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Proffered paper session - Breast cancer, early stage Proffered Paper session

186O - Tumor-infiltrating lymphocytes (TILs) as an independent prognostic factor for early HER2+ breast cancer patients treated with adjuvant chemotherapy and trastuzumab in the randomized ShortHER trial.

Presentation Number
186O
Lecture Time
16:51 - 17:03
Speakers
  • Maria Vittoria Dieci (Padova, IT)
Location
ICM - Room 13, ICM München, Munich, Germany
Date
19.10.2018
Time
16:00 - 17:30

Abstract

Background

TILs are an established prognostic factor for triple negative breast cancer. We investigated the prognostic role of TILs for HER2+ early breast cancer patients enrolled in the prospective ShortHER trial.

Methods

The ShortHER study randomized 1254 patients with HER2+ early breast cancer to receive 9 weeks vs 1 year of adjuvant trastuzumab combined with chemotherapy (Conte, ASCO 2017). TILs were assessed for 855 cases on centralized HES slides according to recommendations (Salgado, Ann Oncol 2015). Metastasis-free survival (MFS) was calculated from randomization to distant disease recurrence or death. Median follow up was 72 months.

Results

Median TILs was 5% (Q1-Q3 1%-15%). Higher TILs were associated with hormone receptor-negative status (p < 0.001) and age <60 years (p = 0.008). There was no association with stage and PIK3CA mutation. Increased TILs were associated with better MFS (HR 0.69, 95%CI 0.54-0.88 for each 10% TILs increment, p = 0.003). 5-yrs MFS rates were 91%, 94% and 100% for TILs<20%, TILs > =20% & <50% and TILs > =50% (p = 0.013). Multivariable cox models confirmed TILs as independent prognostic factor (Table).

MULTIVARIATE COX MODELS FOR MFS
FactorsAll patients
Hormone Receptor neg
Hormone Receptor pos
HR (95% CI)pHR (95% CI)pHR (95% CI)p
TILs 10% increase0.67 (0.52-0.86)0.0010.72 (0.53-0.97)0.0310.57 (0.36-0.91)0.017
HR pos vs neg0.63 (0.39-1.00)0.049----
Stage I-II vs III0.31 (0.20-0.50)<0.0010.27 (0.13-0.59)0.0010.33 (0.19-0.60)<0.001
Age >60 vs < 601.02 (0.65-1.60)0.9361.44 (0.69-3.02)0.3370.82 (0.45-1.47)0.501

The association between 10% TILs increments and MFS was significant in the short (HR 0.49, 95%CI 0.29-0.82, p = 0.006) but not in the long arm (HR 0.84, 95%CI 0.65-1.10, p = 0.212). Patients with TILs <20% benefitted from long treatment (HR 0.76, 95%CI 0.60-0.97, p = 0.024), whereas for patients with TILs > =20% the HR favored the short arm (HR 2.79, 95%CI 0.98-7.96, p = 0.055; 8 events only). Interaction test showed p = 0.064 (arm*10% TILs increase) and p = 0.019 (arm*TILs binary variable with 20% cutoff).

Conclusions

TILs are an independent prognostic factor for HER2+ early breast cancer patients treated with adjuvant chemotherapy and trastuzumab. Integration of TILs in prognostic algorithms can help refining risk stratification and guiding therapeutic de-escalation.

Clinical trial identification

EudraCT 2007-004326-25 Start date: 2007-11-15.

Legal entity responsible for the study

University of Modena and Reggio Emilia; University of Padova.

Funding

Agenzia Italiana del Farmaco (AIFA).

Disclosure

P.F. Conte: Speaker's bureau: Roche Genentech; Research funding (Institution): Roche. V. Guarneri: Research funding (Institution): Roche. All other authors have declared no conflicts of interest.

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Proffered paper session - Breast cancer, early stage Proffered Paper session

187O - High-dose chemotherapy (HDCT) with hematopoietic stem cell transplantation (HSCT) in high-risk breast cancer (BC) patients with _4 involved axillary lymph nodes (ALN): 20-year follow-up of a randomized phase 3 study

Presentation Number
187O
Lecture Time
17:03 - 17:15
Speakers
  • Tessa G. Steenbruggen (Amsterdam, NL)
Location
ICM - Room 13, ICM München, Munich, Germany
Date
19.10.2018
Time
16:00 - 17:30

Abstract

Background

Adjuvant HDCT for high-risk BC is not beneficial overall compared to conventional chemotherapy at the cost of considerable toxicity. HDCT benefit, however, may be present in very high-risk patients (i.e. >9 involved ALN) and in triple negative (TN) BC patients, although long-term results are lacking for most initial studies. We evaluated long-term outcome of a randomized phase 3 study, conducted from 1993 to 99.

