- Julien Taieb (Paris, France)
80MO - Gut microbiome analysis for predicting neoadjuvant chemoradiotherapy response in locally advanced rectal cancer patients (ID 429)
- Yuxi Yi (Shanghai, China)
Abstract
Background
The gut microbiome has been reported to be involved in antitumour immunotherapy and chemotherapy responses; however, evidence-based research on the role of the gut microbiome in neoadjuvant chemoradiotherapy (nCRT) responses of locally advanced rectal cancer (LARC) patients is scarce. This research aims to evaluate the feasibility of the gut microbiome in predicting nCRT responses in LARC patients.
Methods
We collected 167 faecal samples from 84 LARC patients before and after nCRT in our institution and 31 faecal samples from healthy individuals for 16S ribosomal RNA sequencing. We used the AJCC tumour regression grade (TRG) system to evaluate the nCRT responses and accordingly divided patients into two groups. Patients with TRG scores of 0-1 were grouped as responders (R group), and those with TRG scores of 2-3 were grouped as non-responders (NR group). After characterizing the gut microbiome and identifying biomarker bacteria related to nCRT responses, we constructed a random forest classifier for nCRT response prediction of a training set of 37 baseline samples and validated the classifier with the remaining 47 baseline samples.
Results
Taxonomic differences in relation to nCRT responses were noticed in baseline faecal samples, including overrepresentation of butyrate-producing bacteria (Dorea and Anaerostipes) in R, and overrepresentation of Coriobacteriaceae and Fusobacterium in NR. During nCRT, a decline in bacterial richness related to therapeutic responses was observed. Furthermore, microbiome alterations imposed by nCRT were represented by a decrease in LARC-related pathogens and an increase in Lactobacillus and Streptococcus, and the increase of Streptococcus was exclusively shown in R subgroup. Ten variables were selected for the classifier, including Dorea, Anaerostipes and Streptococcus, and the area under the curve reached 93.57% (95% CI: 85.76%∼100.00%) in the training set and 73.53% (95% CI: 58.96%∼88.11%) in the validation set.
Conclusions
The gut microbiome plays a role in nCRT responses and provides potential biomarkers to predict nCRT responses. Further validation in a larger sample size is needed.
Legal entity responsible for the study
Fudan University Shanghai Cancer Center.
Funding
the National Natural Science Foundation of China.
Disclosure
All authors have declared no conflicts of interest.
81MO - Clinical experience of a personalized and tumour-informed circulating tumour DNA assay for minimal residual disease detection in oligometastatic colorectal cancer patients (ID 459)
- Stacey A. Cohen (Seattle, WA, United States of America)
Abstract
Background
For patients with oligometastatic colorectal cancer (CRC) treated with definitive management with curative intent, >50% still recur post-resection. Circulating tumor DNA (ctDNA) testing can be used to assess minimal residual disease (MRD) in these patients and predict the risk of recurrence. Prospective evaluation of this methodology in clinical practice has been limited to date and the use of adjuvant chemotherapy (ACT) after metastasectomy is based on data extrapolated from earlier stage CRC.
Methods
A personalized and tumor-informed multiplex PCR assay (Signatera™ bespoke mPCR NGS assay) was used for the detection and quantification of ctDNA for MRD assessment. We present results from an ongoing early adopter program of ctDNA testing in patients with oligometastatic CRC (largely isolated to the liver) treated with surgery, radiation, or other definitive metastasis therapy. ACT was given at the discretion of the treating physician.
Results
ctDNA levels were analyzed in 93 oligometastatic CRC patients, post-resection/ablation (range 3 – 150 days, median 52 days). In the pre-surgical setting, ctDNA was detected in 100% (9/9) of the patients. Post-treatment MRD was detected in 49% (26/53) of patients, with an average of 454.15 mean tumor molecules/mL (range 0.11 - 13,274 MTM/mL, median 5.61 MTM/mL). MRD rates in patients post-oligometastatic therapy were found to be higher than in historical non-metastatic patients who had the same assay post-surgery (49% vs 18%). Longitudinal case studies describing the ctDNA clearance effects of ACT on MRD rates in the post-metastasectomy setting will be presented.
