- Email: [email protected]
III upper-rectal cancer
S368
Abstracts
Mount Sinai Hospital, NY. We examined IBD and cancer demographics, CTX treatments and tolerance, cancer recurrence, and survival. Results: We identified 109 patients with IBD [n = 46 (42%) CD; n = 63 (58%) UC] who developed a GI malignancy: 69 (63%) colon adenocarcinoma (adenoCa); 18 (17%) rectal adenoCa, 10 (9%) small bowel adenoCa; 9 (8%) anal squamous cell carcinoma (SCC); 2 (2%) appendiceal carcinoid; and 1 (1%) rectal SCC. At cancer diagnosis, median age was 57 years (range 24−92) and median duration of IBD was 25 years (range 1−59). Of patients with known pathology, cancer stage at diagnosis was 1, 2, 3, 4 in 31 (32%), 26 (27%) 26 (27%), 14(14%). Sixty-nine patients (73%) had active IBD on pathology at the time of cancer diagnosis, 52 (75%) of whom had colorectal cancer. Of patients with known cancer treatment plans, 87 (90%) underwent surgery, 62 (71%) received CTX [Table 1], and 24 (38%) received radiotherapy. Among patients who received CTX, 7 (11%) required dose modifications, 8 (12%) experienced treatment delays; 9 (15%) required treatment discontinuation for an overall treatment modification rate of 13%. Eight (13%) were hospitalized for treatmentrelated toxicities. Of patients with treatment modification or hospitalization for treatment-related toxicities, 67% had active IBD. Median follow up after cancer diagnosis was 21 months (range 1–121 months) and 21 (27%) developed cancer recurrence. There was no difference in overall survival between patients with stage 1 (88%) versus stage 2/3 (78%) cancers (p > 0.05). The difference in 5-year recurrence-free survival in patients with stage 1 (89%) compared to stage 2/3 (54%) cancers was borderline significant (p = 0.05). Conclusions: In this series, most IBD patients with GI malignancies received and completed CTX uneventfully. The incidence of cancer treatment discontinuations and complications resulting in hospitalization is comparable to that reported in the literature. Prospective studies are needed to further assess the relationship between IBD, CTX tolerance, and overall survival. Table 1 Chemotherapy
Number exposed
FOLFOX/CAPOX FOLFIRI 5FU/LV Bevacizumab 5FU/MMC Cetuximab Docetaxel/cisplatin/5FU/LV Regorafenib Panitumumab Carboplatin/paclitaxel >1 line of CTX
36 8 7 6 5 3 1 1 1 1 7
No conflict of interest. 2115 POSTER The role of adjuvant chemotherapy in patients with stage II/III upper-rectal cancer P. Barata1 , D.A. Costa2 , F. Filipe1 , J. Barreira1 , S. Oliveira1 , J. Penedo1 , L. Batarda1 , C. Almeida1 . 1 Centro Hospitalar Lisboa Central, Medical ˆ de Oncologia de Lisboa, Oncology, Lisbon, Portugal; 2 Instituto Portugues Medical Oncology, Lisbon, Portugal Background: Despite the advances in the treatment of rectal cancer, about one third of all patients treated with curative intent will recur. No clear benefit was found with the addition of adjuvant chemotherapy (AC) after preoperative chemo-radiation (CR) and surgery. However, in subgroup analysis, AC might benefit patients with a tumor 10−15 cm from anal verge, according to recent prospective studies and meta-analysis. In this study, we explore the effect of adjuvant fluoropyrimidine-based chemotherapy in patients with stage II/III upper-rectal cancer treated with preoperative CR followed by surgery. Material and Methods: We retrospectively analyzed data of 200 consecutive patients admitted at Central Lisbon Hospital Center, with clinical stage II/III rectal cancer at diagnosis, between 01/2008 and 06/2014. We analyzed the cohort of patients with histologically confirmed rectal cancer between 10 and 15 cm from anal verge, treated with preoperative concomitant long-course radiotherapy and fluorouracil-based chemotherapy, and submitted to R0 resection. The cohort was organized in two groups: patients who received AC and patients who did not receive any adjuvant treatment and underwent observation (O). Patient characteristics and outcomes were evaluated with univariate analysis. Kaplan–Meier curves were used to study the effect of selected variables on survival free