Methods

Patients aged <56 years with early BC and ≥4 involved ALN were randomized to either conventional chemotherapy or HDCT as adjuvant systemic treatment. The conventional arm consisted of 5x fluorouracil, epirubicin and cyclophosphamide (FEC) 3-weekly. In the HDCT arm, the 5th FEC was replaced by cyclophosphamide 6000 mg/m2, thiotepa 480 mg/m2, carboplatin 1600 mg/m2 and supported with autologous HSCT (Rodenhuis, NEJM 2003). We collected 20-year follow-up data from medical records, general practitioners, and the Netherlands Cancer Registry. Endpoints were relapse free survival (RFS), overall survival (OS), BC specific survival (BCSS), and safety based on intention to treat analyses.

Results

885 patients (64% 4-9 ALN, 36% >9 ALN; 53% ER+/HER2-, 23% HER2+, 16% TN, 8% unknown) were randomized to FEC (n = 443) or HDCT (n = 442). The table shows efficacy results of univariable Cox models. With 20 years median follow-up, relapse or death occurred in 272 patients (61%) who received FEC vs in 257 (58%) HDCT patients (HR 0.88; 95% CI 0.74-1.05). The effect of HDCT compared to FEC was most pronounced in patients with >9 involved ALN and in TNBC patients. In 138 TNBC patients the 20-year OS estimate was 52% after HDCT vs 39% after FEC. Long-term safety and BCSS will also be presented at the meeting.

RFSHDCTFEC
N20 yr (%)95% CI20 yr (%)95% CIHR95% CIp
All8854237-473833-430.880.74-1.050.15
4-9 ALN5684338-504438-501.000.81-1.250.97
>9 ALN3173931-472721-360.710.54-0.940.02
ER+/HER2-4694034-473630-430.830.66-1.040.11
HER2+2053830-494233-521.150.80-1.630.46
TN1385140-653424-480.660.42-1.030.07
OSHDCTFEC
N20 yr (%)95% CI20 yr (%)95% CIHR95% CIp
All8854541-504137-460.890.74-1.060.18
4-9 ALN5684640-524842-541.010.81-1.270.91
>9 ALN3174437-533023-380.720.54-0.950.02
ER+/HER2-4694640-534034-470.810.64-1.030.09
HER2+2054032-514637-561.150.80-1.660.44
TN1385241-653929-520.710.45-1.120.14

Conclusions

Long-term follow-up confirms survival benefit of HDCT in BC patients with >9 involved ALN and suggests benefit in TNBC patients.

Clinical trial identification

NCT03087409.

Legal entity responsible for the study

High-risk breast cancer study group from the Netherlands Working Party on Autologous Transplantation in Solid Tumors.

Funding

Has not received any funding.

Disclosure

T.G. Steenbruggen: Financial support: Memidis Pharma unrelated to the submitted work. V.C.G. Tjan-Heijnen: Research funding through grants institution: Eisai, Roche, Pfizer, Novartis, and AstraZeneca; Compensation for service as a consultant: AstraZeneca, Pfizer, Novartis, and Roche; Honoraria: Pfizer, Roche, and Novartis; Travel expenses: Pfizer, Novartis, and Roche. S.C. Linn: Institutional research funding: AstraZeneca, Amgen, BMS, Genentech, Roche, and Sanofi; Advisory board member: AstraZeneca, Novartis, Roche and Sanofi. E.G.E. de Vries: Consulting/advisory board fees: Synthon, Pfizer and Sanofi; Grants: Novartis, Amgen, Roche/Genentech, Regeneron, Chugai, Synthon, AstraZeneca, Radius Health, CytomX Therapeutics and Nordic Nanovector, all to the hospital and unrelated to the submitted work. G.S. Sonke: Institutional research funding: AstraZeneca, Merck, Novartis, Roche, unrelated to the submitted work. All other authors have declared no conflicts of interest.

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Proffered paper session - Translational research Proffered Paper session

50O - Plasma cell-free DNA (cfDNA) assays for early multi-cancer detection: the Circulating Cell-Free Genome Atlas (CCGA) study

Presentation Number
50O
Lecture Time
09:15 - 09:27
Speakers
  • Minetta C. Liu (Rochester, US)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
20.10.2018
Time
09:15 - 10:45

Abstract

Background

A noninvasive cfDNA blood test detecting multiple high-mortality cancers at early stages when treatment is more likely effective could decrease cancer mortality. CCGA (NCT02889978) is a prospective multi-center observational study to develop a plasma cfDNA-based multi-cancer detection assay.

Methods

Prospectively collected clinically evaluable samples (N = 2402) from non-cancer controls (C) and participants with newly diagnosed untreated cancer (pts; 20 tumor types, all stages) were divided into training (n = 1458; 580 C, 878 pts) and test (n = 944; 368 C, 576 pts) sets and analyzed as a preplanned substudy. Prototype sequencing assays included paired cfDNA/white blood cell (WBC, 60000X) targeted sequencing, paired cfDNA/WBC whole genome sequencing (30X), cfDNA whole genome bisulfite sequencing (WGBS, 30X). Sensitivity was estimated at 98% specificity. Cancers with >5 pts in training and test are reported.

