Capecitabine (Cap) and oxaliplatin (Ox) in elderly and/or frail patients with metastatic colorectal cancer: The FOCUS2 trial

9030 Background: Elderly/frail patients, though commonly treated, are under-represented in clinical trials. Evidence is needed to guide choices of drugs and doses in this population. Methods: FOCUS2 is a multicenter, 2x2 factorial randomized trial for patients with unpretreated metastatic colorectal cancer judged unfit for full-dose combination chemotherapy. After comprehensive health assessment (CHA), randomization was to: (A) simplified LV5FU2 infusional fluorouracil/leucovorin (FU); (B) OxFU; (C) Cap; or (D) OxCap. In each case, starting doses were 80% standard, with an option to escalate to full-dose at 6 weeks (wk). The factorial questions were: (A+B v C+D) - does replacing FU with Cap improve quality of life (QL)? (primary endpoint: improved global QL at 12 wk [QLQ-C30]); and (A+C v B+D) - how much does Ox improve efficacy in this population? (primary endpoint: progression-free survival (PFS). Results: 460 patients were randomized, 22% < 70 yrs; 35% 70–75 yrs; 43% > 75 yrs. 22% were performance status (PS) 0; 49% PS1; 29% PS2. Primary comparisons: (see table ): global QL did not favor Cap over FU. Comparison of PFS favored the addition of oxaliplatin but did not reach significance (HR 0.87, 95% CI 0.71–1.06, p=0.16). Secondary comparisons: Compared with FU, Cap did not affect RR, PFS or 60-day mortality, but it increased the risk of gr =3 toxicity. Oxaliplatin significantly improved RECIST response (RR) by wk 12, did not increase gr =3 toxicity or 60-day mortality, but reduced the chance of improved QL at 12 wk. Conclusion: In this frail elderly population, substituting Cap for FU did not improve overall QL or efficacy, and significantly increased toxicity. Addition of Ox gave significantly higher anticancer activity without increasing toxicity, but at the cost of some reduction in QL at 12 wk. Planned analyses include correlating baseline CHA with treatment outcome. [Table: see text] [Table: see text]

Download Full-text

Phase II trial of combined chemotherapy with irinotecan, S-1, and bevacizumab (IRIS/Bev) in patients with metastatic colorectal cancer: Update analysis—Hokkaido Gastrointestinal Cancer Study Group (HGCSG) trial.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.3593 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 3593-3593

Author(s):

Satoshi Yuki ◽

Yoshito Komatsu ◽

Takuto Miyagishima ◽

Takashi Kato ◽

Kazuteru Hatanaka ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Primary Endpoint ◽

Performance Status ◽

Progression Free Survival ◽

Line Treatment ◽

First Line ◽

Free Survival ◽

Grade 3 ◽

First Line Treatment

3593 Background: The FIRIS study (Muro K et al. Lancet Oncol 2010;11:853–860) previously demonstrated the non-inferiority of Irinotecan plus S-1(IRIS) to FOLFIRI for metastatic colorectal cancer(mCRC), with progression-free survival (PFS) as the primary endpoint. We previously reported that IRIS plus bevacizumab(IRIS/bev) is very effective as first-line treatment (Komatsu Y et al. ESMO 2010). We now report the updated results of this study. Methods: Eligible patients had to have mCRC with a confirmed diagnosis of adenocarcinoma, an age of >20 years, ECOG performance status (PS) of 0-1, and no history of prior chemotherapy. S-1 40-60 mg twice daily p.o. was given on days 1-14 and irinotecan 100 mg/m2 and bevacizumab 5 mg/kg i.v. were given on days 1 and 15 of a 28-day cycle. The primary endpoint was safety. The secondary endpoints included overall response (OR), progression-free survival (PFS), and overall survival (OS). Results: The target number of 53 patients was enrolled as of March 2009. The results are reported for 52 patients with evaluable lesions. The clinical characteristics of the patients were as follows. The median age was 63.5 years (range, 48 to 82). The male:female ratio was 3:2. The performance status on the Eastern Cooperative Oncology Group scale was 0. In January 2012, on safety analysis, the incidence of grade 3 or 4 neutropenia was 27%. The incidences of other grade 3 or 4 adverse reactions were as follows: diarrhea, 17%; anorexia, 4%; stomatitis, 2%; hypertension, 21%; and gastrointestinal perforation, 0%. The overall response rate was 63.5%. Three patients had complete response. Thirty patients had partial response, 16 had stable disease, none had progressive disease, and 3 were not evaluable. Median progression-free survival was 17.0 months and median survival time was 39.6 months. Conclusions: IRIS/Bev is a remarkably active and generally well-tolerated first-line treatment for patients with mCRC. Randomized control trial comparing this regimen with oxaliplatin containing regimen(XELOX or mFOLFOX6 plus bevacizumab) is being planned.

