Survival of Patients With Advanced Colorectal Cancer Improves With the Availability of Fluorouracil-Leucovorin, Irinotecan, and Oxaliplatin in the Course of Treatment

2004 ◽  
Vol 22 (7) ◽  
pp. 1209-1214 ◽  
Author(s):  
Axel Grothey ◽  
Daniel Sargent ◽  
Richard M. Goldberg ◽  
Hans-Joachim Schmoll
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Cytotoxic Agents ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase Iii Trials

Purpose Fluorouracil (FU)-leucovorin (LV), irinotecan, and oxaliplatin administered alone or in combination have proven effective in the treatment of advanced colorectal cancer (CRC). Combination protocols using FU-LV with either irinotecan or oxaliplatin are currently regarded as standard first-line therapies in this disease. However, the importance of the availability of all three active cytotoxic agents, FU-LV, irinotecan, and oxaliplatin, on overall survival (OS) has not yet been evaluated. Materials and Methods We analyzed data from seven recently published phase III trials in advanced CRC to correlate the percentage of patients receiving second-line therapy and the percentage of patients receiving all three agents with the reported median OS, using a weighted analysis. Results The reported median OS is significantly correlated with the percentage of patients who received all three drugs in the course of their disease (P = .0008) but not with the percentage of patients who received any second-line therapy (P = .19). In addition, the use of combination protocols as first-line therapy was associated with a significant improvement in median survival of 3.5 months (95% CI, 1.27 to 5.73 months; P = .0083). Conclusion Our results support the strategy of making these three active drugs available to all patients with advanced CRC who are candidates for such therapy to maximize OS. In addition, our findings suggest that, with the availability of effective salvage options, OS should no longer be regarded as the most appropriate end point by which to assess the efficacy of a palliative first-line treatment in CRC.

K-RAS codon 13 mutation in advanced colorectal cancer: A single-center retrospective study investigating prognostic outcomes and treatment strategies.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 633-633
Author(s):  
Vincenzo Dadduzio ◽  
Michele Basso ◽  
Maria Bensi ◽  
Silvia Cona ◽  
Eleonora Cerchiaro ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Response To Therapy ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line

633 Background: Ras genes are markers of resistance to anti-EGFR therapies. Emerging evidences suggest that each mutation, independently from its predictive role of response/resistance to specific treatments, may be expression of different diseases with different biologic behaviours. We collected data of mCRC patients harbouring K-Ras codon 13 mutation to evaluate response to therapy, PFS and OS. Methods: We retrospectively collected data of advanced colorectal cancer patients harbouring K-Ras codon 13 mutation treated at our Institution between 2004 and 2014. Results: A total of n.33 K-Ras codon 13 mutated patients were analysed. N.24 patients (72,7%) had synchronous metastatic disease. None of the patients received anti-EGFR treatment, while n.25 patients received anti-VEGF agent bevacizumab in association to chemotherapy with fluoropirimidines plus oxaliplatin and/or irinotecan (n.21 as frontline therapy, n.4 in second line). ORR was 51,5% (17/33) on first-line therapy, 22,2% (6/27) on second-line therapy and 16,6% (2/12) on third-line therapy. Median PFS was 14,1 months after first-line therapy, 9,3 months after second-line therapy, 6,4 months after third-line therapy. Median OS was 35,5 months (events: 19/33). N.14 patients received metastases surgery with radical intent. OS in this population has not been reached yet at a median follow-up of 38 months, even though all patients had a relapse. OS among patients undergone to systemic only strategy was 31 months. Conclusions: At our knowledge, this is the first report suggesting a favourable prognosis for K-ras codon 13 mutated patients, with a median overall survival even superior to pan-RAS wild-type patients. Indeed, the high percentage of advanced patients at diagnosis (72.7%), the high responsiveness to chemotherapy even in third line, the high percentage of patients converted to surgery (42.4%) in an unselected population, together with the high risk or relapse after surgery, suggest K-ras codon 13 mutated disease is probably a biologically aggressive disease. Nevertheless our data prompt that these patients may benefit aggressive strategies of treatment and multidisciplinary evaluation.

scholarly journals 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 ◽  
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.

Modified FOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab beyond first progression in advanced colorectal cancer: CCOG-0801 study.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 641-641
Author(s):  
Kiyoshi Ishigure ◽  
Goro Nakayama ◽  
Keisuke Uehara ◽  
Hiroyuki Yokoyama ◽  
Akiharu Ishiyama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Bleeding Event ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
To Receive