Results

Overall, pts (all stages) and C had similar age, smoking status, and gender. WGBS returned the highest sensitivity and is included here; results were consistent across the targeted, WGS, and WGBS assays, and will be reported in full. WBC signal was used to correct for clonal hematopoiesis. Stage I-IV cancer detection was consistent in training and test sets. In training, cancer-specific sensitivities (high-signal cancers) ranged from 54-92% and will be reported in detail. In individual cancers in the test set, numbers and sensitivity (95% CI) were: 22 hormone receptor negative breast (36%, 17-59), 45 colorectal (60%, 44-74), 7 esophageal (43%, 10-82), 12 head & neck (50%, 21-79), 15 hepatobiliary (73%, 45-92), 47 lung (70%, 55-83), 22 lymphoma (64%, 41-83), 7 ovarian (71%, 29-96) and 23 pancreatic (74%, 52-90). Results were also consistent between training and test sets in stage I-III and stage IV cancers.

Conclusions

A cfDNA-based blood test detected multiple cancers at various stages consistently in training and test sets. This approach is promising as a multi-cancer early detection test, including for high mortality unscreened cancers where stage shift can impact mortality. Further assay and clinical development of a multi-cancer cfDNA test in large-scale clinical studies, including CCGA, is ongoing.

Clinical trial identification

NCT02889978.

Legal entity responsible for the study

GRAIL, Inc.

Funding

GRAIL, Inc.

Editorial Acknowledgement

Writing support provided by Megan P. Hall, PhD (GRAIL, Inc., Menlo Park, CA).

Disclosure

M.C. Liu: Advisory board member: GRAIL, Inc. E. Klein: Consultant: GRAIL Inc., GenomicHealth, GenomeDx. E. Hubbell: Employee: GRAIL, Inc. with options to hold stock; Stock: ThermoFisher. T. Maddala, A.M. Aravanis, J.F. Beausang, D. Filippova, S. Gross, L. Shen, N. Zhang, O. Venn, J. Yecies, S. Patel, A-R. Hartman: Employee: GRAIL, Inc. with options to hold stock in the company. A. Jamshidi, K. Kurtzman: Employee: GRAIL, Inc. with options to hold stock in the company; Stock: Illumina. M. Seiden: Employee and stocks: McKesson. G.Oxnard: Advisory board member, consultant: Inivata; Honorarium: Guardant Health, Sysmex, BioRad; Consultant: DropWorks, AstraZeneca, GRAIL, Inc. All other authors have declared no conflicts of interest.

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Proffered paper session - Translational research Proffered Paper session

1336O - Unbiased genomewide screening of circulating plasma DNA for cancer detection

Presentation Number
1336O
Lecture Time
09:27 - 09:39
Speakers
  • Liesbeth Lenaerts (Leuven, BE)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
20.10.2018
Time
09:15 - 10:45

Abstract

Background

Early cancer diagnosis might significantly improve survival rates. As circulating tumor (ctDNA) carries cancer-specific modifications, it has great potential as a non-invasive biomarker for detection of incipient tumors.

Methods

Cell-free DNA (cfDNA) samples of 1006 elderly people (389 men and 617 women), not having any history of malignancy, were collected between October 2015 and September 2017 and analyzed via our cfDNA analysis pipeline, coined GIPseq (Genomic Imbalance Profiling from cfDNA SEQuencing). GIPseq profiles were screened for the presence of (sub)chromosomal copy number variations (CNVs) that might be predictive for a malignancy. When imbalances were detected, a 6-month clinical follow-up was performed.

Results

In 3% of participants (20 men and 10 women) an aberrant GIPseq profile was detected. Detected gains and losses in cfDNA were reproducible upon analysis of a second plasma sample taken within a mean time span of 139 days. Subsequent whole body MRI screening led to the identification of 3 hematological malignancies (1 Hodgkin stage II; 1 non-Hodgkin stage IV; 1 myelodysplastic syndrome with excess blasts stage II) and 2 cases with monoclonal B-cell lymphocytosis, a potential precursor of B-cell malignancy. The CNVs detected in plasma cfDNA were confirmed to be tumor-specific upon shallow sequencing of biopsy DNA. In 24 individuals, chromosomal anomalies in cfDNA could not be linked to a malignancy. Eleven of these cases had a CNV on chromosome 5 (5q-, n = 2 cases), 15 (15+, n = 5) or 20 (20q-, n = 4) in cfDNA, which was found to originate from peripheral blood cells in 7 of them. Previous studies found that mosaicisms for large chromosomal anomalies are detectable in cellular DNA of peripheral blood and buccal cells in about 2% of elderly people, predicting a 5 to 10-fold enhanced risk of a subsequent cancer. For 16 of our study participants, the cellular origin of the chromosomal anomalies detected in cfDNA remains unknown.

Conclusions

Our results deliver unique data on the presence of a wide range of (cancer-related) chromosomal aberrations detectable in cfDNA of elderly people. A long-term follow-up of these people is planned to further explore the biological and clinical significance of the detected anomalies.

Legal entity responsible for the study

University Hospitals Leuven.