Download Full-text

Tumor bulk as a prognostic biomarker and predictor of benefit from anti-EGFR therapy in patients with metastatic colorectal cancer: Analysis of 476 patients from the ARCAD Clinical Trials Program.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.108 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 108-108

Author(s):

Benjamin Adam Weinberg ◽

Manel Rakez ◽

Benoist Chibaudel ◽

Tim Maughan ◽

Richard Adams ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Primary Tumor ◽

Lung Metastases ◽

Performance Status ◽

Progression Free Survival ◽

Predictive Biomarker ◽

Wild Type ◽

Cox Models ◽

Study Results

108 Background: Primary tumor sidedness has emerged as a prognostic and predictive biomarker for patients (pts) with metastatic colorectal cancer (mCRC). Tumor bulk has also been postulated to predict response to anti-EGFR therapy. We sought to evaluate the role of tumor bulk as a predictive biomarker to anti-EGFR therapy in pts with left- (LS) and right-sided (RS) mCRC. Methods: Data from 476 pts with mCRC enrolled across 2 first-line trials of anti-EGFR plus chemotherapy versus chemotherapy were pooled. Pts were included if there was available information on tumor sidedness and tumor bulk. All were KRAS wild-type and BRAF wild-type or unknown BRAF status. The right colon was defined as the cecum through the transverse colon, and the left colon as the splenic flexure through the rectum. Tumor bulk was the mean tumor size of target lesions at baseline, bulky defined as > 3.5 cm. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier and Cox models adjusting for performance status (PS), platelet count, primary tumor (PT) resection, number of metastatic sites, and stratified by study. Results: Pts with bulky tumors (211, 44%) had higher PS, white blood cell and platelet counts, higher CEA, fewer sites of metastatic disease, more liver than lung metastases, and fewer had PT resection. OS and PFS medians in months (mos) are presented in the table with 95% confidence intervals (95%CIs). Bulky tumors had inferior median OS compared with non-bulky (mOS, 17.9 vs. 21.3 mos, HRadj 1.33, 95% CI 1.05-1.69, P = 0.016) although median PFS was similar (mPFS, 8.6 vs. 8.7 mos, HRadj 1.15, 95% CI 0.92-1.42, P = 0.21). Conclusions: Tumor bulk is an independent prognostic factor for OS in KRAS wild-type and BRAF wild-type or unknown BRAF status pts. Pts with non-bulky RS tumors have survival outcomes similar to pts with bulky LS tumors. Although the mPFS for pts with RS tumors treated with anti-EGFR therapy was the lowest across subgroups, this finding was not statistically significant. Further research is warranted into whether pts with bulky RS tumors benefit from anti-EGFR therapy. Clinical trial information: NCT00182715, NCT00640081. [Table: see text]

Download Full-text

Initial experience of TAS-102 chemotherapy in Australian patients with chemorefractory metastatic colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.71 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 71-71

Author(s):

Azim Jalali ◽

Hui-Li Wong ◽

Rachel Wong ◽

Margaret Lee ◽

Lucy Gately ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Febrile Neutropenia ◽

