P-177 Overall survival of patients with left-sided metastatic colorectal cancer in real life: Experience from University Hospital for Tumors in Zagreb, Croatia

Background Regorafenib is an orally administered multikinase inhibitor that has been approved for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC). Even though regorafenib significantly improved survival in two international phase 3 trials (CORRECT and CONCUR), a high rate of treatment-related toxic effects and dose modifications were observed with a modest benefit. The aim of this study was to provide information concerning the efficacy, safety, and cost of regorafenib in patients with mCRC in clinical practice. Material and Methods We retrospectively reviewed patients treated with regorafenib monotherapy for unresectable mCRC in five Franche-Comté cancer hospitals (France). The primary end point was overall survival. Secondary end points were safety and descriptive cost analyses of patients treated with regorafenib in clinical practice. Another aim of this study was to assess the impact of regorafenib prescription on the risk of hospitalization in real-life practice. Results From January 2014 to August 2014, 29 consecutive patients were enrolled. Patients were heavily pretreated and were refractory to standard chemotherapies. The primary tumor sites were the colon and the rectum for 55% and 45% of patients, respectively. Fifteen patients (51%) harbored an RAS mutation. Eastern Cooperative Oncology Group - Performance Status (PS) was 0–1 for 86% of patients and 2 for 14% of patients. Nineteen patients (66%) initially received reduced doses of 120 or 80 mg/day. The median duration of treatment was 2.5 months (range, 0.13–11.4 months). Treatment-related adverse events occurred in 86% of patients. The most frequent adverse events of any grade were fatigue (35%), diarrhea (20%), and hand-foot skin reaction (20%). Grade 3 or 4 treatment-related adverse events occurred in 10 patients (35%). Three patients (10%) were admitted to hospital due to drug-related severe adverse events. The mean cost of patient management with regorafenib for the duration of treatment was 9908 ± 8191€, and median cost was 7917€ (Interquartile range (IQR) 4469-13,042). The median overall survival was six months (95% confidence interval, five to eight months). Conclusions The safety and efficacy of regorafenib in heavily pretreated mCRC patients was comparable, in our study, to prospective and retrospective trials. Toxic effects were mostly manageable in an outpatient setting. Regorafenib itself represented the most important (93%) part of supported costs. Even though most side effects were manageable in an outpatient setting, severe adverse events occurred from hospitalization in 10% of patients. These data should be confirmed in a larger real-life-based cohort. Identification of predictive biomarkers is needed for mCRC patient selection for regorafenib treatment.

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Drug Holidays and Overall Survival of Patients with Metastatic Colorectal Cancer

Cancers ◽

10.3390/cancers13143504 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3504

Author(s):

Silvio Ken Garattini ◽

Debora Basile ◽

Marta Bonotto ◽

Elena Ongaro ◽

Luca Porcu ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Metastatic Colorectal Cancer ◽

Cox Regression ◽

University Hospital ◽

Continuous Treatment ◽

First Line ◽

Attrition Rates ◽

Treatment Interruptions ◽

The Impact

Different de-escalation strategies have been proposed to limit the risk of cumulative toxicity and guarantee quality of life during the treatment trajectory of patients with metastatic colorectal cancer (mCRC). Programmed treatment interruptions, defined as drug holidays (DHs), have been implemented in clinical practice. We evaluated the association between DHs and overall survival (OS). This was a retrospective study, conducted at the University Hospital of Udine and the IRCCS CRO of Aviano. We retrieved records of 608 consecutive patients treated for mCRC from 1 January 2005 to 15 March 2017 and evaluated the impact of different de-escalation strategies (maintenance, DHs, or both) on OS through uni- and multivariate Cox regression analyses. We also looked at attrition rates across treatment lines according to the chosen strategy. In our study, 19.24% of patients received maintenance therapy, 16.12% DHs, and 9.87% both, while 32.07% continued full-intensity first-line treatment up to progression or death. In uni- and multivariate analyses first-line continuous treatment and early discontinuation (treatment for less than 3 months) were associated to worse OS compared to non-continuous strategies (HR, 1.68; 95% CI, 1.22–2.32; p = 0.002 and HR,4.89; 95% CI, 3.33–7.19; p < 0.001, respectively). Attrition rates were 22.8%, 20.61%, and 19.64% for maintenance, DHs, or both, respectively. For continuous therapy and for treatment of less than 3 months it was 21.57% and 49%. De-escalation strategies are safe and effective options. DHs after initial induction chemotherapy may be considered in clinically selected patients with metastatic colorectal cancer.

