- Email: [email protected]
Impact of concomitant medications on disease free survival (DFS) and overall survival (OS) in patients from the PETACC8 study
abstracts
Annals of Oncology Results:
Table: 546P Univariate and multivariate analysis
locally
0.376 0.037 0.075 0.356 0.152 0.102 0.121 0.008
1.409 0.969 0.634 1.179 1.1 1.28 1.42 3.4
0.657 – 3.02 0.940 – 0.998 0.382 – 1.052 0.697 – 2.02 0.646 – 1.92 0.947 – 1.75 0.906 – 2.23 1.26 – 9.6
0.378 0.039 0.078 0.550 0.697 0.106 0.126 0.016
In the Kaplan and meier analysis, recurrence free survival (SLR) was P ¼ 0.03. Independent factors for recurrence were age and ECOG (95% CI 0.940 – 0.998¸ P ¼ 0.037, HR 3.4 95% IC 1.26 – 9.6, P ¼ 0.016). Our findings showed a better SLR in the low dINP subgroup, so we took it as a cutoff 5. Patients who presented a dINP less than 5, have a better SLR in relation to those who have a dINP > 5. P ¼ 0.013. Conclusions: The difference less than 5 between the nutritional index before and after neoadjuvant chemoradiotherapy in patients with locally advanced adenocarcinoma of the rectum is associated with an increase in SLR as an independent predictor of recurrence. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
547P
Short-term clinical outcomes of robotic-assisted total mesorectal excision in rectal cancer after concurrent chemoradiotherapy
P. Chen1, J-Y. Wang2 1 General Surgery, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan, 2 Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan Background: To evaluate the short-term oncological outcomes of robotic-assisted total mesorectal excision (TME) in patients with rectal cancer after neoadjuvant CCRT (concurrent chemoradiotherapy). Methods: We enrolled 120 patients with stages I-IV rectal cancer who underwent robotic-assisted total mesorectal excision (TME) after neoadjuvant concurrent chemoradiotherapy at a single institution between July 2013 and November 2017. Results: Of the 120 patients enrolled, all of them underwent preoperative concurrent chemoradiotherapy. Furthermore, among these 120 patients, 34 (28.3%) achieved a pathologic complete response and 19 people had local or distant recurrences. In a median follow up of 24 months, the 2-year disease-free survival(DFS) and overall survival(OS) were and 84% and 86%. Conclusions: The results demonstrate that robotic-assisted TME for patients with rectal cancer after neoadjuvant CCRT (concurrent chemoradiotherapy) is effective and for patient with tumor invaded to bladder, prostate or uterus, neoadjuvant chemotherapy is a safe and effective way for organ-preserving instead of salvage surgery. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
548P
Local immune status in cancer cell nests can be a predictor of survival for rectal cancer with neoadjuvant radiotherapy
549P
Impact of concomitant medications on disease free survival (DFS) and overall survival (OS) in patients from the PETACC8 study
B. Cle´mence1, J. Taieb2, M. Boulin3, K. Le Malicot4, L.M. Dourthe5, B. Avisse6, P. Laplaige7, C. Borel8, D. Arsene9, F. Kikolski10, B. Denis11, P. Geoffroy12, R. Coriat13, G. Piot14, C. Lepage1 1 Hepatogastroenterology Department, CHU Dijon, Dijon, France, 2Department of Gastroenterology and Digestive Oncology, Hopital European George Pompidou, Paris, France, 3Pharmacy Department, CHU Dijon, Dijon, France, 4Biostatistics, FFCD, Dijon, France, 5Oncology Department, Clinique Sainte Anne, Strasbourg, France, 6 Hepatogastroenterology Department, Centre Hospitalier Pierre Oudot, BourgoinJallieu, France, 7Medical Oncology Department, Polyclinique de Blois, La Chaussee St. Victor, France, 8Medical Oncology Department, Centre Paul Strauss Centre de Lutte Contre le Cancer, Strasbourg, France, 9Oncology Department, CHU de Caen, Caen, France, 10Gastroenterology and Hepatology, Hoˆpital Robert Boulin, Libourne, France, 11 Hepatogastroenterology Department, Hoˆpital Louis Pasteur, Colmar, France, 12 Hepatogastroenterology Department, Clinique Saint-Vincent, Epernay, France, 13 Gastroenterology Department and Digestive Oncology, Hoˆpital Cochin, Paris, France, 14 Oncology Department, Clinique des Ormeaux, Le Havre, France Background: Impact of comedications and comorbidities upon OS isn’t well described in cancer patients (pts). We aimed to evaluate their impacts on DFS and OS on pts resected from a stage III colon cancer and treated by adjuvant FOLFOX-4 þ/- cetuximab in the PETACC8 study. Methods: Treatments (trts) categories were defined according to the WHO ATC classification system. We focused on 4 medication classes: anticoagulant, cardiovascular, antidiarrheal and antidiabetic trts. We classified the 2559 pts in each category if they took trt at baseline or during study whatever the duration was. Kaplan-Meier method and Cox model were used to compare survival curves. Multivariate analyses were performed on the overall population and according to trt arm. Results: Only 1% of pts had no comedications. Comedications with anticoagulant, cardiovascular, antidiarrheal and antidiabetic trts were observed respectively in 18%, 40%, 30% and 9% of the cases. Patients with antidiabetic or cardiovascular trts had more comorbidities. For each other comedication categories, baseline characteristics were balanced between pts treated or not. All comedication categories, except antidiarrheals, were associated with a significant decrease of DFS and OS (Table). Dose-intensity was balanced and may not explain survival differences. For pts treated with at least one cardiac, diabetic or anticoagulant trts, severe events were more frequently reported, including 9 early deaths. The use of antidiarrheals is maybe associated to a better exposure to chemotherapy as reflected by a higher rate of grade 3 adverse events but also a potential better efficacy. Table. Comedications impact on DFS and OS.