Conclusions
This is the largest set of clinical experience data analyzing ctDNA in oligometastatic CRC patients and shows definitive evidence that a highly sensitive MRD assay can detect residual disease after curative intent procedures. An average MRD rate of 49% is consistent with published relapse rates of ∼50% post-oligometastatic resection, suggesting this assay accurately measures residual disease and may be prognostic for relapse, as well as potentially predictive for who might benefit from post-metastasectomy ACT.
Clinical trial identification
NA
Editorial acknowledgement
Editorial support was provided by Meenaksh Malhotra, Ph.D. from Natera, Inc.
Legal entity responsible for the study
The authors.
Funding
Natera, Inc.
Disclosure
S.A. Cohen: Advisory/Consultancy: Natera, Inc.; Research grant/Funding (self): Boston Medical Polaris; Research grant/Funding (self): Isofol. N. Hook, S. Krinshpun, L. Westbrook, K. Loranger, J. Wallace, S. Sharma: Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc. A. Aleshin: Leadership role, Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc.; Advisory/Consultancy: Mission Bio; Advisory/Consultancy: Notable Labs. P. Billings: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc.; Advisory/Consultancy: Mission Bio.
82MO - Automatical risk stratifying for colorectal cancer by deep learning based pathological score (ID 628)
- Shenlun Chen (Shanghai, China)
Abstract
Background
Histology whole-slide images contains crucial information of patients' risk. In this study, we aimed to develop a fully automated approach for stratifying colorectal cancer (CRC) patients’ risk of mortality by applying deep learning convolutional neural networks to histology whole-slide images.
Methods
We developed deep learning model of two-stage for stratifying CRC's survival risk. First a tumor differentiation classifier was trained on expert annotations to generate probability maps and a predictor index for tumor differentiation. Survival times and aforementioned maps were used to train a Cox neural network that predicts overall survival. Three CRC datasets were used including 2 public datasets from The Cancer Genome Atlas (TCGA); TCGA-COAD was used for model training, TCGA-READ and a local institutional dataset were used for validation.
Results
The accuracy of predicting tumor differentiation achieved to 85% (AUCs 0.983, 0.963, 0.963 and 0.981 for low, medium, high grades, and normal tissue, respectively) in validation set of TCGA-COAD. The patient specific score that predicted by Cox survival CNN networks showed it;s moderate discrimination ability with c-index of 0.65 in validation set. The score can also be combined with clinical factors (age, gender and TNM staging) as a powerful prediction model to stratify CCR's risk. The combined Cox model archieved c-indices of 0.77 and 0.79 in two independent validation sets. C-indices of the model in two validation sets were 0.72 and 0.75 without deep learning based pathological score.
Conclusions
In this study, we proved that the deep learning based psthological scores were added factor beyongd normal clinical factors of sex, age and TNM staging and significantly enhanced the prediction performance of these factors. This study demonstrates that deep learning can provide a meaningful reference for tumor differentiation grading and patient risk evaluation for pathologists.
Legal entity responsible for the study
Fudan University Shanghai Cancer Center.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Invited Discussant abstracts 80MO, 81MO and 82MO (ID 1089)
- Dawn Qing Qing Chong (Singapore, Singapore)
LIVE Q&A (ID 1090)
- Julien Taieb (Paris, France)
83MO - AMG 510, a novel small molecule inhibitor of KRAS(G12C), for patients (pts) with advanced gastrointestinal (GI) cancers: Results from the CodeBreaK100 phase I trial (ID 513)
- Timothy J. Price (Woodville, SA, Australia)
Abstract
Background
KRAS p.G12C mutation occurs in 1-3% of GI cancers. AMG 510 is a first-in-class small molecule inhibitor of KRASG12C. Previously, AMG 510 demonstrated a favorable safety profile and preliminary efficacy in the phase I, first-in-human trial involving pts with advanced solid tumors harboring KRAS p.G12C. Here, we present updated data in a subset of pts with advanced colorectal cancer (CRC) or other GI cancers.
Methods
Key inclusion criteria: KRAS p.G12C identified by molecular testing and prior systemic anticancer therapy. Primary endpoint was safety. Key secondary endpoints: objective response rate (ORR) and disease control rate (DCR), as per RECIST 1.1. Oral daily doses of 180, 360, 720, and 960mg were tested in dose escalation, and 960mg was selected for expansion.