Metastatic Colorectal Cancer ◽

Real World ◽

Performance Status ◽

Progression Free Survival ◽

Median Number ◽

Ecog Performance Status ◽

Number Of Patients

71 Background: For patients with refractory metastatic colorectal cancer (mCRC) treatment with Trifluridine/Tipiracil, also known as TAS-102, improves overall survival. In Australia, TAS-102 was initially made available locally through patients self-funding, later via an industry sponsored Medicine Access Program (MAP) and then via the Pharmaceutical Benefits Scheme (PBS). This study aims to investigate the efficacy and safety of TAS-102 in real world Australian population. Methods: A retrospective analysis of prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry was undertaken. The characteristics and outcomes of patients receiving TAS-102 were assessed and compared to all TRACC patients and those enrolled in the registration study (RECOURSE). Results: Across 13 sites, 107 patients were treated with TAS-102 (non-PBS n = 27, PBS n = 80), The median number of patients per site was 7 (range: 1-17). The median age was 60 years (range: 31-83), compared to 67 for all TRACC patients and 63 for RECOURSE. Comparing registry TAS-102 and RECOURSE patients, 75% vs 100% were ECOG performance status 0-1, 74% vs 79% had initiated treatment more than 18 months from diagnosis of metastatic disease and 39% vs 49% were RAS wild type. Median time on treatment was 10.4 weeks (range: 1.7-32). Median clinician assessed progression-free survival was 3.3 compared to RECIST defined PFS of 2 months in RECOURSE study, while median overall survival was the same at 7.1 months. Two patients (2.3%) had febrile neutropenia and there were no treatment-related deaths in the real-world series, where TAS102 dose at treatment initiation was at clinician discretion. In the RECOURSE study there was a 4% febrile neutropenia rate and one treatment-related death. Conclusions: TRACC registry patients treated with TAS102 were younger than both TRACC patients overall and those from the RECOURSE trial. Less strict application of RECIST criteria and less frequent imaging may have contributed to an apparently longer PFS. However overall survival outcomes achieved with TAS102 in real world patients were comparable to findings from this pivotal trial with an acceptable rate of major adverse events.

Download Full-text

Ziv-aflibercept: A novel angiogenesis inhibitor for the treatment of metastatic colorectal cancer

American Journal of Health-System Pharmacy ◽

10.2146/ajhp130143 ◽

2013 ◽

Vol 70 (21) ◽

pp. 1887-1896 ◽

Cited By ~ 21

Author(s):

Clement Chung ◽

Nisha Pherwani

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Performance Status ◽

Angiogenesis Inhibitor ◽

Progression Free Survival ◽

Phase Iii ◽

Second Line ◽

Patient Response ◽

Line Setting

Abstract Purpose The pharmacology, pharmacokinetics, clinical efficacy, safety, and administration of ziv-aflibercept in combination therapy for metastatic colorectal cancer (mCRC) are reviewed. Summary Ziv-aflibercept (Zaltrap, Regeneron Pharmaceuticals and sanofi-aventis) is a novel recombinant fusion protein that targets the angiogenesis signaling pathway of tumor cells by blocking vascular endothelial growth factor (VEGF) receptors that play a key role in tumor growth and metastasis; it is a more potent VEGF blocker than bevacizumab. Ziv-aflibercept is approved by the Food and Drug Administration for use in combination with fluorouracil, irinotecan, and leucovorin (the FOLFIRI regimen) for second-line treatment of patients with mCRC who have disease progression during first-line oxaliplatin-based chemotherapy. A Phase III trial demonstrated that relative to FOLFIRI therapy alone, the use of ziv-aflibercept was associated with significantly improved patient response, overall survival, and progression-free survival in patients with good performance status at baseline, including some who had received prior bevacizumab therapy. The most common grade 3 or 4 adverse effects associated with ziv-aflibercept use in clinical studies were neutropenia, hypertension, and diarrhea; the U.S. product labeling warns of potential hemorrhage and other treatment-related risks. Conclusion Current clinical data are insufficient to directly compare ziv-aflibercept and bevacizumab when used with standard combination chemotherapy as first- or second-line regimens for mCRC. The role of ziv-aflibercept is currently limited to the second-line setting in combination with irinotecan-based regimens in mCRC patients who have not received irinotecan previously. The role of ziv-aflibercept in chemotherapy for other tumor types is yet to be determined.