X. Lin1, F. Lin2, Q. Zhuang2, X. Zhang2, Y. Huang2, L. Tang2, J. Li3, W. Junxin1 1 Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China, 2Radiation Oncology, Fujian Medical University Cancer Hospital, Fuzhou, China, 3Radiation, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China
Volume 30 | Supplement 5 | October 2019
doi:10.1093/annonc/mdz246 | v207
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Gender Age body mass index Degree Differentiation ypT ypN Diferencial INP ECOG
Background: Although neoadjuvant chemoradiotherapy is the standard treatment for advanced rectal cancer (LARC), it remains difficult to predict the prognosis of LARC patients. We aimed to explore the impacts of local immune status on survival of LARC after noeadjuvant radiotherapy (nRT). Methods: A total of 76 consecutive LARC patients were enrolled in our institute from February 2012 to September 2015. CD3þ T-cell and CD8þ T-cell count were determined from surgical specimens. Factors associated with disease-free survival (DFS) and overall survival (OS) were identified by univariate and multivariate Cox regression. SPSS 22.0 was used for statistical analyse. Results: The median follow-up time was 29.0 months (range 2.0-59). The Cutoff Finder software identified an optimal CD3þ T-cell cutoff value of 12.5% and CD8þ Tcell value of 9% for our patients. According to the Kaplan-Meier analysis, CD3þ T-cell 12.5% was significantly related to favorable DFS (P ¼ 0.020), while there was no significant difference between CD3þ T-cell and OS (P ¼ 0.238). Meanwhile, CD8þ T-cell 9% was found to have a positive effect on DFS and OS (P ¼ 0.012 and P ¼ 0.035, respectively). In the multivariate Cox regression model, CD8þ T-cell <9% was independent risk factors for poor DFS (HR ¼ 0.492, 95%CI¼ 0.252-0.960, P ¼ 0.038). Furthermore, CD8þ T-cell (HR ¼ 0.268, 95%CI¼ 0.076-0.941, P ¼ 0.040) and T stage (HR ¼ 0.151, 95%CI¼ 0.030-0.7530, P ¼ 0.021) were independent predictors of OS. Conclusions: High CD8þ T-cell count were significantly related to good survival in LARC patients with nRT. Local immune status was suggested to be measured in order to predict the prognosis of patients with LACR after nRT. Legal entity responsible for the study: Xijin Lin. Funding: The Fujian Province Natural Science Foundation (2017J01260), Joint Funds for the Innovation of Science and Technology, Fujian province (2017Y9074), and the Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing (2017 Open Project-9). Disclosure: All authors have declared no conflicts of interest.
abstracts
Annals of Oncology 551P
Table: 549P Overall analysis
OS
HR [95%CI]
p
HR [95%CI]
p
1.33 [1.10–1.62]
.003
1.34 [1.07–1.67]
.01
0.87 [0.73–1.04]
.12
0.78 [0.63–0.96]
.02
1.20 [1.03–1.41]
.02
1.28 [1.07–1.54]
.01
1.37 [1.07–1.76]
.01
1.45 [1.09–1.92]
.01
Conclusions: Comorbidities related to analyzed ATC classes negatively impact OS and DFS in PETACC8 pts, except antidiarrheal agents which positively impact OS and DFS. Clinical trial identification: PETACC8; 2005-003463-23. Legal entity responsible for the study: Fe´de´ration Francophone de Cance´rologie Digestive, Dijon. Funding: Merck and Sanofi. Disclosure: J. Taieb: Advisory / Consultancy: Merck; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Roche Genentech; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Amgen. All other authors have declared no conflicts of interest.