Results
As of Jan 8, 2020, 59 pts (25 [42.4%] female, median age 58 [range: 33–82]), including 42 with CRC and 17 with other GI cancers, were enrolled. Pts received a median of 3 (range: 1–4) prior lines of therapy, with 24 (40.7%) receiving > 3 prior lines. Median follow-up was 7.7 (range: 1.2–15.9) months. 17 (28.8%) died, and 16 (27.1%) remained on treatment (tx). 28 (47.5%) and 10 (16.9%) pts had remained on tx for ≥ 3 and 6 months, respectively. Tx-related adverse events (TRAEs) occurred in 27 pts (45.8%); most were grade 1/2. 3 (5.1%) had grade 3 TRAEs, including diarrhea (3.4%) and anemia (1.7%). No dose-limiting toxicities, fatal / grade >3 TRAEs, or TRAEs leading to discontinuation were reported. All 42 pts with CRC had been followed up by ≥ 7 weeks and were evaluable for response. ORR and DCR were 7.1% (all confirmed) and 76.2%, respectively. At 960mg, ORR and DCR were 12.0% (3/25) and 80.0% (20/25). 15 of 17 pts with other GI cancers were evaluable: 1 confirmed partial response (appendiceal), 9 stable disease (6 pancreatic, 2 appendiceal, and 1 bile duct), and 5 progressive disease. 3 pts with pancreatic cancer achieving stable disease had the best tumor burden reduction of 28.0%, 28.9%, and 31.6% from baseline, respectively.
Conclusions
In pts with heavily pretreated KRAS p.G12C mutant GI cancers, AMG 510 was well tolerated, with the majority of pts achieving disease control. Study is ongoing (NCT03600883).
Clinical trial identification
NCT03600883.
Editorial acknowledgement
Yang Li, PhD (Amgen Inc.) provided medical writing assistance.
Legal entity responsible for the study
Amgen Inc.
Funding
Amgen Inc.
Disclosure
J.H. Strickler: Advisory/Consultancy, Research grant/Funding (institution): Amgen; Bayer; Seattle Genetics; OncoMed; Genentech/Roche; Research grant/Funding (institution): AbbVie; Exelixis; Gilead Sciences; Macrogenics; MedImmune; Nektar Therapeutics; Advisory/Consultancy: Celgene; Chengdu Kanghong Biotechnology; Chugai. M. Fakih: Research grant/Funding (institution): AstraZeneca; Amgen; Novartis; Advisory/Consultancy: Array; Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen; Advisory/Consultancy: Seattle Genetics. T.J. Price: Research grant/Funding (institution): Amgen. J. Desai: Advisory/Consultancy: Amgen; Advisory/Consultancy: BeiGene; Advisory/Consultancy, Research grant/Funding (institution): Bionomics; Advisory/Consultancy: Eisai; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Roche. G. Durm: Research grant/Funding (institution): Merck; BMS; AstraZeneca. J.C. Krauss: Research grant/Funding (institution): Amgen; NSABP Foundation; AbbVie; Boehringer Ingelheim; Boston Biomedical; Oncomed Pharmaceuticals; Ignyta/Roche; Baxalta; Pfizer; Isofol. Y. Kuboki: Research grant/Funding (institution): Amgen; Takeda; AstraZeneca; Ono Pharmaceutical Company Limited; Taiho Pharmaceutical Company Limited; Daiichi-sankyo Company Limited; Boehringer Ingelheim GmbH; Honoraria (self): Takeda; Taiho; MSD; Sanofi; Bayer Yakuhin; Eli Lilly Japan. A. Sacher: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca/MedImmune; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Kisoji; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech/Roche; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy: Amgen; Travel/Accommodation/Expenses: Gritstone Oncology; Travel/Accommodation/Expenses: GSK; Honoraria (self): Tesaro. H. Henary; J. Kim: Shareholder/Stockholder/Stock options, Full/Part-time employment: Amgen. D.S. Hong: Shareholder/Stockholder/Stock options: MolecularMatch; Oncorena; Presagia; Honoraria (self), Advisory/Consultancy: Adaptimmune; Baxter; Bayer; Merrimack; Advisory/Consultancy: Alpha Insights; Axiom Biotechnologies; Eisai; Genentech; GLG; GroupH; Guidepoint Global; Janssen; Medscape; Numab; Pfizer; Seattle Genetics; Advisory/Consultancy, Additional disclosures: advisory - Trieza Therapeutics. Research Funding: AbbVie; Adaptimmune; Amgen; Amgen; AstraZeneca; Bayer; Bristol-Myers Squibb; Daiichi Sankyo; Eisai; Fate Therapeutics; Genentech; Genmab; Ignyta; Infinity Pharmaceuticals; Kite Pharma; Kyowa Hakko Kirin; Lilly; Loxo; MedImmune; Merck; Mirati Therapeutics; miRNA Therapeutics; Molecular Templates; Mologen; NCI-CTEP; Novartis; Pfizer; Seattle Genetics; Takeda Travel, Accommodations, Expenses: Genmab; Loxo; miRNA Therapeutics: Takeda. All other authors have declared no conflicts of interest.
