without lateral lymph node dissection for low rectal cancer: Which patients can benefit?

abstracts

Annals of Oncology 540P

A phase Ib study of E7046 (AN0025) in combination with radiotherapy/ chemoradiotherapy (RT/CRT) in preoperative treatment of rectal cancer

L. Wyrwicz1, M.P. Saunders2, M. Hall3, J. Ng4, V. Bhagawati Prasad5, N. Lautermilch6, M.M. Rashford6, J. Jin6, S. Formenti4, R. Glynne-Jones3 1 Department Oncology and Radiotherapy, M Sklodowska Curie Memorial Cancer Centre, Warsaw, Poland, 2Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK, 3Department of Radiotherapy, Mount Vernon Cancer Centre, Northwood, UK, 4Radiation Oncology, Weill Cornell Medical College, New York, NY, USA, 5Clinical Research, Eisai Inc, Hatfield, UK, 6Adlai Nortye USA, North Brunswick, NJ, USA

Nortye USA. M.P. Saunders: Honoraria (self): Servier, Merck, Amgen, Sanofi. M. Hall: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche, Tesaro, Clovis Oncology; Advisory / Consultancy: AstraZeneca, Amgen. V. Bhagawati Prasad: Full / Part-time employment: Eisai. N. Lautermilch: Full / Part-time employment: Adlai Nortye. M.M. Rashford: Full / Part-time employment: Adlai Nortye. J. Jin: Full / Part-time employment: Adlai Nortye. S. Formenti: Research grant / Funding (self): Bristol-Myers Squibb, Varian, Janssen, Regeneron, Eisai, Merck, Celldex; Honoraria (self): Bristol-Myers Squibb, Varian, Elekta, Janssen, Regeneron, GlaxoSmithKline, Eisai, AstraZeneca, Merck, Viewray, Bayer. R. Glynne-Jones: Advisory / Consultancy: Eisai, Sanofi, Servier, Amgen. All other authors have declared no conflicts of interest.

541P

Upfront radical surgery with total mesorectal excision (TME) versus preoperative chemoradiotherapy followed by TME in clinical stage II/III patients with rectal cancer: A propensity score analysis

A. Ham1, H.S. Kim1, J.S. Chang2, S.J. Shin1, S-H. beom1, W.S. Koom2, T. Kim3, H. Hur4, B.S. Min4, K.Y. Lee4, N.K. Kim4, J.S. Lim5, J-B. Ahn1 1 Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center Yonsei University College of Medicine, Seoul, Republic of Korea, 2Radiation Oncology, Yonsei Cancer Center Yonsei University College of Medicine, Seoul, Republic of Korea, 3 Division of Gastroenterology, Department of Internal Medicine, Yonsei Cancer Center Yonsei University College of Medicine, Seoul, Republic of Korea, 4Surgical Oncology, Yonsei Cancer Center Yonsei University College of Medicine, Seoul, Republic of Korea, 5 Radiology, Yonsei Cancer Center Yonsei University College of Medicine, Seoul, Republic of Korea Background: Although the current standard preoperative chemoradiotherapy (PCRT) for stage II/III rectal cancer decreases the risk of local recurrence, it does not improve overall survival and increase the likelihood of preoperative overtreatment, especially in patients without the circumferential resection margin (CRM) involvement. Methods: Stage II/III rectal cancer without CRM involvement and lateral lymph node metastasis was radiologically defined by preoperative magnetic resonance imaging (MRI). Patients who received either PCRT followed by TME (PCRT group) or upfront surgery with TME (US group) between 2011 and 2016 were analyzed. We derived cohorts of PCRT group versus US group using propensity-score matching using

Volume 30 | Supplement 5 | October 2019

542P

Neoadjuvant chemoradiotherapy with/without lateral lymph node dissection for low rectal cancer: Which patients can benefit?

D. Nishizaki1, K. Hida1, A. Sumii1, Y. Sakai1, T. Konishi2, T. Akagi3, T. Yamaguchi2, T. Akiyoshi2, M. Fukuda4, S. Yamamoto5, S. Maruyama6, M. Okajima7, Y. Miyakura8, R. Okamura1, S. Arizono9, M. Yamamoto10, K. Kawada1, S. Morita11, M. Watanabe12 1 Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan, 2 Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan, 3Department of Surgery, Oita University Faculty of Medicine, Yufu, Japan, 4Department of Surgery, Kitano Hospital, Osaka, Japan, 5Department of Surgery, Hiratsuka Municipal Hospital, Hiratsuka, Japan, 6 Department of Surgery, Niigata Cancer Center Hospital, Niigata, Japan, 7Department of Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan, 8Department of Surgery Saitama Medical Center, Jichi Medical University, Saitama, Japan, 9 Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan, 10Department of Human Ecology, Okayama University Graduate School of Environmental and Life Science, Okayama, Japan, 11 Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan, 12Department of Surgery, Kitasato University Kitasato Institute Hospital, Tokyo, Japan Background: Guidelines for rectal cancer treatment differ in Japan, Europe, and the United States. Neoadjuvant chemoradiotherapy (CRT) has been used to control lateral lymph nodes (LLNs) in the West. The usefulness of LLN dissection (LLND) has been discussed in Japan, and a randomized study stated the possible advantage of local control. However, it is still unclear whether adding LLND to CRT is beneficial. Methods: To investigate the effectiveness of LLND on rectal cancer patients who underwent neoadjuvant CRT, we retrospectively collected magnetic resonance images (MRIs) in a cohort of 1500 patients with cStage II/III lower rectal cancer below the peritoneal reflection and centrally reviewed MRIs. We measured short-axis LLN sizes on pre- and post-CRT images and evaluated patients’ prognosis according to LLN size and whether LLND was performed. Results: MRIs were collected from 752 patients, of whom 189 underwent neoadjuvant CRT. Both pre- and post-CRT MRIs were available in 155 patients, of whom 66 underwent LLND (LLND group) and 89 did not (non-LLND group). The LLND and nonLLND group showed the following differences: positive circumferential resection margin by MRI after CRT: 53.0% vs. 32.6%; positive extramural venous invasion: 36.4% vs. 24.7%; laparoscopic surgery: 39.4% vs. 88.8%; and mean pre-CRT LLN size: 5.2 mm vs. 3.6 mm. Five-year relapse-free survival (5y-RFS) was 73.8% and 66.1% in the LLND and non-LLND groups, respectively (p ¼ 0.38). Two local recurrences occurred in the LLND group. In stratified analysis, 5y-RFS of 40 patients whose LLN size was 5 mm in pre-CRT images was 77.8% in the LLND group and 46.2% in the non-LLND group (p ¼ 0.06). On the other hand, 115 patients whose LLN size was <5 mm in pre-CRT images showed almost no difference between the LLND and non-LLND group (5yRFS: 71.1% vs. 69.5%, p ¼ 0.85). Conclusions: Our data indicated that adding LLND to CRT may have survival benefits on those who had LLN size of  5 mm before CRT. Stratification by short-axis LLN size using pre-CRT MRIs may facilitate optimal multidisciplinary treatment strategies for low rectal cancer. Legal entity responsible for the study: Department of Surgery, Kyoto University Graduate School of Medicine. Funding: The Japanese Foundation for Research and Promotion of Endoscopy, The Japan Society of Clinical Oncology, and Kondou Kinen Medical Foundation. Disclosure: All authors have declared no conflicts of interest.