550P
Updated results of NORDIC 8, a randomised trial of cetuximab every 2 weeks with FOLFIRI or cetuximab with alternating FOLFIRI/FOLFOX in patients with RAS and BRAF wild type metastatic colorectal cancer
P. Pfeiffer1, J.K. Bjerregaard2, C. Qvortrup3, H. Sorbye4, B. Glimelius5, C. Kersten6 1 Experimental Research in Medical Cancer Therapy, Odense University Hospital, Odense, Denmark, 2Department of Oncology, Odense University Hospital, Odense, Denmark, 3Department of Oncology, Finsen Centre - Rigshospitalet, Copenhagen, Denmark, 4Oncology, Haukeland Universitetssykehus, Bergen, Norway, 5Section of Experimental and Clinical Oncology, Department of Immunology, Genetics and Pathology, Uppsala, Sweden, 6Centre for Cancer Treatment, Sorlandet Hospital, Kristiansand, Norway Background: Cetuximab (cet) improves efficacy of first-line FOLFIRI in pts with RAS/ RAFwt metastatic colorectal cancer (mCRC). Triplet chemotherapy improves efficacy further but with increased toxicity. Alternating FOLFIRI/FOLFOX is a different way to administer all 3 cytotoxic drugs. We report the updated results from Nordic 8, a multicentre, randomised trial comparing cet with FOLFIRI (arm A) or with FOLFIRI alternating with FOLFOX (arm B). Methods: In this investigator initiated randomised trial, 173 chemo-naı¨ve mCRC patients received cet with FOLFIRI or cet with FOLFIRI (2 cycles) alternating with FOLFOX until PD. Main inclusion criteria were PS 0 or 1, RASwt and ESMO group 1-3 (prior to April 2014 only ESMO group 1 when 36 patients had been included)). The primary endpoint was RR (increase from 60% to 75%) and secondary endpoints were PFS, OS and safety. All endpoints were evaluated by the local investigator. Results: From May 2012 to May 2018, 173 patients were randomized. Median age was 64 years (25% were at least 70 years), female 34%, PS 0 61%, ESMO group 1/2/3 64%/ 23%/13%. Baseline characteristics were well-balanced between the two groups. Median duration of therapy was 6.2 months in both arms and patients received a median of 11 and 12 cycles, respectively, without any difference in dose-intensity. In arm A and B overall RR was 69% and 78% (p ¼ 0.17), median PFS was 11.9 (arm A) and 11.8 months (arm B) (HR 1.10; p ¼ 0.60), and median OS was 40.7 and 39.2 months (HR 1.05; p ¼ 0.82), respectively. Most important grade 3 adverse events were neutropenia (15% vs 17%), rash (9% vs 15%), diarrhoea (7% vs 11%), fatigue (7% vs 7%), and febrile neutropenia (3% vs 1%); 20% in arm B experienced neuropathy grade 2 (no grade 3). Final and updated PFS and OS with sub-group analysis will be presented. Conclusions: Cet every two weeks in combination with FOLFIRI or alternating FOLFIRI/FOLFOX is well tolerated with high RR and long OS. We recommend FOLFIRI þ cet every 2 weeks in patients with RAS and BRAFwt mCRC. Clinical trial identification: 2011-004188-65. Legal entity responsible for the study: Nordic Biomodulation Group. Funding: Merck. Disclosure: C. Kersten: Research grant / Funding (institution), Licensing / Royalties, Relationship is unrelated to this study: Merck KGaA. All other authors have declared no conflicts of interest.