84MO - A phase II, multicenter, open-label study of trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-expressing metastatic colorectal cancer (mCRC): DESTINY-CRC01 (ID 296)
- Takayuki Yoshino (Kashiwa, Chiba, Japan)
Abstract
Background
T-DXd is an antibody-drug conjugate composed of an anti-HER2 antibody and topoisomerase I inhibitor payload. Early studies have shown promising activity in advanced HER2-expressing tumors. DESTINY-CRC01 (NCT03384940) is a phase II, open-label, multicenter study of T-DXd in HER2-expressing mCRC.
Methods
Patients (pts) with centrally confirmed HER2-expressing, RAS-wild type mCRC that progressed on ≥ 2 prior regimens received T-DXd 6.4 mg/kg every 3 weeks (q3w) in 3 cohorts (A: HER2 IHC 3+ or IHC 2+/ISH+; B: IHC 2+/ISH−; C: IHC 1+). The primary endpoint was confirmed objective response rate (ORR) by independent central review in cohort A; secondary endpoints included, disease control rate (DCR; CR + PR + SD), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and ORR in cohorts B and C.
Results
At data cutoff (Aug 9, 2019), 78 pts (A, 53; B, 7; C, 18) had received T-DXd. Median age was 58.5 y, 52.6% of pts were male, and 89.7% had left colon or rectum cancer; median number of prior regimens was 4; all pts had prior irinotecan. Median treatment duration was 3.5 mo; 38.5% of pts remained on T-DXd treatment. The confirmed ORR was 45.3% (24/53 pts; 95% CI, 31.6-59.6%) in cohort A, including 1 CR and 23 PRs; median DOR was not reached. The ORR in pts with prior anti-HER2 treatment was 43.8% (7/16 pts; 95% CI, 19.8-70.1%). The DCR was 83.0% (44/53 pts; 95% CI, 70.2-91.9%); median PFS was 6.9 mo (95% CI, 4.1 mo-NE); median OS was not reached. No responses were observed in cohort B or C. Grade ≥ 3 treatment-emergent adverse events (TEAEs) occurred in 61.5% of 78 pts; the most common (≥10%) were neutrophil count decreased (21.8%) and anemia (14.1%). Seven pts (9.0%) had TEAEs leading to drug discontinuation. Five pts (6.4%) had interstitial lung disease (ILD) adjudicated by an independent committee as related to T-DXd (2 grade 2; 1 grade 3; 2 grade 5 [the only drug related deaths]).
Conclusions
T-DXd demonstrated remarkable activity in pts with HER2-expressing mCRC refractory to standard therapies, with a safety profile consistent with previous results. ILD is an important risk and requires careful recognition and intervention.
Clinical trial identification
NCT03384940.
Legal entity responsible for the study
Daiichi Sankyo Co., Ltd.
Funding
Daiichi Sankyo Co., Ltd.