Funding

Research Foundation - Flanders.

Disclosure

All authors have declared no conflicts of interest.

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Proffered paper session - Translational research Proffered Paper session

51O - Pan-cancer assessment of BRCA1/2 genomic alterations (GAs) by comprehensive genomic profiling (CGP) of tissue and circulating tumor DNA (ctDNA).

Presentation Number
51O
Lecture Time
09:54 - 10:06
Speakers
  • Neeraj Agarwal (Salt Lake City, US)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
20.10.2018
Time
09:15 - 10:45

Abstract

Background

Whether somatic or germline, biallelic BRCA1/2 loss of function (LOF) results in homologous recombination deficiency (HRD) and is associated with sensitivity to PARP inhibitors (PARPi) in ovarian and breast cancer. We evaluate the pan-cancer landscape of BRCA1/2 GAs in tissue and ctDNA.

Methods

Hybrid capture-based CGP was performed in a CLIA/CAP lab using a tissue-based assay (FoundationOne) of 315 cancer-related genes or a blood-based ctDNA assay of 62 genes (FoundationACT), including the complete exonic regions of BRCA1 and BRCA2. Genomic profiles were available for >90,000 tissue and >5,000 ctDNA samples.

Results

We identified pathogenic BRCA GAs in 5% of tissue and 6% of ctDNA specimens, with BRCA GAs most frequently identified in ovarian carcinoma (15%), prostate (11%), breast (9%), endometrial (6%), and colorectal [CRC] (4%). Somatic-like BRCA GAs were most frequent in CRC (85%), non-small cell lung cancer [NSCLC] (64%), and prostate cancer (56%), but were also frequent in breast (32%) and ovarian cancers (42%). In tissue-based testing, we observe high frequencies of BRCA loss-of-heterozygosity (LOH) in ovarian and breast carcinomas (94% and 82% of BRCA point GAs), intermediate levels in prostate and pancreatic carcinomas (69% and 66%), and low levels in NSCLC, melanoma, and CRC (40%, 20%, 18%). BRCA LOF was associated with an elevated % genomic LOH in most tumor types (ovarian, breast, pancreatic, NSCLC, CRC, melanoma, and prostate; p < 1e-10). An index case of a prostatic carcinoma with homozygous BRCA alteration, and a genomic LOH score in the top quintile, showed a robust response to a PARPi. Comparison of tissue versus ctDNA revealed highly similar BRCA alteration frequencies (r = 0.94) across disease groups. ctDNA concordance with BRCA-altered tissue (n = 56) was 73% (41/56) overall, and concordance was associated with ctDNA fraction.

Conclusions

The frequencies of BRCA GAs observed here suggest HRD-targeted therapies warrant further investigation in carcinomas beyond ovarian, breast, and prostate. CGP of ctDNA may be a convenient and highly sensitive method for identifying such cases although it may need to be complemented with tissue testing for bi-allelic assessment of BRCA loci.

Legal entity responsible for the study

Huntsman Cancer Institute.

Funding

Has not received any funding.

Disclosure

N. Agarwal: Consultant or advisor: Pfizer, Exelixis, Cerulean Pharma, Medivation/Astellas, Eisai, Merck, Novartis, EMD Serono, Clovis Oncology, Genentech/Roche, Bristol-Myers Squibb, AstraZeneca, and Nektar; Research funding: Bayer, Bristol-Myers Squibb, GlaxoSmithKline, Medivation, Takeda, Novartis, Pfizer, BN ImmunoTherapeutics, Exelixis, Tracon Pharma, Rexahn Pharmaceuticals, Amgen. E.S. Sokol: Employment: Foundation Medicine, Inc. P. Lara Jr.: Consultant or advisor: Exelixis, Pfizer, Novartis, AstraZeneca, Bayer, Genentech/Roche, Celgene, Janssen Biotech, Bristol-Myers Squibb, Abbvie, Turnstone Bio; Research funding: Millennium, Polaris, GlaxoSmithKline, Genentech/Roche, Aragon Pharmaceuticals, Janssen Biotech, Heat Biologics, Tracon Pharma, Merck, Pharmacyclics, Incyte; Honoraria: Pfizer. J.S. Ross: Employment, leadership, stock, other ownership interests, research funding: Foundation Medicine, Inc. V.A. Miller: Employment, leadership, stock, other ownership interests: Foundation Medicine, Inc.; Patents, royalties, other intellectual property: Periodic royalties related to T790M patent awarded to Memorial Sloan Kettering Cancer Center. A.W. Welsh: Employment, travel, accommodations, expenses, stock, other ownership interests: Foundation Medicine, Inc. J.P. Gregg: Consultant or advisor: AstraZeneca, Bristol-Myers Squibb, Abbvie, Roche; Speakers' bureau: AstraZeneca, Foundation Medicine, Inc. G.M. Frampton: Employment, stock, other ownership interests: Foundation Medicine, Inc. S.M. Ali: Employment, patents, royalties, other intellectual property: Foundation Medicine, Inc.; Stock, other ownership interests: Exelixis, Blueprint Medicines, Agios; An immediate family member: Patent royalties: Seres Health. J. Chung: Employment, stock, other ownership interests: Foundation Medicine, Inc.

