stockholder / Stock options: Exelixis. S.P. Krulewicz: Shareholder / Stockholder / Stock options: Pfizer; Full / Part-time employment: Pfizer. J.P. Hall: Full / Part-time employment: Adelphi Real World. A. Leith: Full / Part-time employment: Adelphi Real World. A. Bailey: Full / Part-time employment: Adelphi Real World. F. Liu: Full / Part-time employment: EMD Serono, Inc. M. Kearney: Full / Part-time employment: Merck KGaA, Darmstadt, Germany; Shareholder / Stockholder / Stock options: Novartis Pharma; Shareholder / Stockholder / Stock options: UCB Pharma; Shareholder / Stockholder / Stock options: SPRL.

Collapse
Imaging and nuclear medicine Educational session

PET imaging to visualize immunotherapy

Lecture Time
17:40 - 18:00
Speakers
  • E. De Vries (Groningen, Netherlands)
Location
Room C, Geneva Palexpo, Geneva, Switzerland
Date
12.12.2019
Time
17:00 - 18:30
Authors
  • E. De Vries (Groningen, Netherlands)
Introduction to immunotherapy in cancer II Educational session

DOI session

Lecture Time
11:00 - 11:00
Location
Room A, Geneva Palexpo, Geneva, Switzerland
Date
11.12.2019
Time
11:00 - 12:15
Mini Oral session 2 Mini Oral session

130O - Association of long non-coding RNA biomarkers with clinically immune subtype and prediction of immunotherapy in patients with cancer

Presentation Number
130O
Lecture Time
08:10 - 08:15
Speakers
  • Y. Yu (Guangzhou, China)
Session Name
Location
Room C, Geneva Palexpo, Geneva, Switzerland
Date
13.12.2019
Time
08:00 - 09:00
Authors
  • Y. Yu (Guangzhou, China)
  • W. Zhang (Zhanjiang, China)
  • A. Li (Zhanjiang, China)
  • Y. Chen (Guangzhou, China)
  • Y. Wang (Guangzhou, China)
  • Y. Zhang (Guangzhou, China)
  • Z. He (Guangzhou, China)
  • Q. Ou (Guangzhou, China)
  • R. Liu (Zhanjiang, China)
  • E. Song (Guangzhou, China)
  • H. Yao (Guangzhou, China)

Abstract

Background

Long non-coding RNAs (lncRNAs) are involved in innate and adaptive immunities in cancers by mediating the functional states of immunologic cells, pathways, and genes. However, whether lncRNAs could serve as effective biomarkers for molecular classification and prediction of cancer immunotherapy efficacy are largely unknown.

Methods

This study analyzed lncRNA and genomic data of 348 atezolizumab-treated bladder cancer patients from phase II IMvigor 210 trial and 3,021 patients in lung cancer, breast cancer, bladder cancer, and melanoma cohorts from The Cancer Genome Atlas. We investigated lncRNA-based immune subtypes associated with cancer immunotherapy efficacy. We built a novel lncRNA score using computational algorithms and integrated it with programmed-death ligand 1 (PD-L1) expression and tumor mutation burden (TMB) to achieve accurate immunotherapeutic prediction.

Results

The results from IMvigor 210 trial showed that four distinct microenvironment-based subtypes characterized by lncRNA expression and tumor specific cytotoxic T lymphocytes (CTLs) infiltration had significant difference in overall survival (OS) (hazard ratio [HR] 0.77, 95%CI 0.67–0.88; P = 0.0002), with the greatest benefits in Immune-Active Class, followed by Immune-Exclusion Class, Immune-Dysfunctional Class, and Immune-Desert Class. High NKILA lncRNA expression was identified as a negative predictor of immunotherapeutic OS benefits and a critical regulator of dysfunctional immune response. Patients with low- versus high- lncRNA scores were associated with significantly longer OS in IMvigor 210 trial (HR 0.32, 95% CI 0.24–0.42; P < 0.0001) and across various cancer types. Multiomics comprising lncRNA score, PD-L1 expression and TMB led to more precise OS prediction in IMvigor 210 trial (20-month AUC=0.80) and in melanoma immunotherapy cohort (24-month AUC=0.89) compared with variable alone.

Conclusion

We suggested immunotherapy for patients in Immune-Functional Class, especially for those in high CTL Immune-Active Class. Multiomics comprising lncRNA score, PD-L1 expression and TMB could accurately predict immunotherapy efficacy.

Legal entity responsible for the study

Herui Yao.