from invasive disease and overall survival; curves were compared with logrank test. Results: Forty-four patients, 70% men, median age 69 (range, 43−83), were identified. Median time between end of CR and surgery was 8.1 weeks (4.9−44). Pathologic complete responses were observed in 30% of the cases. The majority (95%) was submitted to anterior resection. Twentynine patients (66%) received fluorouracil-based chemotherapy, median length of 4 months (2−6). Twenty-seven patients completed planned AC, with no major toxicities. Fifteen patients (34%) underwent observation (O) (mainly to physician’s choice. No significant difference was found in relative proportion of clinical stage II-III disease in these 2 groups. The variables gender, age, time between AC and surgery, histologic regression and staging were not associated with different outcomes, in univariate analysis. The median follow-up period was 2.0 years. Among the 6 relapses seen, all of them occurred in patients treated with AC, mainly after 1 year of follow-up. The lung was the most common site of relapse, in 67% of the cases. The 2-year mortality of the cohort was 20%; among the 9 deaths observed, only 3 were cancer-related no toxic deaths were reported. Conclusions: Despite the limitations of this retrospective analysis, our data does not suggest a benefit with the addition of AC in patients with stage II-III upper-rectal cancer treated with CR and surgery. Prospective studies for this subgroup of patients are warranted. No conflict of interest. 2116 POSTER A multicenter phase I/II study of TAS-102 with bevacizumab for metastatic colorectal cancer refractory to standard therapies (C-TASK FORCE) K. Yamazaki1 , Y. Kuboki2 , T. Nishina3 , E. Shinozaki4 , K. Shitara2 , W. Okamoto2 , T. Kajiwara3 , T. Matsumoto3 , T. Tsushima1 , N. Mochizuki5 , M. Fukutani6 , M. Nakamoto6 , Y. Hasegawa6 , A. Sugama6 , S. Nomura6 , A. Sato6 , A. Ohtsu7 , T. Yoshino2 . 1 Shizuoka Cancer Center, Division of Gastrointestinal Oncology, Shizuoka-pref., Japan; 2 National Cancer Center Hospital East, Department of GI oncology, Chiba-pref., Japan; 3 Shikoku Cancer Center, Department of Gastrointestinal Medical Oncology, Ehime-pref., Japan; 4 Cancer Institute Hospital of Japanese Foundation for Cancer Research, Department of Gastroenterology, Tokyo, Japan; 5 National Cancer Center Hospital East, Department of pharmacy, Chiba-pref., Japan; 6 National Cancer Center, Center for Research Administration and Support, Chiba-pref., Japan; 7 National Cancer Center, Exploratory Oncology Research & Clinical Trial Center, Chiba-pref., Japan Background: In global phase III RECOURSE trial, TAS-102 significantly improved overall survival (OS), progression-free survival (PFS) and disease control rate (DCR) over placebo for metastatic colorectal cancer (mCRC) patients (pts) refractory to standard therapies. In preclinical models, TAS102 with bevacizumab (BEV) demonstrated enhanced activity against CRC cells compared with either drug alone. This phase I/II study was conducted to determine the recommended phase II dose (RP2D) and evaluate the efficacy, safety and pharmacokinetics of this combination in pts with mCRC refractory to standard therapies. Methods: Eligibility criteria were: mCRC pts who were refractory or intolerant to fluoropyrimidines, irinotecan, oxaliplatin, anti-angiogenesis therapy and anti-EGFR antibody (if KRAS wild-type) and had no prior regorafenib treatment. Phase I was designed to determine RP2D in the dose de-escalation design of TAS-102 (35 mg/m2 BID on days 1−5 and 8−12 q4w for level 1 and 30 mg/m2 BID for level −1) with a fixed BEV dose (5 mg/kg q2w). Primary endpoint was centrally assessed PFS rate at 16 weeks in pts treated with RP2D. Using a single stage binomial design, this study required 21 pts, with a centrally assessed PFS rate at 16 weeks of 50% deemed promising and 25% unacceptable (alpha=0.1; beta=0.2). Results: From February to July 2014, 25 pts were enrolled. In phase I, dose-limiting toxicity was not observed in 6 pts at level 1, which was determined as the RP2D. Centrally assessed PFS rate at 16 weeks (n = 21) was 42.9% (80% confidence interval: 27.8–59.0%). Median PFS and DCR by central assessment were 3.7 months and 64.0%, and by investigator assessment were 5.4 months and 72.0%, respectively (n = 25). Median OS was not reach. The median number of treatment cycles was 4 (range: 2−8). The median relative dose intensity of TAS-102 and BEV were 100% (range: 83.3–100%) and 100% (range: 75.0%-100%), respectively. In patients with KRAS exon 2 wild-type tumors (n = 10), median PFS and DCR by central assessment were 3.7 months and 70.0%, and by investigator assessment were 5.4 months and 80.0%, respectively. In patients with KRAS exon 2 mutant-type tumors (n = 15), median PFS and DCR by central assessment were 3.8 months and 60.0%, and by investigator assessment were 3.9 months and 66.7%, respectively. There was no significant difference in PFS or DCR between the KRAS exon 2 mutation status. The most common grade 3 or worse adverse events were neutropenia (68%), anemia (12%),