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Proffered paper session - Translational research Proffered Paper session

52O - Circulating tumour DNA analysis predicts relapse following resection in stage II and III melanoma

Presentation Number
52O
Lecture Time
10:06 - 10:18
Speakers
  • Lavinia Tan (Melbourne, AU)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
20.10.2018
Time
09:15 - 10:45

Abstract

Background

Adjuvant immunotherapy and BRAF-targeted therapies have shown improved relapse-free survival (RFS) in patients (pts) with resected melanoma. There is a critical need to develop biomarkers to stratify pts based on risk of relapse given the cost and toxicities with these therapies.

Methods

Droplet digital PCR was used to detect known mutations in circulating tumour DNA (ctDNA) from 112 pts with resected stage II-III melanoma who consented to prospective serial plasma and risk-adapted F-18-fluoro-deoxyglucose positron emission tomography (FDG-PET) monitoring. External validation was performed in a prospective independent cohort.

Results

In 92/112 pts who did not receive adjuvant therapy, 55/92 (60%) pts relapsed at a median follow-up of 21 months. Plasma samples were available in 67/92 pts at baseline and 59/92 pts postoperatively (median 2 weeks post surgery). ctDNA was detected at baseline and postoperatively in 21/67 (31%) pts and 15/59 (25%) pts respectively. 19/21 and 14/15 pts with ctDNA detected at baseline and the postoperative visit relapsed. Detection of ctDNA predicted patients at high risk of relapse at baseline (RFS hazard ratio [HR] 4.7; 95% confidence interval [CI] 2.3-9.6; p < 0.0001) and postoperatively (HR 9.3; 95% CI 4-22; p < 0.0001). Inferior distant metastasis-free survival (DMFS) was associated with ctDNA detection at baseline (HR 5.3; 95% CI 2.5-11; P < 0.0001) and postoperatively (HR 14; 95% CI 5.4-37; P < 0.0001). These findings were validated in an independent cohort. Postoperative ctDNA detection remained an independent predictor of both RFS (HR 8; 95% CI 3-20; P < 0.0001) and DMFS (HR 11; 95% CI 4-30; P < 0.0001) after adjustment for disease stage and BRAF mutation status. In 20/112 pts who received adjuvant therapy, 3/18 pts with a postoperative plasma sample had detectable ctDNA. Serial plasma samples were available in 2 of 3 cases and showed clearance of ctDNA post immunotherapy. At a median follow-up of 7 months, none of the pts with detectable ctDNA who received adjuvant therapy have relapsed.

Conclusions

Detection of ctDNA at baseline and after surgical resection in two independent prospective cohorts identifies pts with stage II/III melanoma at highest risk of relapse with potential to guide adjuvant therapy decisions.

Legal entity responsible for the study

Peter MacCallum Cancer Centre.

Funding

National Health and Medical Research Council, Cancer Research UK, Wellcome Trust.

Disclosure

S.K. Sandhu: Honorarium: Merck, Bristol-Myers Squibb. M. Shackleton: Travel support: BMS, Merck; Consultancy: BMS, Merck, MSD; Honoraria: BMS, Merck, MSD Research support: BMS. A. Haydon: Advisory board: Novartis, MSD. D. Gyorki: Advisory board: Amgen; Honorarium: Amgen. P. Lorigan: Consultancy/ Advisory work: Amgen, GSK, Roche, BMS, Merck, Novartis; Speaker bureau: Merck, BMS, Novartis, Roche; Support for travel: Merck, BMS, Roche. R. Marais: Research funding: Basilea Pharmaceuticals. All other authors have declared no conflicts of interest.

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Proffered paper session - Translational research Proffered Paper session

1830O - Liquid biopsy as tool to monitor and predict clinical benefit from chemotherapy (CT) and immunotherapy (IT) in advanced Non-small cell lung cancer (aNSCLC): a prospective study.

Presentation Number
1830O
Lecture Time
10:18 - 10:30
Speakers
  • Laura Bonanno (Padova, IT)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
20.10.2018
Time
09:15 - 10:45

Abstract

Background

Detecting tumor-specific genetic alterations in plasma has the potential to monitor biological effects of treatment. Aim of the study is to validate the method in EGFR-ALK-ROS1 wild-type (wt) aNSCLC and explore the correlation of variation of mutations in plasma with outcome.

Methods

aNSCLC patients (pts) undergoing systemic anti-cancer treatment were prospectively enrolled in mono-institutional trial MAGIC-1. Tumor DNA was screened through Mass Array (Sequenom) or Next-generation sequencing (NGS). Plasma samples were collected at baseline (T1), after the first cycle of treatment (T2), at first radiological restaging (T3) and at radiological progression (PD) (T4). Plasma DNA was analyzed with Digital droplet PCR (ddPCR) for KRAS-mutated pts (KRAS-m) and NGS for KRAS-wt pts. Semiquantitative index of fractional abundancy (FA) of mutated allele was used.

