Comparative analysis of the effectiveness of second-line bevacizumab plus chemotherapy in second-line therapy in metastatic colorectal cancer.

619 Background: Advances in molecular biology and a wide introduction to the practice of targeted therapies have improved outcomes and significantly affect the overall survival of patients. To investigate the efficacy and safety of bevacizumab (BEV) beyond first progression combined with chemotherapy (CT) in patients with metastatic colorectal cancer. Methods: 68 patients with mCRC who received chemotherapy treatment at the Department of the Kazakh Research Institute of Oncology and Radiology. Selecting second-line chemotherapy based on oxaliplatin or irinotecan depended of an earlier first-line therapy (FOLFOX, FOLFIRI). The survival rate was calculated by Kaplan-Meier, comparison of survival curves was performed by log-rank. Results: The study included 68 patients, who were randomized from February 2009 to November 2011(to 33 [48.5%] BEV + CT and 35 [51.5%] to CT alone). Analysis of the immediate results of treatment showed that in neither case was not achieved complete response of the tumor. Partial regression in group 1 – 11 (33.3 ± 8.2)%, and group 2 - in 9 (25.7 ± 7.3)%. Stabilization is achieved in 20 (60.6 ± 8.5)% and 23 (6.7 ± 8.0)% of cases, respectively. The progression of the disease was observed in the group 1 in 2 (6.1 ± 4.1)% and 3 (8.6 ± 4.7)% of cases. Median progression-free survival (PFS) and overall survival (OS) was 11.5 months (7-16) and 12.2 months in group 1, and 9.7 months (6-13.2) (PFS), 9.1 months(OS) in group 2, respectively. The adverse event profile was consistent with previously reported data for BEV + CT. BEV-related significant adverse events included bleeding grade 3-4 (1.5 %) and venous thrombosis (2.3 %). Conclusions: Our findings demonstrate that BEV + CT continued beyond progression significantly prolong OS and PFS in second-line therapy mCRC.

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Protocol of the EFFORT study: a prospective study of FOLFIRI plus aflibercept as second-line treatment after progression on FOLFOXIRI plus bevacizumab or during maintenance treatment in patients with unresectable/metastatic colorectal cancer

BMC Cancer ◽

10.1186/s12885-020-07576-9 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Hironaga Satake ◽

Koji Ando ◽

Eiji Oki ◽

Mototsugu Shimokawa ◽

Akitaka Makiyama ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Phase Ii Study ◽

Progression Free Survival ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Free Survival ◽

First Line Therapy ◽

Line Therapy

Abstract Background FOLFOXIRI plus bevacizumab is used as a first-line therapy for patients with unresectable or metastatic colorectal cancer. However, there are no clear recommendations for second-line therapy after FOLFOXIRI plus bevacizumab combination. Here, we describe our planning for the EFFORT study to investigate whether FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC. Methods EFFORT is an open-label, multicenter, single arm phase II study to evaluate whether a FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC. Patients with unresectable or metastatic colorectal cancer who received FOLFOXIRI plus bevacizumab as a first-line therapy will receive aflibercept and FOLFIRI (aflibercept 4 mg/kg, irinotecan 150 mg/m2 IV over 90 min, with levofolinate 200 mg/m2 IV over 2 h, followed by fluorouracil 400 mg/m2 bolus and fluorouracil 2400 mg/m2 continuous infusion over 46 h) every 2 weeks on day 1 of each cycle. The primary endpoint is progression-free survival (PFS). To achieve 80% power to show a significant response benefit with a one-sided alpha level of 0.10, assuming a threshold progression-free survival of 3 months and an expected value of at least 5.4 months, we estimated that 32 patients are necessary. Secondary endpoints include overall survival, overall response rate, safety, and exploratory biomarker analysis for differentiating anti-VEGF drug in 2nd-line chemotherapy for unresectable or metastatic colorectal cancer. Discussion This is the first study to investigate whether FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for unresectable or metastatic colorectal cancer. Switching to a different type of anti-VEGF drug in second-line therapy after FOLFOXIRI plus bevacizumab appears to be an attractive treatment strategy when considering survival benefit. It is expected that this phase II study will prove the efficacy of this strategy and that a biomarker for drug selection will be discovered. Trial registration Japan Registry of Clinical Trials jRCTs071190003. Registered April 18, 2019.