Funding

Grants from the National Natural Science Foundation of China (81372819, 81572596, U1601223), the Natural Science Foundation of Guangdong Province (2017A030313828), the Guangzhou Science and Technology Program (201704020131), the Sun Yat-Sen University Clinical Research 5010 Program (2018007).

Disclosure

All authors have declared no conflicts of interest.

Collapse
Lunch & Poster Display session Poster Display session

17P - Association of lung immune prognostic index (LIPI) with survival of first line immune checkpoint inhibitors single agent or in combination with chemotherapy in untreated advanced NSCLC patients

Presentation Number
17P
Lecture Time
12:15 - 12:15
Speakers
  • F. Blanc-Durand (Paris, France)
Session Name
Lunch & Poster Display session
Location
Room B, Geneva Palexpo, Geneva, Switzerland
Date
12.12.2019
Time
12:15 - 13:15
Authors
  • F. Blanc-Durand (Paris, France)
  • E. Auclin (Paris, France)
  • D. Planchard (Villejuif, France)
  • S. Ponce Aix (Madrid, Spain)
  • L. Hendriks (Maastricht, Netherlands)
  • I. Sullivan (Barcelona, Spain)
  • D. Saravia (Miami, FL, United States of America)
  • B. Routy (Montreal, Canada)
  • R. Lopez Castro (Valladolid, Spain)
  • S. Pilotto (Verona, Italy)
  • F. Aboubakar (Brussels, Belgium)
  • E. Kassouf (St-Charles-Borromée, Quebec, Canada)
  • A. Rodriguez (Barcelona, Spain)
  • A. Amores Martin (Salamanca, Spain)
  • M. Bluthgen (Buenos Aires, Argentina)
  • B. Duchemann (Bobigny, CEDEX, France)
  • C. Caramella (Villejuif, France)
  • E. Nadal (Barcelona, Barcelona, Spain)
  • B. Besse (Villejuif, CEDEX, France)
  • L. Mezquita (Villejuif, France)

Abstract

Background

The Lung Immune Prognostic Index (LIPI), combining the derived neutrophils/[leucocytes minus neutrophils] ratio (dNLR) and lactate dehydrogenase (LDH), has been associated with survival for ICI-single agent in large cohorts of refractory advanced NSCLC. However the role of LIPI in untreated NSCLC patients has not been explored yet. We assessed the value of LIPI in the front-line setting of advanced NSCLC patients (pts) treated with ICI-single agent or in combination with chemotherapy and compared to a cohort of pts treated exclusively with chemotherapy (CT).

Methods

Retrospective multicenter study of pts treated in first-line ICI single agent if PD-L1 ≥50% (ICI-cohort), or in combination with chemotherapy (Combo-cohort) from 15 centers worldwide. A control cohort with pts treated with platinum-based CT (CT-cohort) was extracted from the prospective MSN study. LIPI was calculated as previously reported. We correlated pretreatment LIPI with overall survival (OS) in the 3 cohorts.

Results

A total of 470 pts were enrolled in the three cohorts between 2011 and 2019. Median follow-up is 13.9 months. In the ICI-cohort (N = 252), 165 (65%) were male, with median age of 67, 195 (77%) with PS ≤ 1. Based on LIPI (available for 195 pts): 81 (42%) were considered good, 86 (44%) intermediate and 28 (14%) poor group. In the combo-cohort (N = 98), 71 (72%) were male, with median age of 66, and 84 (86%) with PS ≤ 1. Based on LIPI (available for 69): 23 (33%) were good group, 34 (49%) intermediate and 12 (17%) poor group. In the CT-cohort (N = 120), no differences were observed by LIPI groups. The impact of LIPI groups in the 3 cohorts is summarized in the table.

Table: 17P OS and PFS in the 3 cohorts; OS according to the LIPI groups

OSICI-cohortCombo-CohortChemo-cohort
Median PFS8.5m. [6.6-11.8]9.6m. [6.7-11]5.7m. [5.1-6.6]
Median OS21.3 m. 12.8-NR]24.7m. [14.9-25.7]13.8m. [9.6-15.3]
LIPI good Median OSNR [17.36-NR]25.7m. [25.6-NR]14.4 m. [9.6-18.1]
LIPI intermediate Median OSNR [9.2-NR]16.9 m. [12.8-NR]13.8 m. [8.5-15.8]
LIPI poor Median OS7.9m. [2.3-NR]6.2m. [5.7-NR]6.5 m. [6-NR]
P valueP = 0.01P = 0.02P = 0.19

NR: not reached; OS: overall survival; PFS: progression-free survival.