Disclosure
T. Yoshino: Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical Co., Ltd.; Chugai Pharmaceutical Co., Ltd.; Eli Lilly Japan K.K.; Bayer Yakuhin, Ltd.; Merck Biopharma Co., Ltd.; Takeda Pharmaceutical Company Limited; Research grant/Funding (institution): MSD K.K.; Ono Pharmaceutical Co., Ltd.; Daiichi Sankyo Co., Ltd.; Sumitomo Dainippon Pharma Co., Ltd; Parexel International Inc.; Sanofi K.K.; Amgen K.K. S. Siena: Advisory/Consultancy, Travel/Accommodation/Expenses, Licensing/Royalties: Amgen; Advisory/Consultancy: Roche/Genetech; Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy: Bristol-Myers Squibb; Clovis Oncology; Daiichi Sankyo; Incyte; Merck; Novartis; Seattle Genetics; CheckmAb; Research grant/Funding (institution): MSD Oncology; Travel/Accommodation/Expenses: Roche; Shareholder/Stockholder/Stock options: Guardant Health; Shareholder/Stockholder/Stock options: Myriad Genetics. M. Di Bartolomeo: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Eli Lilly SpA; Honoraria (self), Speaker Bureau/Expert testimony: MSD; Honoraria (self): Merck Serono; Honoraria (self): Servier; Travel/Accommodation/Expenses: Roche. K. Raghav: Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: AstraZeneca. T. Masuishi: Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Merck Serono; Honoraria (self): Chugai Pharma; Honoraria (self): Yakult ; Honoraria (self): Takeda; Honoraria (self): Eli Lilly; Honoraria (self): Bayer Yakuhin; Honoraria (self): Sanofi; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Ono Pharmaceutical. F. Loupakis: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bayer; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Serono. H. Kawakami: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Ono Pharmaceutical; Honoraria (self), Advisory/Consultancy: Eli Lilly Japan; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Taiho; Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self): Takeda; Honoraria (self), Advisory/Consultancy: MSD KK; Research grant/Funding (institution): Eisai. K. Yamaguchi: Honoraria (institution): Daiichi Sankyo; Honoraria (institution): Taiho Pharmaceutical; Honoraria (institution): Chugai Pharma; Honoraria (institution): Ono Pharmaceutical; Honoraria (institution): Eli Lilly; Honoraria (institution): Sanofi; Honoraria (institution): MSD; Honoraria (institution): Sumitomo Dainippon Pharma; Honoraria (institution): Gilead Sciences; Honoraria (institution): Boehringer Ingelheim; Honoraria (institution): Eisai; Honoraria (institution): Yakult; Speaker Bureau/Expert testimony: Bristol-Myers Squibb Japan; Speaker Bureau/Expert testimony: Takeda. T. Nishina: Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Chugai Pharma; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Honoraria (self), Research grant/Funding (institution): Merck Serono; Honoraria (self): Takeda; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Nihonkayaku; Research grant/Funding (institution): Sumitomo Dainippon Pharma; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Ono Pharmaceutical. M. Fakih: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Amgen; Advisory/Consultancy: Array BioPharma; Advisory/Consultancy: Bayer; Advisory/Consultancy: Pfizer; Speaker Bureau/Expert testimony: Guardant360; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): AstraZeneca. E. Elez: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: F. Hoffman-La Roche; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Servier; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Amgen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Serono; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Array Biopharma; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi; Honoraria (institution): MSD; AbbVie; GSK; AstraZeneca; Novartis; Boehringer Ingelheim. F. Ciardiello: Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Pierre; Research grant/Funding (institution): Ipsen. K. Saxena; E. Yamamoto; K. Kobayashi; E. Bako; Y. Okuda: Full/Part-time employment, employee: Daiichi Sankyo. A. Grothey: Honoraria (self): Elsevier; Aptitude Health; Imedex; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Boston Biomedical; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Research grant/Funding (institution): Array BioPharma; Advisory/Consultancy: Guardant Health; Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Eisai; Travel/Accommodation/Expenses: Boehringer Ingelheim; Travel/Accommodation/Expenses: Merck Sharp & Dohme. All other authors have declared no conflicts of interest.
85MO - Management of adverse events associated with encorafenib plus cetuximab in patients with BRAF V600E mutant metastatic colorectal cancer (BEACON CRC Study) (ID 601)
- Chang-Fang Chiu (Taichung City, Taiwan)
Abstract
Background
BRAF mutations occur in up to 15% of patients with metastatic colorectal cancer (mCRC),the BRAF V600E mutation is a marker of poor prognosis. In BEACON CRC study,triplet therapy encorafenib + binimetinib + cetuximab and doublet therapy with encorafenib + cetuximab demonstrated improved overall survival (OS) and objective response in patients with BRAF V600E mCRC compared with current standard of care (median OS: 9.3 months (m) [triplet] and 9.3 m [doublet] vs 5.9 m [control]; ORR:27% [triplet] 20% [doublet] vs 2% [control], p<0.0001 for both). Here, we focus on common adverse events (AEs) that occurred during the study with the doublet regimen, and best practices on managing and mitigating these events.