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HGCSG 1301: A multicenter, double-blind, randomized controlled phase II trial comparing Hange-shashin-to versus placebo to prevent diarrhea in patients with metastatic colorectal cancer treated with IRIS/Bev as second-line therapy—Updated analysis of antitumor efficacy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.108 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 108-108

Author(s):

Atsushi Ishiguro ◽

Hiroshi Nakatsumi ◽

Tetsuhito Muranaka ◽

Yasuyuki Kawamoto ◽

Satoshi Yuki ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Progression Free Survival ◽

Controlled Study ◽

Second Line ◽

Second Line Therapy ◽

Double Blind ◽

Line Therapy ◽

Significant Difference ◽

Grade 3

108 Background: IRIS (irinotecan plus S-1) plus bevacizumab (IRIS/Bev) is one of the standard chemotherapies in Japan for metastatic colorectal cancer (mCRC) as the first-line or second-line therapy. The most frequent non-hematological adverse event of IRIS was diarrhea. Hange-shashin-to (HST) is a Kampo medicine which is used in Japan for the treatment of gastritis, stomatitis, and diarrhea. We conducted this study to evaluate the usefulness of HST to prevent diarrhea in patients with mCRC receiving IRIS/Bev as the second-line therapy. Methods: This trial was designed as a multicenter, randomized, double-blind, placebo-controlled study. We administrated HST 2.5g or placebo PO t.i.d. x 3 months from the first treatment course of IRIS/Bev. The primary endpoint is proportion of ≥grade 3 diarrhea assessed by CTCAE v4.0. This study is registered with UMIN-CTR, number UMIN000012276. Results: Between Jan 1, 2014 and Mar 31, 2017, 59 patients from 11 institutes in Japan were randomly assigned to receive HST (n = 28, Group H) or placebo (n = 29, Group P). The proportions of ≥grade 3 diarrhea was 10.7% in Group H and 13.8% in Group P (p = 1.00). The other major adverse events of ≥grade 3 in Group H vs Group P were fatigue (3.6% vs 10.3%), anorexia (14.3% vs 10.3%), and nausea (0.0% vs 3.4%). The overall response rate was 13.6% in Group H vs 7.7% in Group P (p = 0.65). There were not statistically significant differences in median progression-free survival (mPFS), median time to treatment failure (mTTF), and median overall survival (mOS) between Group H and Group P ( mPFS 7.9 vs 5.9 months; p = 0.35; mTTF 3.8 vs 5.6; p = 0.466; mOS 17.0 vs 15.3 months; p = 0.750). Conclusions: Prophylactic HST could not reduce the severity of diarrhea during IRIS/Bev. The update analysis of anti-tumor efficacy showed that IRIS/Bev had promising survival benefit but there is not statistically significant difference between HST and placebo. Clinical trial information: UMIN000012276.

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Randomized Controlled Trial of Reduced-Dose Bolus Fluorouracil Plus Leucovorin and Irinotecan or Infused Fluorouracil Plus Leucovorin and Oxaliplatin in Patients With Previously Untreated Metastatic Colorectal Cancer: A North American Intergroup Trial

Journal of Clinical Oncology ◽

10.1200/jco.2006.06.1317 ◽

2006 ◽

Vol 24 (21) ◽

pp. 3347-3353 ◽

Cited By ~ 150

Author(s):

Richard M. Goldberg ◽

Daniel J. Sargent ◽

Roscoe F. Morton ◽

Charles S. Fuchs ◽

Ramesh K. Ramanathan ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Metastatic Colorectal Cancer ◽