Conclusion

Pretreatment LIPI correlates with ICI survival in monotherapy and in combination with chemotherapy in front-line in advanced NSCLC pts. The correlation is not statistically significant in the chemotherapy alone group. The value of LIPI for ICI upfront should be explored in prospective clinical trials.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

E. Auclin: Travel / Accommodation / Expenses: Mundipharma; Speaker Bureau / Expert testimony: Sanofi Genzyme. D. Planchard: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Boehringer; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Celgene; Advisory / Consultancy: Daiichi Sankyo; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Eli Lilly; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Merck; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: prIME Oncology; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Peer CME; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche. L. Hendriks: Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Research grant / Funding (self): Boehringer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy: Lilly; Honoraria (self): Quadia. B. Besse: Honoraria (institution): AbbVie; Honoraria (institution): Amgen; Honoraria (institution): AstraZeneca; Honoraria (institution): Biogen; Honoraria (institution): Blueprint Medicines; Honoraria (institution): Bristol-Myers Squibb; Honoraria (institution): Celgene; Honoraria (institution): Eli Lilly; Honoraria (institution): GSK; Honoraria (institution): Ingnyta; Honoraria (institution): Ipsen; Honoraria (institution): Merck KGaA; Honoraria (institution): MSD; Honoraria (institution): Nektar; Honoraria (institution): Onxeo; Honoraria (institution): Pfizer; Honoraria (institution): Pharma Mar; Honoraria (institution): Sanofi; Honoraria (institution): Spectrum Pharmaceuticals; Honoraria (institution): Takeda. L. Mezquita: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche diagnostics; Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: Tecnofarma; Speaker Bureau / Expert testimony, Research grant / Funding (self): AstraZeneca; Travel / Accommodation / Expenses: Chugai. All other authors have declared no conflicts of interest.

Collapse
Lunch & Poster Display session Poster Display session

53P - Immune-related adverse events associated with immune-checkpoint inhibitors: A single center experience

Presentation Number
53P
Lecture Time
12:15 - 12:15
Speakers
  • N. Samanci (Istanbul, Turkey)
Session Name
Lunch & Poster Display session
Location
Room B, Geneva Palexpo, Geneva, Switzerland
Date
12.12.2019
Time
12:15 - 13:15
Authors
  • N. Samanci (Istanbul, Turkey)
  • K. Oruc (Istanbul, Turkey)
  • S. Bedir (Istanbul, Turkey)
  • E. Celik (Istanbul, Turkey)
  • E. Degerli (Istanbul, Turkey)
  • S. Derin (Istanbul, Turkey)
  • F. Demirelli (Istanbul, Turkey)
  • M. Ozguroglu (Istanbul, Turkey)

Abstract

Background

Clinical trials have demonstrated the benefit of immune-checkpoint inhibitors (ICIs) for many cancer types. With the widespread use of ICIs, we are facing challenges in the management of immune-related adverse events(irAEs). It is extremely important for physicians to be aware of early recognition and immediate treatment of irAEs. In this study, we aimed to characterize the spectrum of toxicity, management, and outcomes for irAEs.

Methods

Between January 2015 and December 2018, patients who were treated with at least one ICIs in clinical trials, expanded access programs or in routine practice in Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine were included in this study. Clinical and laboratory parameters were collected retrospectively to determine the incidence of irAEs, risk factors, and their association with treatment outcomes. All irAEs were graded using the CTCAE v4.0.

Results

A total of 255 patients were retrospectively evaluated. Of these 71 (27.8%) patients developed irAEs. 52(73.2%) of the patients were male, 19 (26.8%) were female. All patients have ECOG performance status 0 -1. More than 2 irAEs were detected in 16 (6.2%) patients. A total of 3177 doses were given with 93 episodes of any grade irAEs. There were 22 irAEs (23.7%) reported as grade 1, 49 (52.7%) as grade 2, 19 (20.4%) as grade 3, and 3 (3.2%) as grade 4. The most common among them were pneumonitis (n:15), hepatitis (n:13), hypothyroidism (n:13) and dermatitis (n:12). 3 patients were reported to develop grade 4 pneumonitis, toxic epidermal necrolysis and thrombocytopenia. There were 9 immune related deaths in our study. In 4 patients same irAEs recurred upon rechallenge of the ICIs. 39 of irAEs (41.9%) occurred after anti PD1, 47 (50.5 %) occurred after anti PDL1, 7 (7.5%) occurred after combination of anti CTLA4+ anti PDL1.

Conclusion

With the increased use of immunotherapeutic agents in oncology clinics, increased awareness and early recognition are required for effective management of irAEs and improved treatment outcomes. We believe that this study will have a significant impact on current and future service delivery in oncology units.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Collapse