Abstracts
Mount Sinai Hospital, NY. We examined IBD and cancer demographics, CTX treatments and tolerance, cancer recurrence, and survival. Results: We identified 109 patients with IBD [n = 46 (42%) CD; n = 63 (58%) UC] who developed a GI malignancy: 69 (63%) colon adenocarcinoma (adenoCa); 18 (17%) rectal adenoCa, 10 (9%) small bowel adenoCa; 9 (8%) anal squamous cell carcinoma (SCC); 2 (2%) appendiceal carcinoid; and 1 (1%) rectal SCC. At cancer diagnosis, median age was 57 years (range 24−92) and median duration of IBD was 25 years (range 1−59). Of patients with known pathology, cancer stage at diagnosis was 1, 2, 3, 4 in 31 (32%), 26 (27%) 26 (27%), 14(14%). Sixty-nine patients (73%) had active IBD on pathology at the time of cancer diagnosis, 52 (75%) of whom had colorectal cancer. Of patients with known cancer treatment plans, 87 (90%) underwent surgery, 62 (71%) received CTX [Table 1], and 24 (38%) received radiotherapy. Among patients who received CTX, 7 (11%) required dose modifications, 8 (12%) experienced treatment delays; 9 (15%) required treatment discontinuation for an overall treatment modification rate of 13%. Eight (13%) were hospitalized for treatmentrelated toxicities. Of patients with treatment modification or hospitalization for treatment-related toxicities, 67% had active IBD. Median follow up after cancer diagnosis was 21 months (range 1–121 months) and 21 (27%) developed cancer recurrence. There was no difference in overall survival between patients with stage 1 (88%) versus stage 2/3 (78%) cancers (p > 0.05). The difference in 5-year recurrence-free survival in patients with stage 1 (89%) compared to stage 2/3 (54%) cancers was borderline significant (p = 0.05). Conclusions: In this series, most IBD patients with GI malignancies received and completed CTX uneventfully. The incidence of cancer treatment discontinuations and complications resulting in hospitalization is comparable to that reported in the literature. Prospective studies are needed to further assess the relationship between IBD, CTX tolerance, and overall survival. Table 1 Chemotherapy
Number exposed
FOLFOX/CAPOX FOLFIRI 5FU/LV Bevacizumab 5FU/MMC Cetuximab Docetaxel/cisplatin/5FU/LV Regorafenib Panitumumab Carboplatin/paclitaxel >1 line of CTX
36 8 7 6 5 3 1 1 1 1 7
No conflict of interest. 2115 POSTER The role of adjuvant chemotherapy in patients with stage II/III upper-rectal cancer P. Barata1 , D.A. Costa2 , F. Filipe1 , J. Barreira1 , S. Oliveira1 , J. Penedo1 , L. Batarda1 , C. Almeida1 . 1 Centro Hospitalar Lisboa Central, Medical ˆ de Oncologia de Lisboa, Oncology, Lisbon, Portugal; 2 Instituto Portugues Medical Oncology, Lisbon, Portugal Background: Despite the advances in the treatment of rectal cancer, about one third of all patients treated with curative intent will recur. No clear benefit was found with the addition of adjuvant chemotherapy (AC) after preoperative chemo-radiation (CR) and surgery. However, in subgroup analysis, AC might benefit patients with a tumor 10−15 cm from anal verge, according to recent prospective studies and meta-analysis. In this study, we explore the effect of adjuvant fluoropyrimidine-based chemotherapy in patients with stage II/III upper-rectal cancer treated with preoperative CR followed by surgery. Material and Methods: We retrospectively analyzed data of 200 consecutive patients admitted at Central Lisbon Hospital Center, with clinical stage II/III rectal cancer at diagnosis, between 01/2008 and 06/2014. We analyzed the cohort of patients with histologically confirmed rectal cancer between 10 and 15 cm from anal verge, treated with preoperative concomitant long-course radiotherapy and fluorouracil-based chemotherapy, and submitted to R0 resection. The cohort was organized in two groups: patients who received AC and patients who did not receive any adjuvant treatment and underwent observation (O). Patient characteristics and outcomes were evaluated with univariate analysis. Kaplan–Meier curves were used to study the effect of selected variables on survival free