Download Full-text

Phase Ib/II trial evaluating the safety, tolerability and immunological activity of durvalumab (MEDI4736) (anti-PD-L1) plus tremelimumab (anti-CTLA-4) combined with FOLFOX in patients with metastatic colorectal cancer

ESMO Open ◽

10.1136/esmoopen-2018-000375 ◽

2018 ◽

Vol 3 (4) ◽

pp. e000375 ◽

Cited By ~ 21

Author(s):

Jean-David Fumet ◽

Nicolas Isambert ◽

Alice Hervieu ◽

Sylvie Zanetta ◽

Jean-Florian Guion ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Checkpoint Inhibitors ◽

Target Therapy ◽

Performance Status ◽

Human Monoclonal Antibody ◽

Eastern Cooperative Oncology Group ◽

Predictive Biomarkers ◽

Progression Free Survival ◽

Mutational Status

Background5-Fluorouracil plus irinotecan or oxaliplatin alone or in association with target therapy are standard first-line therapy for metastatic colorectal cancer (mCRC). Checkpoint inhibitors targeting PD-1/PD-L1 demonstrated efficacy on mCRC with microsatellite instability but remain ineffective alone in microsatellite stable tumour. 5-Fluorouracil and oxaliplatin were known to present immunogenic properties. Durvalumab (D) is a human monoclonal antibody (mAb) that inhibits binding of programmed cell death ligand 1 (PD-L1) to its receptor. Tremelimumab (T) is a mAb directed against the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). This study is designed to evaluate whether the addition of PD-L1 and CTLA-4 inhibition to oxaliplatin, fluorouracil and leucovorin (FOLFOX) increases treatment efficacy.MethodsThis phase II study (ClinicalTrials.gov NCT03202758) will assess the efficacy and safety of FOLFOX/D/T association in patients with mCRC (n=48). Good performance status patients (Eastern Cooperative Oncology Group <2) with untreated, RAS mutational status mCRC will be eligible. Prior adjuvant therapy is allowed provided recurrence is >6 months postcompletion. There is a safety lead in nine patients receiving FOLFOX/D/T. Assuming no safety concerns the study will go on to include 39 additional patients. Patients will receive folinic acid (400 mg/m²)/5-fluorouracil (400 mg/m² as bolus followed by 2400 mg/m2 as a 46-hour infusion)/oxaliplatin (85 mg/m2) every 14 days with D (750 mg) D1 every 14 days and T (75 mg) D1 every 28 days. After six cycles of FOLFOX only D/T will continue until disease progression, death, intolerable toxicity, or patient/investigator decision to stop. Primary endpoint is safety and efficacy according to progression-free survival (PFS); secondary endpoints include overall response rate and quality of life. Hypothesis is that a PFS of 50% at 6 months is insufficient and a PFS of 70.7% is expected (with α=10%, β=10%). Blood, plasma and tumour tissue will be collected and assessed for potential prognostic and predictive biomarkers.

Download Full-text

Reintroduction of oxaliplatin for patients with metastatic colorectal cancer refractory to standard chemotherapy regimens.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.630 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 630-630 ◽

Cited By ~ 1

Author(s):

Tohru Sasaki ◽

Mizutomo Azuma ◽

Wasaburo Koizumi ◽

Tomohisa Egawa ◽

Atsushi Nagashima ◽

...

Keyword(s):