Results

During 2017 we enrolled 161 pts. Here we depict the KRAS-m cohort (n = 43), including 11 pts treated with IT. At baseline, KRAS mutation (mut) in cfDNA was detected in 21 samples (49%; 95% CI 33.3-64.5). The predictive value of KRAS mut presence in plasma increased from T1 to T3 and was statistically significant for PD (detected in 18 pts) at T3 with an AUC 0.73 (95% CI 0.55-0.91, p-value=0.0132); sensitivity and specificity for PD at cut-off value of 0.013 FA were 58% (95% CI 28-85) and 89% (95% CI 67-99). Any FA reduction (T1-T3) showed an ability to discriminate between groups (non-PD vs PD) of 85% (95% CI: 72-97, p-value<0.0001) with a sensitivity for detection of non-PD of 67% (95% CI 35-90) and a specificity of 89% (95% CI 67-99). Among pts treated with IT, the predictive value of FA reduction (T1-T3) was 86% (95% CI 58-100, p-value=0.0124), with sensitivity of 100% (95% CI 16-100) and specificity of 86% (95% CI 42-100). The only case treated with IT experiencing death within 12 weeks had FA increase from 0 to 10% at T2.

Conclusions

Dynamic variations of KRAS mut in plasma significantly correlate with radiological disease control. Early variation of FA of mutated allele potentially individuates pts experiencing worse outcome during IT. Plasma NGS analyses and expansion cohort in pts treated with IT are ongoing.

Legal entity responsible for the study

Istituto Oncologico Veneto.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Discussion session - Supportive and palliative care 1 Poster Discussion session

1683PD - Factors that influence oncology nutrition efficacy in breast cancer patients under antiestrogenic treatment

Presentation Number
1683PD
Lecture Time
09:30 - 09:30
Speakers
  • Diana V. Artene (Bucharest, RO)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
20.10.2018
Time
09:30 - 10:30

Abstract

Background

Many breast cancer patients gain weight during treatment increasing recurrence, metastasis and mortality risks. The diagnosis overthrows patients’ lifestyle aggravating sedentariness and any pre-existing weight gain causes like insulin and leptin resistance, sleep disturbances and hedonic eating.

Methods

To test the efficacy of an at-home oncology nutrition intervention meant to stop weight gain during antiestrogenic treatment we proposed a diet based on foods naturally high in proteins, omega-3 fatty acids, calcium, probiotics and prebiotics. 331 patients were randomly assigned to the control group, with no oncology nutrition advice besides the physician recommendation to avoid weight gain. 283 patients were randomly assigned to the intervention group and asked to follow the proposed diet. We measured weight and body composition and we compared results at 24 months between intervention and control groups. Then we analysed the results based on the administered oncology treatment type and patients’ age, comorbidities, lifestyle characteristics.

Results

At 24 months, patients within the intervention group reached a modest but statistically significant weight loss and fat loss with no sarcopenia (2.44kg weight loss, 2.37% subcutaneous fat loss, 0.65% visceral fat loss, 1,24% muscle mass increase), while those in the control group maintained weight, increased fat and lost muscle (0.35kg weight loss, 0.34% subcutaneous fat increase, 0.4% visceral fat increase, 0.42 muscle mass decrease). Efficacy was influenced by: age – 31-40 yo patients having worse results than 41-50 yo patients and than 51-80 yo patients; AET type – patients on letrozole having best results; de novo thyroidal disease – lowered fat loss; depression – lowered fat loss; statins – when co-administrated throughout exemestane treatment – lowered fat loss; sleep disturbances – increased sarcopenia. Efficacy was not influenced by: chemotherapy or radiotherapy administration, type of surgery, cardiovascular disease, smoking or by the dieting history.

Conclusions

Oncology nutrition interventions can counteract sarcopenic obesity during antiestrogenic treatment, but the efficacy of the intervention can be influenced by patients’ age and comorbidities.

Legal entity responsible for the study

Carol Davila Medicine University.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Discussion session - Supportive and palliative care 1 Poster Discussion session

1684PD_PR - Physical activity (PA) and patterns of quality of life (QOL) after adjuvant chemotherapy (CT) for breast cancer (BC)

Presentation Number
1684PD_PR
Lecture Time
09:30 - 09:30
Speakers
  • Antonio Di Meglio (Villejuif, FR)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
20.10.2018
Time
09:30 - 10:30

Abstract

Background

We aimed to describe longitudinal patterns of QOL and the interplay between PA and risk of QOL deterioration among BC patients (pts).

Methods

We used a French prospective longitudinal clinical study (CANTO, NCT01993498) to identify 2525 stage I-III BC pts treated with adjuvant CT from 2012-14. PA exposure (GPAQ 16) and QOL (EORTC QLQ C30/B23) were reported by pts before CT, and at 3-6 and 12 months after CT. Pts with levels of PA ≥10 MET-hours/week were considered physically active (as per WHO recommendations on PA). Poor QOL was defined by functional scores <60 and symptoms scores ≥40 (Giesinger, 2016). We used multivariate mixed models to assess patterns of QOL and group based trajectory models to identify clusters of pts with poor QOL and associated risk factors, adjusting for PA as time dependent covariate.