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P-209 Multicenter real life experience of biological agents in patients with metastatic colorectal cancer

Annals of Oncology ◽

10.1016/j.annonc.2020.04.291 ◽

2020 ◽

Vol 31 ◽

pp. S158

Author(s):

U. Demirci ◽

I. Ertürk ◽

Ç. Arslan ◽

A. Bilici ◽

D. Çevik ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Life Experience ◽

Real Life ◽

Biological Agents

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Bevacizumab combined with first-line chemotherapy in elderly patients (≥75 years old) with metastatic colorectal cancer: Final results of the noninterventional CASSIOPEE study.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.3547 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 3547-3547

Author(s):

Eric Francois ◽

Denis Michel Smith ◽

Sophie Gourgou ◽

Sophie Gandon ◽

Florence Rollot ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Metastatic Colorectal Cancer ◽

Real Life ◽

Progression Free Survival ◽

Daily Practice ◽

Similar Treatment ◽

Free Survival ◽

Metastatic Sites ◽

Efficacy Population

3547 Background: Approximately half of the patients (pts) with metastatic colorectal cancer (mCRC) are elderly (≥65 years). Although few elderly pts are included in clinical studies, results in mCRC have shown similar treatment benefits in terms of progression-free survival and overall survival in young and elderly pts. This study was conducted in pts ≥75 years-old with mCRC treated in real life 1st line bevacizumab + chemotherapy in order to improve the knowledge on this population and to contribute in optimizing treatment strategy. Methods: CASSIOPEE is a prospective, multicenter, non-interventional study evaluating 1st line combination of bev + chemotherapy over 24 months in pts aged ≥75 years with mCRC. The primary endpoint was to describe progression-free survival (PFS). Secondary endpoints included the description of pts characteristics, overall survival, bev and chemotherapy regimen, safety and autonomy criteria (Lawton Instrumental Activities of Daily Living Scale; Balducci score). Results: A total of 402 pts were included between March 2012 and July 2016. In the efficacy population (n = 358), 52% were men, mean age 81 (±4); 54% were≥ 80 years old and 19% were ECOG ≥2; 80% had primary tumor located in the colon; main metastatic sites: liver (66%) and lung (30%). Bev was mainly combined with Folfox (36%) and Folfiri (29%). Median PFS was 9.1 months [8.3;10.2] in the efficacy population and 9.3 months for pts aged < 80, 9.5 months for pts aged ≥ 80 or ≤ 85 and 8.3 months for pts aged > 85. The PFS rate at 24 months was 11.8%. Median OS was 19.0 months [16.5;21.5] in the efficacy population and 20.6 months for pts aged < 80, 17.8 months for pts aged ≥ 80 or ≤ 85 and 13.0 months for pts aged > 85. The OS rate at 24 months was 42.0%. Autonomy and ECOG status remained stable from baseline to 24 months. In the safety population (n = 383), grade ≥ 3 adverse events occurred in 40% pts including 10% pts with bev related AEs. Overall, 4% pts died of an AE and 0.5% were bev related. Conclusions: These results suggest that mCRC patients aged ≥75 years-old, can benefit from 1st line bev plus chemotherapy in daily practice in this population. The safety profile is acceptable. Clinical trial information: NCT01555762.

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Both XELIRI And TEGAFIRI Togetherwith Bevacizumab are Effective for Recurrent or Metastatic Colorectal Cancer: A Real-Life Experience

10.47829/coo.2020.3101 ◽

2020 ◽

Vol 03 (01) ◽

Author(s):

Hsu TC ◽

Liao PN

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Life Experience ◽

Real Life

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Different Toxicity Profiles Predict Third Line Treatment Efficacy in Metastatic Colorectal Cancer Patients

Journal of Clinical Medicine ◽

10.3390/jcm9061772 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1772

Author(s):

Matthias Unseld ◽

Sebastian Fischöder ◽

Mathias Jachs ◽

Magdalena Drimmel ◽

Alexander Siebenhüner ◽

...