Colorectal Cancer ◽

Adverse Events ◽

Metastatic Colorectal Cancer ◽

Initial Treatment ◽

Performance Status ◽

Progression Free Survival ◽

Standard Chemotherapy ◽

Free Survival ◽

Clinical Benefits ◽

Better Than

630 Background: Reintroduction of oxaliplatin seems to have clinical benefits for patients with metastatic colorectal cancer refractory to standard chemotherapy regimens. A interim analysis of RE-OPEN study reported 38.9% of disease control rate (DCR) in ASCO GI 2013, but it is still unknown who will receive benefits from reintroduction of oxaliplatin. Methods: Among patients in whom oxaliplatin was reintroduced in the 7 participating hospitals, we retrospectively studied patients who had previously received oxaliplatin and irinotecan and patients who had a response of stable disease or better during initial treatment with oxaliplatin. Results: From June 2009 through January 2013, oxaliplatin was reintroduced in 53 patients (31 men and 22 women). The median age was 64 years, and the performance status was 0 in 24 patients and 1 in 29. The reasons for discontinuing initial treatment with oxaliplatin were progressive disease in 36 patients, adverse events in 14 and others in 3. The response rate (RR), DCR, the median progression-free survival (PFS), and the median overall survival were 3.8%, 47.2%, 105 days, and 313 days, respectively. As for adverse events, allergic reactions to oxaliplatin (grade 1 or higher) occurred in 26% of the patients. RR, DCR, and PFS in 44 patients with the oxaliplatin-free-interval (OFI) over 6 months were 4.6%, 54.6%, and 119 days, respectively, and were statistically better than those in 9 patients with OFI less than 6 months (0%, 11.1%, and 84 days). Reintroduction of oxaliplatin with bevacizumab showed better PFS than that without bevacizumab (114 days and 78 days, respectively). Conclusions: Reintroduction of oxaliplatin was suggested to be one option for the management of colorectal cancer that is resistant to standard therapy, especially in patients with OFI over 6 months. Bevacizumab may enhance the results of reintroduction treatment.

Download Full-text

Oxaliplatin rechallenge in patients with metastatic colorectal cancer prior treatment with oxaliplatin.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.785 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 785-785

Author(s):

Jeong-Eun Kim ◽

Yong Sang Hong ◽

Kyu-Pyo Kim ◽

Seong Joon Park ◽

Jae-Lyun Lee ◽

...

Keyword(s):

Colorectal Cancer ◽

Hypersensitivity Reaction ◽

Metastatic Colorectal Cancer ◽

Treatment Option ◽

Performance Status ◽

Progression Free Survival ◽

Complete Response ◽

Cytotoxic Agents ◽

Free Survival ◽

Disease Free

785 Background: With limited number of available cytotoxic agents for the treatment of metastatic colorectal cancer (mCRC) patients (pts), rechallenge of chemotherapy can be considered for continuum of treatment. We investigated the efficacy and feasibility of oxaliplatin rechallenge in mCRC pts who have been already exposed to prior oxaliplatin-based chemotherapy. Methods: mCRC pts, who were re-treated with oxaliplatin-based chemotherapy as second or later line treatment in the presence of evaluable disease, were retrospectively accrued. Only those who remained disease-free or progression-free at least 6 months after the last dose of prior oxaliplatin were included. Results: Between January 2009 and May 2014, 110 pts were retreated with oxaliplatin-based regimen; 42 (38.2%) patients received prior oxaliplatin as adjuvant chemotherapy and 68 (61.8%) as palliative chemotherapy. Median disease-free or progression-free duration after prior oxaliplatin was 15.4 months (range, 12.9-17.6 months). All of them received oxaliplatin rechallenge in combination with fluoropyrimidines. The overall response rate to the oxaliplatin rechallenge was 30.9% (34/110), and the disease-control rate was 68.2% (75/110) with 1 complete response, 33 partial responses, and 41 stable diseases. Median progression-free survival and overall survival with rechallenge of oxaliplatin-based therapy were 5.9 months (95% CI, 4.6-7.2 months) and 19.7 months (95% CI, 11.9-27.5 months), respectively. Grade 2 or 3 neuropathy was observed in 16 patients. Any grade hypersensitivity reaction was observed in 10 patients within 4 cycle of treatment. Among them, 6 patients stopped treatment due to grade 3 or 4 hypersensitivity reaction. Conclusions: Rechallenge of oxaliplatin-based therapy could be a treatment option in patients who achieved at least 6 months of disease-free or progression-free survival with prior oxaliplatin-based chemotherapy, especially in those who have lack of further treatment option with good performance status. However, neurotoxicity and hypersensitivity reaction should be cautiously monitored in this setting.

Download Full-text

Regorafenib (REG) versus trifluridine/tipiracil (TAS-102) as salvage-line in patients with metastatic colorectal cancer refractory to standard chemotherapies (REGOTAS): A propensity score analysis from a JSCCR multicenter observational study.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.3540 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 3540-3540 ◽

Cited By ~ 1

Author(s):

Shota Fukuoka ◽

Toshikazu Moriwaki ◽

Hiroya Taniguchi ◽

Atsuo Takashima ◽

Yosuke Kumekawa ◽

...