v208 | Gastrointestinal Tumours, Colorectal
G. Rosati1, F. Galli2, M. Cantore3, S. Lonardi4, M. Banzi5, M.G. Zampino6, R. Mattioli7, N. Pella8, M. Ronzoni9, M. Di Bartolomeo10, S. Tamberi11, P. Marchetti12, S. Bozzarelli13, D.C. Corsi14, A.M. Bochicchio15, F. Artioli16, R. Labianca17, F. Galli18, D. Bilancia19, G. Bregni20 1 Medical Oncology, Azienda Ospedaliera Regionale S. Carlo di Potenza, Potenza, Italy, 2 Statistics Unit, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy, 3 Medical Oncology, Azienda USL 1 di Massa e Carrara, Carrara, Italy, 4Medical Oncology 1 Unit, Istituto Oncologico Veneto IRCCS, Padua, Italy, 5Medical Oncology, Azienda Ospedaliera Arcispedale Santa Maria Nuova - IRCCS, Reggio Emilia, Italy, 6 Medical Oncology, Istituto Europeo di Oncologia, Milan, Italy, 7Oncologia Medica, Azienda Ospedaliera Marche Nord, Fano, Italy, 8Oncologia Medica, Azienda Sanitaria Universitaria Integrata di Udine - Ospedale Santa Maria della Misericordia, Udine, Italy, 9 Oncologia Medica, IRCCS Ospedale San Raffaele, Milan, Italy, 10Oncologia Medica, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, Milan, Italy, 11Oncologia Medica, Ospedale degli Infermi, Faenza, Italy, 12Oncologia Medica, Azienda Ospedaliera St. Andrea, Rome, Italy, 13Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituto Clinico Humanitas, Rozzano, Italy, 14Oncology, Ospedale San Giovanni Calibita - Fatebenefratelli, Rome, Italy, 15Oncologia Medica, Centro di Riferimento Oncologico Basilicata IRCCS, Rionero In Vulture, Italy, 16Ausl Modena, Ospedale Ramazzini, Carpi, Italy, 17Oncologia Medica, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy, 18Statistics Unit, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy, 19Oncologia Medica, Az. Ospedaliera San Carlo, Potenza, Italy, 20 Oncologia Medica 1, IRCCS AOU San Martino - IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy Background: ASCO and ESMO guidelines have identified inadequate sampling of lymph nodes, pT4 primary tumors, obstruction or perforation, lymphovascular and perineural invasion, and poorly differentiated tumors as negative prognostic factors supporting the clinicians in treating their patients with stage II colon cancer (CC). However, the influence of histological subtypes on the risk of death or disease recurrence remains controversial. Methods: The phase III, multicenter, randomized TOSCA trial compared 3 vs. 6 months of fluoropyrimidine-oxaliplatin adjuvant chemotherapy in 3,759 patients with high-risk stage II or stage III CC. Objective of this sub-study was to investigate the role of the histological subtype [(mucinous adenocarcinoma (MUC) or non-mucinous adenocarcinoma (NMUC)] on the impact of the treatment duration in terms of relapse-free survival (RFS) and overall survival (OS) in the subgroup of patients with high-risk stage II, grade 3 CC. Results: Out of 3,614 patients from 130 centres enrolled in the per-protocol population defined in the TOSCA trial, 85 MUC and 389 NMUC patients were included in this analysis. No statistical differences were found between 3 vs. 6 months groups in both histological subgroups in terms of baseline characteristics, except for tumor side. The proportion of patients with right-sided cancer was higher for patients with MUC than NMUC. A significant interaction between treatment duration and histology was observed on both RFS (p ¼ 0.027) and OS (p ¼ 0.017). In the subgroup of patients with MUC, worse RFS (adjusted hazard ratio [HR], 3.95; 95% confidence interval [CI], 1.03–15.17; p ¼ 0.045) and OS (HR, 9.56; 95% CI, 1.14–79.98; p ¼ 0.037) were detected for patients treated in the 3 months arm. No statistically significant differences were detected in the subgroup of patients with NMUC. Conclusions: Both MUC and poorly differentiated subtypes have unfavorable clinical characteristics. Patients with MUC, grade 3, stage II CC require special attention and may need 6 months of oxaliplatin-based chemotherapy. Larger studies are required to clarify the possible negative effect of the histological subtype to improve the prognosis of these patients. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
552P
Exercise improved adjuvant treatment completion rates and treatment-related toxicities in colorectal cancer: A prospective pilot study
H.J. Kim1, Y.J. Shim2, J. Kim1 1 Internal Medicine, Kyung Hee University School of Medicine, Seoul, Republic of Korea, 2 Sports and Leisure, Sungshin Women’s University, Seoul, Republic of Korea Background: The primary aim of this study was to investigate the beneficial effect of exercise on completion rates of adjuvant treatment, which is one of the major prognostic factors among patients with locally advanced colorectal cancer after undergoing curative resection followed by adjuvant treatment. Methods: We assigned patients who were scheduled to undergo adjuvant treatment (N ¼ 39) to the exercise group or the control group in a 2:1 ratio in the order of enrollment. Patients completed questionnaires and underwent assessment of the outcome variables at the start of chemotherapy and upon completion of treatment. Results: A five-fold lower possibility of dose adjustment in the exercise group compared to the control group was demonstrated (odds ratio, 0.188; P ¼ 0.023; 95%
Volume 30 | Supplement 5 | October 2019
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Anticoagulants Intake vs no Antidiarrheals Intake vs no Cardiovascular trts Intake vs no Antidiabetics Intake vs no
DFS
Clinical impact of mucinous and poorly differentiated tumours on the outcome of patients with stage II colon cancer: A TOSCA subgroup analysis
Annals of Oncology Results:
Table: 546P Univariate and multivariate analysis
locally
0.376 0.037 0.075 0.356 0.152 0.102 0.121 0.008
1.409 0.969 0.634 1.179 1.1 1.28 1.42 3.4
0.657 – 3.02 0.940 – 0.998 0.382 – 1.052 0.697 – 2.02 0.646 – 1.92 0.947 – 1.75 0.906 – 2.23 1.26 – 9.6
0.378 0.039 0.078 0.550 0.697 0.106 0.126 0.016
In the Kaplan and meier analysis, recurrence free survival (SLR) was P ¼ 0.03. Independent factors for recurrence were age and ECOG (95% CI 0.940 – 0.998¸ P ¼ 0.037, HR 3.4 95% IC 1.26 – 9.6, P ¼ 0.016). Our findings showed a better SLR in the low dINP subgroup, so we took it as a cutoff 5. Patients who presented a dINP less than 5, have a better SLR in relation to those who have a dINP > 5. P ¼ 0.013. Conclusions: The difference less than 5 between the nutritional index before and after neoadjuvant chemoradiotherapy in patients with locally advanced adenocarcinoma of the rectum is associated with an increase in SLR as an independent predictor of recurrence. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
547P
Short-term clinical outcomes of robotic-assisted total mesorectal excision in rectal cancer after concurrent chemoradiotherapy
P. Chen1, J-Y. Wang2 1 General Surgery, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan, 2 Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan Background: To evaluate the short-term oncological outcomes of robotic-assisted total mesorectal excision (TME) in patients with rectal cancer after neoadjuvant CCRT (concurrent chemoradiotherapy). Methods: We enrolled 120 patients with stages I-IV rectal cancer who underwent robotic-assisted total mesorectal excision (TME) after neoadjuvant concurrent chemoradiotherapy at a single institution between July 2013 and November 2017. Results: Of the 120 patients enrolled, all of them underwent preoperative concurrent chemoradiotherapy. Furthermore, among these 120 patients, 34 (28.3%) achieved a pathologic complete response and 19 people had local or distant recurrences. In a median follow up of 24 months, the 2-year disease-free survival(DFS) and overall survival(OS) were and 84% and 86%. Conclusions: The results demonstrate that robotic-assisted TME for patients with rectal cancer after neoadjuvant CCRT (concurrent chemoradiotherapy) is effective and for patient with tumor invaded to bladder, prostate or uterus, neoadjuvant chemotherapy is a safe and effective way for organ-preserving instead of salvage surgery. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
548P
Local immune status in cancer cell nests can be a predictor of survival for rectal cancer with neoadjuvant radiotherapy
549P
Impact of concomitant medications on disease free survival (DFS) and overall survival (OS) in patients from the PETACC8 study
B. Cle´mence1, J. Taieb2, M. Boulin3, K. Le Malicot4, L.M. Dourthe5, B. Avisse6, P. Laplaige7, C. Borel8, D. Arsene9, F. Kikolski10, B. Denis11, P. Geoffroy12, R. Coriat13, G. Piot14, C. Lepage1 1 Hepatogastroenterology Department, CHU Dijon, Dijon, France, 2Department of Gastroenterology and Digestive Oncology, Hopital European George Pompidou, Paris, France, 3Pharmacy Department, CHU Dijon, Dijon, France, 4Biostatistics, FFCD, Dijon, France, 5Oncology Department, Clinique Sainte Anne, Strasbourg, France, 6 Hepatogastroenterology Department, Centre Hospitalier Pierre Oudot, BourgoinJallieu, France, 7Medical Oncology Department, Polyclinique de Blois, La Chaussee St. Victor, France, 8Medical Oncology Department, Centre Paul Strauss Centre de Lutte Contre le Cancer, Strasbourg, France, 9Oncology Department, CHU de Caen, Caen, France, 10Gastroenterology and Hepatology, Hoˆpital Robert Boulin, Libourne, France, 11 Hepatogastroenterology Department, Hoˆpital Louis Pasteur, Colmar, France, 12 Hepatogastroenterology Department, Clinique Saint-Vincent, Epernay, France, 13 Gastroenterology Department and Digestive Oncology, Hoˆpital Cochin, Paris, France, 14 Oncology Department, Clinique des Ormeaux, Le Havre, France Background: Impact of comedications and comorbidities upon OS isn’t well described in cancer patients (pts). We aimed to evaluate their impacts on DFS and OS on pts resected from a stage III colon cancer and treated by adjuvant FOLFOX-4 þ/- cetuximab in the PETACC8 study. Methods: Treatments (trts) categories were defined according to the WHO ATC classification system. We focused on 4 medication classes: anticoagulant, cardiovascular, antidiarrheal and antidiabetic trts. We classified the 2559 pts in each category if they took trt at baseline or during study whatever the duration was. Kaplan-Meier method and Cox model were used to compare survival curves. Multivariate analyses were performed on the overall population and according to trt arm. Results: Only 1% of pts had no comedications. Comedications with anticoagulant, cardiovascular, antidiarrheal and antidiabetic trts were observed respectively in 18%, 40%, 30% and 9% of the cases. Patients with antidiabetic or cardiovascular trts had more comorbidities. For each other comedication categories, baseline characteristics were balanced between pts treated or not. All comedication categories, except antidiarrheals, were associated with a significant decrease of DFS and OS (Table). Dose-intensity was balanced and may not explain survival differences. For pts treated with at least one cardiac, diabetic or anticoagulant trts, severe events were more frequently reported, including 9 early deaths. The use of antidiarrheals is maybe associated to a better exposure to chemotherapy as reflected by a higher rate of grade 3 adverse events but also a potential better efficacy. Table. Comedications impact on DFS and OS.