Controlled Trial ◽

Sensory Neuropathy ◽

Second Line ◽

Time To Progression ◽

Second Line Therapy ◽

The North ◽

Line Therapy

Purpose Previously, we reported results of Intergroup N9741, which compared standard bolus fluorouracil (FU), leucovorin, plus irinotecan (IFL) with infused FU, leucovorin, plus oxaliplatin (FOLFOX4) and irinotecan plus oxaliplatin in patients with untreated metastatic colorectal cancer. High rates of grade ≥ 3 toxicity on IFL (resulting in some deaths) led us to reduce the starting doses of both irinotecan and FU by 20% (rIFL). This article compares rIFL with FOLFOX4. Patients and Methods The primary comparison was time to progression, with secondary end points of response rate (RR), overall survival, and toxicity. Results Three hundred five patients were randomly assigned. The North Central Cancer Treatment Group Data Safety Monitoring Committee interrupted enrollment at a planned interim analysis when outcomes crossed predetermined stopping boundaries. The results were significantly superior for FOLFOX4 compared with rIFL for time to progression (9.7 v 5.5 months, respectively; P < .0001), RR (48% v 32%, respectively; P = .006), and overall survival (19.0 v 16.3 months, respectively; P = .026). Toxicity profiles were not significantly different between regimens for nausea, vomiting, diarrhea, febrile neutropenia, dehydration, or 60-day all-cause mortality. Sensory neuropathy and neutropenia were significantly more common with FOLFOX4. Approximately 75% of patients in both arms received second-line therapy; 58% of rIFL patients received oxaliplatin-based second-line therapy, and 55% of FOLFOX4 patients received irinotecan-based regimens as second-line therapy. Conclusion FOLFOX4 led to superior RR, time to progression, and overall survival compared with rIFL. The survival benefit for FOLFOX4 observed in the earlier stage of the study was preserved with equal use of either irinotecan or oxaliplatin as second-line therapy.

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Efficacy and Toxicity of Addition of Bevacizumab to Chemotherapy in Patients with Metastatic Colorectal Cancer

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207322666190119162352 ◽

2019 ◽

Vol 21 (10) ◽

pp. 718-724 ◽

Cited By ~ 2

Author(s):

Wen-Cong Ruan ◽

Yue-Ping Che ◽

Li Ding ◽

Hai-Feng Li

Keyword(s):

Colorectal Cancer ◽

Adverse Event ◽

Metastatic Colorectal Cancer ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Clinical Prognosis ◽

Line Therapy ◽

Significant Difference

Background: Pre-treated patients with first-line treatment can be offered a second treatment with the aim of improving their poor clinical prognosis. The therapy of metastatic colorectal cancer (CRC) patients who did not respond to first-line therapy has limited treatment options. Recently, many studies have paid much attention to the efficacy of bevacizumab as an adjuvant treatment for metastatic colorectal cancer. Objectives: We aimed to evaluate the efficacy and toxicity of bevacizumab plus chemotherapy compared with bevacizumab-naive based chemotherapy as second-line treatment in people with metastatic CRC. Methods: Electronic databases were searched for eligible studies updated to March 2018. Randomized-controlled trials comparing addition of bevacizumab to chemotherapy without bevacizumab in MCRC patients were included, of which, the main interesting results were the efficacy and safety profiles of the addition of bevacizumab in patients with MCRC as second-line therapy. Result: Five trials were eligible in the meta-analysis. Patients who received the combined bevacizumab and chemotherapy treatment in MCRC as second-line therapy showed a longer overall survival (OS) (OR=0.80,95%CI=0.72-0.89, P<0.0001) and progression-free survival (PFS) (OR=0.69,95%CI=0.61-0.77, P<0.00001). In addition, there was no significant difference in objective response rate (ORR) (RR=1.36,95%CI=0.82-2.24, P=0.23) or severe adverse event (SAE) (RR=1.02,95%CI=0.88-1.19, P=0.78) between bevacizumab-based chemotherapy and bevacizumabnaive based chemotherapy. Conclusion: Our results suggest that the addition of bevacizumab to the chemotherapy therapy could be an efficient and safe treatment option for patients with metastatic colorectal cancer as second-line therapy and without increasing the risk of an adverse event.

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