641 Background: Bevacizumab provides survival benefit as the first-line and second-line therapies in metastatic colorectal cancer (mCRC). A large observational study suggested use of bevacizumab beyond first progression (BBP) improved survival. This prompted us to conduct a multicenter phase II study of mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizimab in mCRC to further explore the strategy of BBP in Japanese patients. Methods: Previously untreated patients with assessable disease were treated with mFOLFOX6 plus bevacizumab until tumor progression, followed by FOLFIRI plus bevacizumab. The primary endpoint of the study was the second progression-free survival (2nd PFS), defined as duration from enrollment until progression after the second-line therapy. If the patient failed to receive the second-line treatment due to medical reasons or refusal, the PFS during the first-line therapy was used for analysis. Secondary endpoints were PFS, overall survival (OS), response rate (RR), disease control rate (DCR) and safety. Results: In the first-line therapy, 47 patients treated with mFOLFOX6 plus bevacizumab achieved RR of 61.7%, DCR of 89.4% and median PFS of 11.7 months. Thirty patients went on to receive the second-line therapy with FOLFIRI plus bevacizumab and achieved RR of 27.6%, DCR of 62.1%, and median PFS of 6.0 months. Median 2nd PFS was 16.2 months. Median survival time did not reach the median follow-up time of 27.4 months. Severe adverse events associated with bevacizumab during the first-line therapy were a venous thromboembolic event in one case (2%), a grade 2 bleeding event in one case (2%) and GI perforation in one case (2%). However, no critical events associated with bevacizumab were reported during the second-line therapy. Conclusions: The planned continuation of bevacizumab during the second line treatment is feasible in Japanese mCRC patients. A prospective randomized control study to confirm the efficacy has to be conducted in the future.

Assessment of ramucirumab plus paclitaxel as switch maintenance versus continuation of first-line chemotherapy in patients (pts) with advanced HER2-negative gastric or gastroesophageal junction cancers: The ARMANI phase III trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS4151-TPS4151 ◽  
Author(s):  
Federica Morano ◽  
Monica Niger ◽  
Salvatore Corallo ◽  
Sara Lonardi ◽  
Stefano Tamberi ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Phase Iii Trial ◽  
First Line Therapy ◽  
Line Therapy ◽  
Her 2

TPS4151 Background: Platinum/fluoropyrimidine regimens are the backbone of first-line therapy for advanced gastric cancer (AGC). The optimal duration of first-line therapy is still unknown and its continuation until disease progression represents the standard. However this strategy is often associated with cumulative toxicity and rapid development of drug resistance. Moreover, only 40% of AGC pts are eligible for second-line treatment. This study aims at assessing whether switch maintenance to ramucirumab plus paclitaxel will extend the progression-free survival (PFS) of subjects with HER-2 negative AGC who have not progressed after a first-line with a platinum/fluoropyrimidine regimen. The hypothesis is that the early administration of an active, non-cross resistant regimen may delay disease progression and, consequently, improve pts’ quality of life. This strategy may also rescue all those subjects that become ineligible for a second-line therapy due to the rapid clinical deterioration. Methods: This is a randomized, open-label, multicenter, phase III trial. Eligibility criteria are: unresectable/metastatic HER-2 negative AGC or gastroesophageal junction (GEJ) cancer; ECOG PS 0-1; measurable and/or evaluable disease by RECIST v1.1; no progression after 3 months of therapy with either FOLFOX4, mFOLFOX6 or XELOX . The primary endpoint is to compare PFS of pts in ARM A (continuation of the same first-line therapy with oxaliplatin/fluoropyrimidine) versus ARM B (switch maintenance to ramucirumab and placlitaxel). Secondary endpoints are: overall survival, time-to-treatment failure, overall response rate, duration of response, percentage of pts receiving a second-line therapy per treatment arm, safety and quality of life. Exploratory analyses to identify primary resistance and prognosis biomarkers are planned, including Next-Generation Sequencing (NGS) on archival tumor tissues. The ARMANI study is sponsored by the Fondazione IRCCS Istituto Nazionale dei Tumori and it is ongoing at 29 Italian centers with a planned population of 280 pts. Clinical trial information: NCT02934464.

scholarly journals Optimal Sequence and Second-Line Systemic Treatment of Patients with RAS Wild-Type Metastatic Colorectal Cancer: A Meta-Analysis

2021 ◽  
Vol 10 (21) ◽  
pp. 5166
Author(s):  
Chih-Chien Wu ◽  
Chao-Wen Hsu ◽  
Meng-Che Hsieh ◽  
Jui-Ho Wang ◽  
Min-Chi Chang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Meta Analysis ◽  
Second Line ◽  
Wild Type ◽  
First Line ◽  
Second Line Therapy ◽  
Optimal Sequence ◽  
First Line Therapy ◽  
Line Therapy

Although several sequential therapy options are available for treating patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), the optimal sequence of these therapies is not well established. A systematic review and meta-analysis of 13 randomized controlled trials and 4 observational studies were performed, resulting from a search of the Cochrane Library, PubMed, and Embase databases. Overall survival (OS) did not differ significantly in patients with RAS-WT failure who were administered a second-line regimen of changed chemotherapy (CT) plus anti-epidermal growth factor receptor (EGFR) versus only changed CT, changed CT plus bevacizumab versus changed CT plus anti-EGFR, or changed CT versus maintaining CT plus anti-EGFR after first-line therapy with CT, plus bevacizumab. However, OS was significantly different with a second-line regimen that included changed CT plus bevacizumab, versus only changing CT. Analysis of first-line therapy with CT plus anti-EGFR for treatment of RAS-WT mCRC indicated that second-line therapy of changed CT plus an anti-EGFR agent resulted in better outcomes than changing CT without targeted agents. The pooled data study demonstrated that the optimal choice of second-line treatment for improved OS was an altered CT regimen with retention of bevacizumab after first-line bevacizumab failure. The best sequence for first-to-second-line therapy of patients with RAS-WT mCRC was cetuximab-based therapy, followed by a bevacizumab-based regimen.

Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline

2020 ◽  
Vol 38 (36) ◽  
pp. 4317-4345 ◽  
Author(s):  
John D. Gordan ◽  
Erin B. Kennedy ◽  
Ghassan K. Abou-Alfa ◽  
Muhammad Shaalan Beg ◽  
Steven T. Brower ◽  
...  
Keyword(s):  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Advanced Hcc ◽  
First Line Therapy ◽  
Line Therapy ◽  
First Line Treatment

PURPOSE To develop an evidence-based clinical practice guideline to assist in clinical decision making for patients with advanced hepatocellular carcinoma (HCC). METHODS ASCO convened an Expert Panel to conduct a systematic review of published phase III randomized controlled trials (2007-2020) on systemic therapy for advanced HCC and provide recommended care options for this patient population. RESULTS Nine phase III randomized controlled trials met the inclusion criteria. RECOMMENDATIONS Atezolizumab + bevacizumab (atezo + bev) may be offered as first-line treatment of most patients with advanced HCC, Child-Pugh class A liver disease, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1, and following management of esophageal varices, when present, according to institutional guidelines. Where there are contraindications to atezolizumab and/or bevacizumab, tyrosine kinase inhibitors sorafenib or lenvatinib may be offered as first-line treatment of patients with advanced HCC, Child-Pugh class A liver disease, and ECOG PS 0-1. Following first-line treatment with atezo + bev, and until better data are available, second-line therapy with a tyrosine kinase inhibitor may be recommended for appropriate candidates. Following first-line therapy with sorafenib or lenvatinib, second-line therapy options for appropriate candidates include cabozantinib, regorafenib for patients who previously tolerated sorafenib, or ramucirumab (for patients with α-fetoprotein ≥ 400 ng/mL), or atezo + bev where patients did not have access to this option as first-line therapy. Pembrolizumab or nivolumab are also reasonable options for appropriate patients following sorafenib or lenvatinib. Consideration of nivolumab + ipilimumab as an option for second-line therapy and third-line therapy is discussed. Further guidance on choosing between therapy options is included within the guideline. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

Prescribing preferences (PPrefs) of U.S.-based medical oncologists (MOs) for choice of therapy after failure of first-line FOLFOX plus bevacizumab (FFB) in patients with metastatic colorectal cancer (MCC).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 533-533
Author(s):  
Johanna C. Bendell ◽  
Susan L. Britton ◽  
Maria Lankford ◽  
Arden Buettner ◽  
Mark R. Green ◽  
...  
Keyword(s):  
Lung Metastases ◽  
Real Life ◽  
Phase Iii ◽  
Audience Response ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Best Response ◽  
Phase Iii Trials

533 Background: Phase III trials have tested biologic (bio) agents (bevacizumab [bev], anti-EGFR antibodies, ziv aflibercept [ziv]) plus chemotherapy (CT) vs. CT alone after failure of first-line therapy in patients given CT + bev first line. Several have shown improvements in progression-free and overall survival (OS) with the CT + bio approach, but it is not clear how these therapies are being used in the “real life” setting. Methods: Since 3/2013 PPrefs for this setting among 276 MOs were studied using a validated, proprietary, live, case-based market research tool. A core scenario and variations based on KRAS status and first-line therapy outcome were tested (S1, S2, S3, S4). PPref data acquired using blinded audience response technology. All sources of research support were blinded. Core scenario: 49 yr old female with cecal mass, liver/lung metastases, confirmed wt KRAS for S1-3, given FFB first line. S1: FFB x 16 wks → excellent PR → 5FU bev X 16 wks → progressive disease [PD]; S2: FFB x 16 wks → excellent PR → bev alone x 16 wks → PD; S3: FFB → stable disease [SD] x 5 months as best response [BR] → PD; 4) Here changed to mutKRAS; FFB x 8 wks → PD as BR. Results: Findings shown below (Table). Conclusions: In scenarios with wt KRAS, first-line response to FFB, a majority plan bev again second line. If BR to FFB is SD in WT KRAS, anti-EGFR antibody-based therapy is used more often. In S 1-3, ziv is the PPref of 7 - 14% of MOs studied. With mutKRAS and PD as BR to FFB, use of an antiangiogenic + second-line CT is preferred by > 80%, nearly equally split between bev and ziv. Recent phase III trial data showing OS benefits are reflected in current MOs first failure PPrefs. [Table: see text]

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