Keyword(s):

Colorectal Cancer ◽

Adverse Events ◽

Metastatic Colorectal Cancer ◽

Cancer Patients ◽

Real Life ◽

Surrogate Marker ◽

University Hospital ◽

Rank Test ◽

Line Treatment ◽

Colorectal Cancer Patients

The nucleoside trifluridine/tipiracil (TAS-102) and the multikinase inhibitor regorafenib significantly improved survival in metastatic colorectal cancer patients (mCRC). Both treatments are characterized by different treatment-related adverse events but detailed analyses of predictive side effects are rare. In this retrospective, observational, real-life study, clinical data on mCRC patients treated with trifluridine/tipiracil or regorafenib at the Medical University of Vienna, Austria and the University Hospital Zurich, Switzerland were collected. The correlation between adverse events and response or survival rates were calculated performing Fisher’s exact test and log-rank test, respectively. Common adverse events of any grade included fatigue (52%), nausea/vertigo (34%), anemia (26%), and leukopenia (22%) in trifluridine/tipiracil patients and fatigue (42%), hand-foot-skin syndrome (36%) and hoarseness (34%) in patients upon regorafenib treatment. In trifluridine/tipiracil patients the prevalence of leukopenia (p = 0.044) and weight loss (p = 0.044) was prognostic, whereas leukopenia (p = 0.044) and neutropenia (p = 0.043) predicted PFS. The disease control rate was not significantly affected. In regorafenib-treated patients, the prevalence of nausea (p = 0.001) was prognostic, while oral mucositis predicted PFS (p = 0.032) as well as the DCR (p = 0.039). In conclusion, we underline the efficacy of trifluridine/tipiracil and regorafenib in the real-life setting. We describe predictive adverse events like neutropenia/leukopenia, which might be used as surrogate marker in anticancer therapy beyond second line treatment.

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Molecular and clinical prognostic factors in metastatic colorectal cancer (CRC) patients (pts): A retrospective study.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.511 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 511-511

Author(s):

Luisa Foltran ◽

Paola Ermacora ◽

Nicoletta Pella ◽

Giuseppe Aprile ◽

Giovanna De Maglio ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Prognostic Factors ◽

Metastatic Colorectal Cancer ◽

Univariate Analysis ◽

University Hospital ◽

Braf V600e ◽

Molecular Profile ◽

Wild Type ◽

Clinical Variables

511 Background: Strong evidence is emerging about the usefulness of mutational profiling for CRC pts. This study aimed to evaluate the overall survival in three molecular groups, taking as reference the all-wild type category: (1) BRAF mutated; (2) KRAS mutated codons 12-13 only; (3) any of KRAS codons 61-146, PIK3CA exon 9-20 or NRAS cod 12-13-61 mutations. Also clinical variables were investigated as potential prognostic factors. Methods: Data of 194 consecutive pts treated for metastatic colorectal cancer (mCRC) at our University Hospital in Udine, Italy, between Jan 2004 and Jan 2013 were reviewed. Point mutations were detected by pyrosequencing platform PyroMark Q96 ID instrument for KRAS/NRAS codons 12, 13, 61, and 146, BRAF exon 15, and PIK3CA exons 9 and 20. Clinical and molecular prognostic factors were identified using the Cox proportional hazards model. Results: The all wild-type population consisted of 76 pts (39%). 62 cases (32%) harboured mutations in KRAS codons 12-13. BRAF V600E mutation was found in 10 (5.2%) samples. Mutations in KRAS 61-146, PIK3CA and NRAS codons were detected in 9 (4.6%), 32 (16.5%) and 6 (3.1%) pts, respectively. All factors significant in univariate analysis were subjected to multivariate analysis (see Table). The all-wild type category had the longest survival (27.7 months). Patients carrying BRAF mutations reported an overall survival of 7.6 months and those with KRAS 12-13 mutation 16.7 months. Conclusions: This study reinforces the prognostic value of a full mutational molecular profile and points out some prognostic clinical factors in CRC. The influence of clinical variables such as right colon cancer, primary tumour not resected, exposure to bevacizumab and lines of chemotherapy need further investigation. [Table: see text]

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