X. Lin1, F. Lin2, Q. Zhuang2, X. Zhang2, Y. Huang2, L. Tang2, J. Li3, W. Junxin1 1 Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China, 2Radiation Oncology, Fujian Medical University Cancer Hospital, Fuzhou, China, 3Radiation, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China
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Gender Age body mass index Degree Differentiation ypT ypN Diferencial INP ECOG
Background: Although neoadjuvant chemoradiotherapy is the standard treatment for advanced rectal cancer (LARC), it remains difficult to predict the prognosis of LARC patients. We aimed to explore the impacts of local immune status on survival of LARC after noeadjuvant radiotherapy (nRT). Methods: A total of 76 consecutive LARC patients were enrolled in our institute from February 2012 to September 2015. CD3þ T-cell and CD8þ T-cell count were determined from surgical specimens. Factors associated with disease-free survival (DFS) and overall survival (OS) were identified by univariate and multivariate Cox regression. SPSS 22.0 was used for statistical analyse. Results: The median follow-up time was 29.0 months (range 2.0-59). The Cutoff Finder software identified an optimal CD3þ T-cell cutoff value of 12.5% and CD8þ Tcell value of 9% for our patients. According to the Kaplan-Meier analysis, CD3þ T-cell 12.5% was significantly related to favorable DFS (P ¼ 0.020), while there was no significant difference between CD3þ T-cell and OS (P ¼ 0.238). Meanwhile, CD8þ T-cell 9% was found to have a positive effect on DFS and OS (P ¼ 0.012 and P ¼ 0.035, respectively). In the multivariate Cox regression model, CD8þ T-cell <9% was independent risk factors for poor DFS (HR ¼ 0.492, 95%CI¼ 0.252-0.960, P ¼ 0.038). Furthermore, CD8þ T-cell (HR ¼ 0.268, 95%CI¼ 0.076-0.941, P ¼ 0.040) and T stage (HR ¼ 0.151, 95%CI¼ 0.030-0.7530, P ¼ 0.021) were independent predictors of OS. Conclusions: High CD8þ T-cell count were significantly related to good survival in LARC patients with nRT. Local immune status was suggested to be measured in order to predict the prognosis of patients with LACR after nRT. Legal entity responsible for the study: Xijin Lin. Funding: The Fujian Province Natural Science Foundation (2017J01260), Joint Funds for the Innovation of Science and Technology, Fujian province (2017Y9074), and the Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing (2017 Open Project-9). Disclosure: All authors have declared no conflicts of interest.
abstracts
Annals of Oncology 551P
Table: 549P Overall analysis
OS
HR [95%CI]
p
HR [95%CI]
p
1.33 [1.10–1.62]
.003
1.34 [1.07–1.67]
.01
0.87 [0.73–1.04]
.12
0.78 [0.63–0.96]
.02
1.20 [1.03–1.41]
.02
1.28 [1.07–1.54]
.01
1.37 [1.07–1.76]
.01
1.45 [1.09–1.92]
.01
Conclusions: Comorbidities related to analyzed ATC classes negatively impact OS and DFS in PETACC8 pts, except antidiarrheal agents which positively impact OS and DFS. Clinical trial identification: PETACC8; 2005-003463-23. Legal entity responsible for the study: Fe´de´ration Francophone de Cance´rologie Digestive, Dijon. Funding: Merck and Sanofi. Disclosure: J. Taieb: Advisory / Consultancy: Merck; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Roche Genentech; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Amgen. All other authors have declared no conflicts of interest.