Results

Mean age (Standard Deviation, SD) was 52 y (11). 57%, 62% and 63% pts were physically active before CT, 3-6 and 12 months after CT, respectively. QOL scores before CT were higher among physically active vs inactive pts, including (mean [SD]): global health status (GHS) (69 [1.4] vs 65 [1.4]), physical (90 [1.1] vs 87 [1.1]) and emotional function (65 [1.9] vs 62 [1.9]) (all adjusted p<.05). QOL significantly worsened after CT, but scores remained higher among active pts (p<.001). A cluster of 33% pts had high and persistent risk of poor GHS: associated factors included comorbidities vs no (adjusted odds ratio 1.4 [95% Confidence Interval 1.1-1.9]), low income vs high (1.6 [1.2-2.0]), smoking vs no (1.3 [1.1-1.6]), mastectomy vs partial surgery (1.2 [1.1-1.6]). A significant interaction between recommended levels of PA and risk of poor GHS was observed (p<.001). Consistent with GHS, we found clusters of pts with high risk of poor QOL across physical, emotional and multiple other QOL domains, with similar risk factors and significant interactions with recommended levels of PA.

Conclusions

Among this large cohort of BC survivors, QOL significantly worsened after CT. We were able to group pts following distinct longitudinal patterns of QOL and to identify clinical, socio-economical, and treatment risk factors for poor QOL, including PA behavior. Interventional strategies that also promote PA may help prevent QOL deterioration after CT.

Clinical trial identification

NCT01993498

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Poster Discussion session - Supportive and palliative care 1 Poster Discussion session

1685PD - Effects of 6-month exercise training on quality of life in pancreatic cancer patients: results from a randomized controlled trial

Presentation Number
1685PD
Lecture Time
09:30 - 09:30
Speakers
  • Karen Steindorf (Heidelberg, DE)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
20.10.2018
Time
09:30 - 10:30

Abstract

Background

Given the poor prognosis and high symptom burden of pancreatic cancer, preservation of quality of life (QoL), physical functioning and minimization of adverse treatment effects are important treatment goals in pancreatic cancer patients. Even though exercise has proven to provide health benefits, including improvements in QoL, in patients with various cancer types, studies are rare for more aggressive cancer types like pancreatic cancer. Therefore, we conducted a randomized controlled trial to assess the efficacy of a 6-month resistance training (RT) on QoL in pancreatic cancer patients.

Methods

Sixty-five pancreatic cancer patients, mostly stage IIb after tumor resection and during chemotherapy, were assigned to one of two progressive RT groups (supervised or home-based) or to usual care for 6 months. The primary outcome, the physical functioning subscale of the EORTC QLQ-C30, and other QoL-related outcomes were assessed before the intervention, after 3 and 6 months.

Results

Forty-seven patients (mean age: 60.5 years, 53.2% males) completed the intervention period. After 6 months, no between-group differences were observed. However, after 3 months, intention-to-treat analyses showed significant between-group mean differences (MD) in favor for the pooled RT group for physical functioning (MD = 12.0; p = 0.010), as well as for overall QoL (MD = 12.5; p = 0.014), and several other secondary outcomes (cognitive functioning, insomnia, physical fatigue, and reduced activity). Both modes of delivery, supervised and home-based resistance-training, showed similar effects. Overall mean training adherence rate was 66.5%, with a steady decrease over the 6-month intervention period.

Conclusions

This was the first randomized controlled RT intervention trial in pancreatic cancer patients. The findings showed clinically relevant improvements in QoL after 3 but not 6 months. Given the severity of pancreatic cancer and the importance of maintaining QoL, patients should be timely advised to perform exercise. Future research needs to focus on prolonging the positive mid-term effects, possibly through improving training adherence.

Clinical trial identification

NCT01977066.

Legal entity responsible for the study

German Cancer Research Center.

Funding

German Cancer Aid (Foundation).

Disclosure

All authors have declared no conflicts of interest.

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Poster Discussion session - Supportive and palliative care 1 Poster Discussion session

1513PD - A prospective study examining cachexia predictors in patients with incurable cancer.

Presentation Number
1513PD
Lecture Time
09:30 - 09:30
Speakers
  • Ola Magne Vagnildhaug (Trondheim, NO)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
20.10.2018
Time
09:30 - 10:30

Abstract

Background

A predictive model of cachexia development would help identify those at greatest risk for early therapeutic intervention. The aims of this study were to identify predictors of cachexia development and to use these to create and evaluate the accuracy of a predictive model.