from invasive disease and overall survival; curves were compared with logrank test. Results: Forty-four patients, 70% men, median age 69 (range, 43−83), were identified. Median time between end of CR and surgery was 8.1 weeks (4.9−44). Pathologic complete responses were observed in 30% of the cases. The majority (95%) was submitted to anterior resection. Twentynine patients (66%) received fluorouracil-based chemotherapy, median length of 4 months (2−6). Twenty-seven patients completed planned AC, with no major toxicities. Fifteen patients (34%) underwent observation (O) (mainly to physician’s choice. No significant difference was found in relative proportion of clinical stage II-III disease in these 2 groups. The variables gender, age, time between AC and surgery, histologic regression and staging were not associated with different outcomes, in univariate analysis. The median follow-up period was 2.0 years. Among the 6 relapses seen, all of them occurred in patients treated with AC, mainly after 1 year of follow-up. The lung was the most common site of relapse, in 67% of the cases. The 2-year mortality of the cohort was 20%; among the 9 deaths observed, only 3 were cancer-related no toxic deaths were reported. Conclusions: Despite the limitations of this retrospective analysis, our data does not suggest a benefit with the addition of AC in patients with stage II-III upper-rectal cancer treated with CR and surgery. Prospective studies for this subgroup of patients are warranted. No conflict of interest. 2116 POSTER A multicenter phase I/II study of TAS-102 with bevacizumab for metastatic colorectal cancer refractory to standard therapies (C-TASK FORCE) K. Yamazaki1 , Y. Kuboki2 , T. Nishina3 , E. Shinozaki4 , K. Shitara2 , W. Okamoto2 , T. Kajiwara3 , T. Matsumoto3 , T. Tsushima1 , N. Mochizuki5 , M. Fukutani6 , M. Nakamoto6 , Y. Hasegawa6 , A. Sugama6 , S. Nomura6 , A. Sato6 , A. Ohtsu7 , T. Yoshino2 . 1 Shizuoka Cancer Center, Division of Gastrointestinal Oncology, Shizuoka-pref., Japan; 2 National Cancer Center Hospital East, Department of GI oncology, Chiba-pref., Japan; 3 Shikoku Cancer Center, Department of Gastrointestinal Medical Oncology, Ehime-pref., Japan; 4 Cancer Institute Hospital of Japanese Foundation for Cancer Research, Department of Gastroenterology, Tokyo, Japan; 5 National Cancer Center Hospital East, Department of pharmacy, Chiba-pref., Japan; 6 National Cancer Center, Center for Research Administration and Support, Chiba-pref., Japan; 7 National Cancer Center, Exploratory Oncology Research & Clinical Trial Center, Chiba-pref., Japan Background: In global phase III RECOURSE trial, TAS-102 significantly improved overall survival (OS), progression-free survival (PFS) and disease control rate (DCR) over placebo for metastatic colorectal cancer (mCRC) patients (pts) refractory to standard therapies. In preclinical models, TAS102 with bevacizumab (BEV) demonstrated enhanced activity against CRC cells compared with either drug alone. This phase I/II study was conducted to determine the recommended phase II dose (RP2D) and evaluate the efficacy, safety and pharmacokinetics of this combination in pts with mCRC refractory to standard therapies. Methods: Eligibility criteria were: mCRC pts who were refractory or intolerant to fluoropyrimidines, irinotecan, oxaliplatin, anti-angiogenesis therapy and anti-EGFR antibody (if KRAS wild-type) and had no prior regorafenib treatment. Phase I was designed to determine RP2D in the dose de-escalation design of TAS-102 (35 mg/m2 BID on days 1−5 and 8−12 q4w for level 1 and 30 mg/m2 BID for level −1) with a fixed BEV dose (5 mg/kg q2w). Primary endpoint was centrally assessed PFS rate at 16 weeks in pts treated with RP2D. Using a single stage binomial design, this study required 21 pts, with a centrally assessed PFS rate at 16 weeks of 50% deemed promising and 25% unacceptable (alpha=0.1; beta=0.2). Results: From February to July 2014, 25 pts were enrolled. In phase I, dose-limiting toxicity was not observed in 6 pts at level 1, which was determined as the RP2D. Centrally assessed PFS rate at 16 weeks (n = 21) was 42.9% (80% confidence interval: 27.8–59.0%). Median PFS and DCR by central assessment were 3.7 months and 64.0%, and by investigator assessment were 5.4 months and 72.0%, respectively (n = 25). Median OS was not reach. The median number of treatment cycles was 4 (range: 2−8). The median relative dose intensity of TAS-102 and BEV were 100% (range: 83.3–100%) and 100% (range: 75.0%-100%), respectively. In patients with KRAS exon 2 wild-type tumors (n = 10), median PFS and DCR by central assessment were 3.7 months and 70.0%, and by investigator assessment were 5.4 months and 80.0%, respectively. In patients with KRAS exon 2 mutant-type tumors (n = 15), median PFS and DCR by central assessment were 3.8 months and 60.0%, and by investigator assessment were 3.9 months and 66.7%, respectively. There was no significant difference in PFS or DCR between the KRAS exon 2 mutation status. The most common grade 3 or worse adverse events were neutropenia (68%), anemia (12%),