550P
Updated results of NORDIC 8, a randomised trial of cetuximab every 2 weeks with FOLFIRI or cetuximab with alternating FOLFIRI/FOLFOX in patients with RAS and BRAF wild type metastatic colorectal cancer
P. Pfeiffer1, J.K. Bjerregaard2, C. Qvortrup3, H. Sorbye4, B. Glimelius5, C. Kersten6 1 Experimental Research in Medical Cancer Therapy, Odense University Hospital, Odense, Denmark, 2Department of Oncology, Odense University Hospital, Odense, Denmark, 3Department of Oncology, Finsen Centre - Rigshospitalet, Copenhagen, Denmark, 4Oncology, Haukeland Universitetssykehus, Bergen, Norway, 5Section of Experimental and Clinical Oncology, Department of Immunology, Genetics and Pathology, Uppsala, Sweden, 6Centre for Cancer Treatment, Sorlandet Hospital, Kristiansand, Norway Background: Cetuximab (cet) improves efficacy of first-line FOLFIRI in pts with RAS/ RAFwt metastatic colorectal cancer (mCRC). Triplet chemotherapy improves efficacy further but with increased toxicity. Alternating FOLFIRI/FOLFOX is a different way to administer all 3 cytotoxic drugs. We report the updated results from Nordic 8, a multicentre, randomised trial comparing cet with FOLFIRI (arm A) or with FOLFIRI alternating with FOLFOX (arm B). Methods: In this investigator initiated randomised trial, 173 chemo-naı¨ve mCRC patients received cet with FOLFIRI or cet with FOLFIRI (2 cycles) alternating with FOLFOX until PD. Main inclusion criteria were PS 0 or 1, RASwt and ESMO group 1-3 (prior to April 2014 only ESMO group 1 when 36 patients had been included)). The primary endpoint was RR (increase from 60% to 75%) and secondary endpoints were PFS, OS and safety. All endpoints were evaluated by the local investigator. Results: From May 2012 to May 2018, 173 patients were randomized. Median age was 64 years (25% were at least 70 years), female 34%, PS 0 61%, ESMO group 1/2/3 64%/ 23%/13%. Baseline characteristics were well-balanced between the two groups. Median duration of therapy was 6.2 months in both arms and patients received a median of 11 and 12 cycles, respectively, without any difference in dose-intensity. In arm A and B overall RR was 69% and 78% (p ¼ 0.17), median PFS was 11.9 (arm A) and 11.8 months (arm B) (HR 1.10; p ¼ 0.60), and median OS was 40.7 and 39.2 months (HR 1.05; p ¼ 0.82), respectively. Most important grade 3 adverse events were neutropenia (15% vs 17%), rash (9% vs 15%), diarrhoea (7% vs 11%), fatigue (7% vs 7%), and febrile neutropenia (3% vs 1%); 20% in arm B experienced neuropathy grade 2 (no grade 3). Final and updated PFS and OS with sub-group analysis will be presented. Conclusions: Cet every two weeks in combination with FOLFIRI or alternating FOLFIRI/FOLFOX is well tolerated with high RR and long OS. We recommend FOLFIRI þ cet every 2 weeks in patients with RAS and BRAFwt mCRC. Clinical trial identification: 2011-004188-65. Legal entity responsible for the study: Nordic Biomodulation Group. Funding: Merck. Disclosure: C. Kersten: Research grant / Funding (institution), Licensing / Royalties, Relationship is unrelated to this study: Merck KGaA. All other authors have declared no conflicts of interest.