Methods
BEACON CRC is a randomized, 3-arm, Ph 3 study evaluating triplet (n=224) or doublet (n=220) regimens vs investigator’s choice of irinotecan or FOLFIRI + cetuximab (n=221) in patients (pts) with BRAF V600E-mutated mCRC. Incidence and severity of AEs were assessed according to the NCICTCAE, version 4.03.
Results
In the doublet arm, the most common any grade AEs were diarrhea (38%), nausea (38%), fatigue (33%), decreased appetite (31%). The most common skin-related any grade AEs were dermatitis acneiform (30%), rash (15%), dry skin (13%), pruritus (11%). Grade ≥3 AEs occurred in 57% of pts (vs 64% in the control arm) and the most common were anemia (6%), intestinal obstruction (5%), fatigue (4%), asthenia (4%), abdominal pain (3%). Common laboratory abnormalities included low hemoglobin (any grade: 39%, grade 3–4: 6%) and high creatinine (any grade: 54%, grade 3–4: 3%). Any grade arthralgia and myalgia, associated with BRAF inhibitors, occurred in 23% and 15% of pts, and led to dose reductions of either study drug in <1% of pts; no pts discontinued either drug. Discontinuation of any study drug primarily due to an AE occurred in 12% of patients (vs 17% in the control arm). Management of AEs with the doublet regimen and management of class-based AEs will be described.
Conclusions
AEs that occurred with encorafenib + cetuximab during the BEACON CRC study were generally manageable, reversible, and infrequently associated with treatment discontinuation.
Clinical trial identification
NCT02928224.
Editorial acknowledgement
Writing and editorial assistance were provided by Namiko Abe, PhD, of Caudex, funded by Pfizer.
Legal entity responsible for the study
Pfizer.
Funding
Pfizer.
Disclosure
C-F. Chiu: Research grant/Funding (institution): Array Biopharma; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): F. Hoffmann-La Roche Ltd; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Ono; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Janssen-Cilag SA. Y-M. Yeh: Research grant/Funding (institution): Pfizer. K-H. Yeh: Research grant/Funding (institution): Pfizer. J. Desai: Advisory/Consultancy: Eli Lilly; Eisai; BeiGene; Biocon; Amgen; Research grant/Funding (institution): Roche; GSK; Novartis; Bionomics; BeiGene; Eli Lilly; BMS; AstraZeneca; MedImmune. T.J. Price: Research grant/Funding (institution): Amgen; Advisory/Consultancy: MSD; Advisory/Consultancy: Amgen. N. Tebbutt: Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Merck Serono. J. Tabernero: Honoraria (self), Advisory/Consultancy: Array Biopharma; AstraZeneca; Bayer; BeiGene; Roche Diagnostics; Boehringer Ingelheim; Chugai; F. Hoffmann-La Roche Ltd.; Merck Serono; Genentech, Inc.; Genmab A/S; HalioDX SAS; Halozyme; Imugene Limited; Inflection Biosciences Limited; Ipsen; Kura Oncology; Lilly; MSD; Menarini; VCN Biosciences. A. Grothey: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Full/Part-time employment: Array BioPharma; Research grant/Funding (self): Novartis; Research grant/Funding (self): Boehringer Ingelheim. R. Yaeger: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Full/Part-time employment: Array BioPharma; Research grant/Funding (self): Novartis; Research grant/Funding (self): Boehringer Ingelheim. A. Gollerkeri: Full/Part-time employment: Pfizer. K. Maharry: Full/Part-time employment: Pfizer. S. Kopetz: Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Merck; Advisory/Consultancy: Karyopharma Therapeutics; Advisory/Consultancy: Amal Therapeutics; Advisory/Consultancy: Navire Pharma; Advisory/Consultancy: Symphogen; Advisory/Consultancy: Holy Stone; Advisory/Consultancy: Amgen; Advisory/Consultancy: Novartis; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Boston Biomedical; Advisory/Consultancy: AstraZeneca/MedImmune; Advisory/Consultancy: Bayer Healthcare; Advisory/Consultancy: Pierre-Fabre. All other authors have declared no conflicts of interest.
Invited Discussant abstracts 83MO, 84MO and 85MO (ID 1091)
- Julien Taieb (Paris, France)
LIVE Q&A (ID 1092)
- Julien Taieb (Paris, France)