Methods

A secondary analysis of an international, prospective, observational multicentre study was conducted. Patients with incurable cancer and without cachexia, who attended a palliative care unit were amenable to the analysis. Cachexia was defined as weight loss (WL) >5% (6 months) or WL > 2% and body mass index<20kg/m2. Disease related, demographic and patient reported markers were evaluated as possible predictors with Cox analysis. The predictor “cancer type” was divided into high risk (pancreatic or gastric cancer), low risk (sarcoma, breast or hematologic cancer) or neutral risk (all others). A classification and regression tree analysis was used to create a model based on optimal combinations and cut-offs of significant predictors for cachexia development, and accuracy was evaluated with receiver operating characteristic curve analysis.

Results

628 patients, 57% female, were included in the analysis. Median (IQR) age was 65 (17) years and Karnofsky performance status 70 (10). Median (IQR) follow-up was 109 (108) days, and 159 (25%) patients developed cachexia. Initial WL, cancer type, appetite and chronic obstructive pulmonary disease were significant predictors (p ≤ 0.04). A four-level model was created with each level carrying an increasing risk of cachexia development. Level 1-patients (WL < 3%, low risk cancer type and no or little appetite loss) had a relative hazard ratio (RHR) of 0.27 of cachexia development, while level 4-patients (WL 3-5%) had a RHR of 4.9. Accuracy of cachexia predictions at 3 months was 76%, and a risk level ≥3 (1-3% WL and neutral risk cancer type OR < 3% weight loss and high risk cancer type) yielded a sensitivity of 46% and a specificity of 90% of cachexia development.

Conclusions

Important predictors of cachexia have been identified and used to construct a predictive model of cancer cachexia. Patients with a risk level ≥3 have a high risk of cachexia development, and should be targeted for therapeutic intervention.

Legal entity responsible for the study

European Palliative Care Research Centre, NTNU-Norwegian University of Science and Technology.

Funding

The European Palliative Care Research Centre, funded by Helsinn, The Norwegian Cancer Society, Joint Research Council at NTNU.

Disclosure

F. Strasser: Punctual advisorships (boards, expert meetings): Danone, Grünenthal, Helsinn, ISIS Global, Mundipharma, Novartis, Novelpharm, Obexia, Ono Pharmaceutical, Psioxus Therapeutics, PrIME Oncology, Sunstone Captial, Vifor; Unrestricted industry grants for clinical research: Celgene, Fresenius, Helsinn; Participation in a clinical cachexia trial lead by Novartis. All financial support was given to the institution. B. Laird: Honoraria: Helsinn. All other authors have declared no conflicts of interest.

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Poster Discussion session - Supportive and palliative care 1 Poster Discussion session

1514PD - Timing of palliative care referral before and after a cluster randomized controlled trial (RCT) of early palliative care

Presentation Number
1514PD
Lecture Time
10:00 - 10:00
Speakers
  • David Hausner (Toronto, CA)
Location
Hall B3 - Room 21, ICM München, Munich, Germany
Date
20.10.2018
Time
09:30 - 10:30

Abstract

Background

Between December 2006 and February 2011, our cancer center undertook an RCT of early palliative care in patients with lung, gastrointestinal (GI), genitourinary (GU), breast, and gynecological (Gyne) cancers. The trial showed benefits in quality of life favoring early palliative care (at clinical prognosis 6-24 months) over standard care. We hypothesized that there would be an increase in earlier referrals to the oncology palliative care clinic (OPCC) following the RCT.

Methods

Administrative databases were reviewed for 2 groups of patients: Group 1 (before RCT) was seen in the OPCC June-October 2006; Group 2 (following RCT) seen May 2015 - April 2016. Death dates were retrieved in January 2018. Data have been collected for 337/407 patients in Group 1 and 387/1007 in Group 2. Timing of referral was categorized as early (>6 months from referral to death) and late (≤6 months from referral to death). Using chi-square tests for categorical predictors and t-tests for continuous predictors, we compared distributions and means between groups 1 and 2 for demographics, primary tumor site, referring service and referral reason (pain & symptom management [PSM], palliative planning [PP], PSM together with PP [PSM+PP], other).

Results

Early referrals to OPCC increased from 105/337 (31%) to 180/387 (47%) (p < 0.001). For women, early referrals increased from 33% to 51%, and for men from 30% to 42%. Although there was no change in the timeliness of referrals for PSM alone, earlier referrals increased significantly among patients referred for PSM+PP, and those referred for PP. Early referrals increased among medical oncologists from 32% (65/206) to 48% (118/244) (p < 0.001) but not among radiation oncologists (29% [23/80] to 40% [28/70], p = 0.17). Early referrals tended to increase for all tumor site groups except head and neck, with significant increases among patients with GI cancers (25% [22/87] to 48% [50/104], p = 0.001), and Gyne cancers (23% [8/35] to 58% [32/55], p = 0.001).

Conclusions

Following an RCT supporting early palliative care for patients with advanced cancer, oncologists referred patients substantially earlier to an outpatient palliative care clinic.

Legal entity responsible for the study

Camilla Zimmermann.

Funding

Canadian Institutes of Health Research.

Disclosure

All authors have declared no conflicts of interest.

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