doi:10.1093/annonc/mdz246 | v205

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Background: AN0025 (previously E7046) is a selective inhibitor of the EP4 receptor and targets macrophages and immunosuppressive cells of myeloid lineage in tumor microenvironment. Preclinical studies have shown potent antitumor activity with AN0025 combining with RT and animal model data suggested antitumor memory Tcell response development by the combination. Neoadjuvant treatment of high-risk rectal cancer provides the platform to test such novel agents to clarify safety and efficacy and provide biopsy and surgical specimens for biomarker analysis. Methods: This is a multicenter, open-label, Phase 1b study in patients (pts) with poor prognosis locally advanced rectal cancer as defined by standard MRI. This ongoing study enrolled pts into two groups, AN0025 in combination with Long Course Radio Chemotherapy (LCRT), or Short Course Radiotherapy (SCRT) followed by chemotherapy. The dose escalation design comprised 2 dose levels, 250mg and 500mg QD for both SCRT and LCRT. Treatment duration was 10 weeks followed by surgery at week 14-16. Pre-surgery MRI was done at week 11-13. Primary objective was safety and tolerability of AN0025 þ CRT. Results: As of 23 Apr 2019, 27 pts were enrolled. 14 pts were treated in 250 mg cohort with 7 pts in LCRT and in SCRT. No DLT was observed among 13 evaluable pts in this dose level. 500mg cohort is ongoing, 13 pts enrolled. Overall, 18 (66.7%) pts had treatment-related AEs (TRAE), most commonly fatigue (25.9%), diarrhea (14.8%), nausea (11.1%), decreased appetite (11.1%), headache (11.1%), and paraesthesia (11.1%). 2 pts experienced grade 3 TRAEs (diarrhea and fatigue) and 1 pt had serious TRAEs (abdominal pain, vomiting, and fatigue). Median age was 59, 74% were male, 41% had ECOG 1, 56% with T stage T3c-T4b, and 63% were EMVIþ. For 250 mg cohort, presurgery MRI showed 6/13 pts had downstaging in T stage (3 each in LCRT and SCRT) and mrTRG 1-2 rate was 46% (43% and 50% in LCRT and SCRT respectively). Clinical responses led to 5/13 pts (38%) managed by a watch-and-wait approach. Conclusions: AN0025 was well tolerated in combination with chemoradiation and preliminary efficacy results are encouraging. Additional safety and efficacy data will be presented. Clinical trial identification: NCT03152370. Legal entity responsible for the study: Adlai Nortye USA. Funding: Adlai Nortye USA. Disclosure: L. Wyrwicz: Honoraria (self), Honoraria (institution): EISAI; Honoraria (self): Adlai

staging, age, and distance from anal verge). Three-year relapse-free survival rate, disease-free survival (DFS), and overall survival (OS) were compared between two groups. Results: A total of 221 patients were analyzed after propensity score matching. There were no differences in baseline characteristics. The median follow-up was 75 months (range, 28-101). No difference in 3-year relapse-free survival rate was noted between PCRT and US groups (89% vs 92% with US; P ¼ 0.657). Likewise, there was no statistically significant difference in DFS (7.7 years vs 8.0 years with US; P ¼ 0.162) and OS (8.1 years vs 8.3 years with US; P ¼ 0.431), respectively. The rates of locoregional recurrence (2.9% vs 0% with US, P ¼ 0.301) and distant metastasis (7.4% vs 7.1%, P ¼ 1.0) at 3-years were not significantly different between two groups. Interestingly, approximately half of patients had pathologic stage I cancer in both groups (56% with PCRT vs 45% with US; P ¼ 0.167) and 69% of patients in US group had not received adjuvant treatment, suggesting that upfront surgery without neoadjuvant therapy can be considered in early stage patients with good prognosis. Conclusions: PCRT may not be required for all stage II/III rectal cancer patients, especially for the MRI-based intermediate-risk group (cT1-2/N1, cT3N0) without CRM involvement and lateral lymph node metastasis. Further prospective studies are warranted. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.