v208 | Gastrointestinal Tumours, Colorectal
G. Rosati1, F. Galli2, M. Cantore3, S. Lonardi4, M. Banzi5, M.G. Zampino6, R. Mattioli7, N. Pella8, M. Ronzoni9, M. Di Bartolomeo10, S. Tamberi11, P. Marchetti12, S. Bozzarelli13, D.C. Corsi14, A.M. Bochicchio15, F. Artioli16, R. Labianca17, F. Galli18, D. Bilancia19, G. Bregni20 1 Medical Oncology, Azienda Ospedaliera Regionale S. Carlo di Potenza, Potenza, Italy, 2 Statistics Unit, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy, 3 Medical Oncology, Azienda USL 1 di Massa e Carrara, Carrara, Italy, 4Medical Oncology 1 Unit, Istituto Oncologico Veneto IRCCS, Padua, Italy, 5Medical Oncology, Azienda Ospedaliera Arcispedale Santa Maria Nuova - IRCCS, Reggio Emilia, Italy, 6 Medical Oncology, Istituto Europeo di Oncologia, Milan, Italy, 7Oncologia Medica, Azienda Ospedaliera Marche Nord, Fano, Italy, 8Oncologia Medica, Azienda Sanitaria Universitaria Integrata di Udine - Ospedale Santa Maria della Misericordia, Udine, Italy, 9 Oncologia Medica, IRCCS Ospedale San Raffaele, Milan, Italy, 10Oncologia Medica, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, Milan, Italy, 11Oncologia Medica, Ospedale degli Infermi, Faenza, Italy, 12Oncologia Medica, Azienda Ospedaliera St. Andrea, Rome, Italy, 13Humanitas Cancer Center, Humanitas Clinical and Research Center, Istituto Clinico Humanitas, Rozzano, Italy, 14Oncology, Ospedale San Giovanni Calibita - Fatebenefratelli, Rome, Italy, 15Oncologia Medica, Centro di Riferimento Oncologico Basilicata IRCCS, Rionero In Vulture, Italy, 16Ausl Modena, Ospedale Ramazzini, Carpi, Italy, 17Oncologia Medica, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy, 18Statistics Unit, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy, 19Oncologia Medica, Az. Ospedaliera San Carlo, Potenza, Italy, 20 Oncologia Medica 1, IRCCS AOU San Martino - IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy Background: ASCO and ESMO guidelines have identified inadequate sampling of lymph nodes, pT4 primary tumors, obstruction or perforation, lymphovascular and perineural invasion, and poorly differentiated tumors as negative prognostic factors supporting the clinicians in treating their patients with stage II colon cancer (CC). However, the influence of histological subtypes on the risk of death or disease recurrence remains controversial. Methods: The phase III, multicenter, randomized TOSCA trial compared 3 vs. 6 months of fluoropyrimidine-oxaliplatin adjuvant chemotherapy in 3,759 patients with high-risk stage II or stage III CC. Objective of this sub-study was to investigate the role of the histological subtype [(mucinous adenocarcinoma (MUC) or non-mucinous adenocarcinoma (NMUC)] on the impact of the treatment duration in terms of relapse-free survival (RFS) and overall survival (OS) in the subgroup of patients with high-risk stage II, grade 3 CC. Results: Out of 3,614 patients from 130 centres enrolled in the per-protocol population defined in the TOSCA trial, 85 MUC and 389 NMUC patients were included in this analysis. No statistical differences were found between 3 vs. 6 months groups in both histological subgroups in terms of baseline characteristics, except for tumor side. The proportion of patients with right-sided cancer was higher for patients with MUC than NMUC. A significant interaction between treatment duration and histology was observed on both RFS (p ¼ 0.027) and OS (p ¼ 0.017). In the subgroup of patients with MUC, worse RFS (adjusted hazard ratio [HR], 3.95; 95% confidence interval [CI], 1.03–15.17; p ¼ 0.045) and OS (HR, 9.56; 95% CI, 1.14–79.98; p ¼ 0.037) were detected for patients treated in the 3 months arm. No statistically significant differences were detected in the subgroup of patients with NMUC. Conclusions: Both MUC and poorly differentiated subtypes have unfavorable clinical characteristics. Patients with MUC, grade 3, stage II CC require special attention and may need 6 months of oxaliplatin-based chemotherapy. Larger studies are required to clarify the possible negative effect of the histological subtype to improve the prognosis of these patients. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
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Exercise improved adjuvant treatment completion rates and treatment-related toxicities in colorectal cancer: A prospective pilot study
H.J. Kim1, Y.J. Shim2, J. Kim1 1 Internal Medicine, Kyung Hee University School of Medicine, Seoul, Republic of Korea, 2 Sports and Leisure, Sungshin Women’s University, Seoul, Republic of Korea Background: The primary aim of this study was to investigate the beneficial effect of exercise on completion rates of adjuvant treatment, which is one of the major prognostic factors among patients with locally advanced colorectal cancer after undergoing curative resection followed by adjuvant treatment. Methods: We assigned patients who were scheduled to undergo adjuvant treatment (N ¼ 39) to the exercise group or the control group in a 2:1 ratio in the order of enrollment. Patients completed questionnaires and underwent assessment of the outcome variables at the start of chemotherapy and upon completion of treatment. Results: A five-fold lower possibility of dose adjustment in the exercise group compared to the control group was demonstrated (odds ratio, 0.188; P ¼ 0.023; 95%
Volume 30 | Supplement 5 | October 2019
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Anticoagulants Intake vs no Antidiarrheals Intake vs no Cardiovascular trts Intake vs no Antidiabetics Intake vs no
DFS
Clinical impact of mucinous and poorly differentiated tumours on the outcome of patients with stage II colon cancer: A TOSCA subgroup analysis