Keyword(s):

Colorectal Cancer ◽

Propensity Score ◽

Metastatic Colorectal Cancer ◽

Clinical Outcomes ◽

Propensity Score Analysis ◽

Performance Status ◽

Progression Free Survival ◽

Ecog Performance Status ◽

Cox Models ◽

Multicenter Observational Study

3540 Background: It is unclear which drug of REG or TAS-102 should be used earlier for the patients with metastatic colorectal cancer (mCRC) who have access to both drugs. This study investigated the comparison of the efficacy between REG and TAS-102 in patients with refractory to standard chemotherapies. Methods: The clinical data of patients who were treated with REG or TAS-102 among these drugs naive mCRC patients between Jun 2014 and Sep 2015 were retrospectively delivered from 24 institutions of Japanese Society for Cancer of the Colon and Rectum (JSCCR). The primary endpoint was overall survival (OS). Propensity score (PS) was calculated with a logistic regression, in which using baseline parameters were included. Two methods, adjusted and matched analysis, to take propensity score were used. The clinical outcomes were evaluated with Kaplan-Meier method and Cox models based on PS adjustment and matching. Results: Total of 589 patients were enrolled and 550 patients (223 patients in the REG group and 327 patients in the TAS-102 group) met criteria for inclusion in the analysis. The results from PS adjusted analyses showed that OS was similar between the two groups (HR of TAS-102 to REG, 0.96; 95% confidence interval, 0.78–1.18). There were also no statistically significant differences between two groups for progression-free survival (HR 0.94) and time to ECOG Performance status≥2 (HR 1.00), expect for time to treatment failure (HR 0.81; P = 0.025). In the subgroup analysis, REG showed favorable survival compared with TAS-102 in the age of < 65 years patients and unfavorable survival in ≥65 years patients (P for interaction = 0.012). In the PS matched sample (174 patients in each group), the clinical outcomes were similar to the results of the PS adjusted analysis. Conclusions: Although REG and TAS-102 showed a similar efficacy in mCRC patients with refractory to standard chemotherapies, the choice of the drug by age might affect the survival. Supported by JSCCR. Clinical trial information: UMIN000020416

Download Full-text

Safety, efficacy and patient-reported outcomes with trifluridine/tipiracil in pretreated metastatic colorectal cancer: results of the PRECONNECT study

ESMO Open ◽

10.1136/esmoopen-2020-000698 ◽

2020 ◽

Vol 5 (3) ◽

pp. e000698

Author(s):

Jean-Baptiste Bachet ◽

Lucjan Wyrwicz ◽

Timothy Price ◽

Chiara Cremolini ◽

Jean-Marc Phelip ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Group Performance ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Progression Free Survival ◽

Open Label ◽

Patient Reported ◽

Registration Number ◽

Grade 3

BackgroundIn RECOURSE (, trifluridine/tipiracil significantly improved overall survival and progression-free survival (PFS) versus placebo in patients with pretreated metastatic colorectal cancer (mCRC). PRECONNECT was designed to further characterise safety and clinical use of trifluridine/tipiracil.MethodsIn this ongoing, international, multicentre, open-label trial, patients with pretreated mCRC received oral trifluridine/tipiracil 35 mg/m2 twice daily on days 1–5 and 8–12 of each 28-day cycle. The primary endpoint was safety; secondary endpoints included PFS and quality of life (QoL).Results793 patients (median age 62 years) from 13 countries received trifluridine/tipiracil for a median of 2.84 months (IQR 2.64). Adverse events (AEs) were experienced by 96.7%; the most common (≥20% of patients) were neutropaenia, asthenia/fatigue, nausea, anaemia and diarrhoea. Grade ≥3 AEs occurred in 73.9% of patients, with the most common being neutropaenia (39.1% of patients), anaemia (9.8%) and asthenia/fatigue (5.0%). Median PFS was 2.8 months (95% CI 2.7 to 2.9). Median time to Eastern Cooperative Oncology Group performance status deterioration (≥2) was 8.9 months (range 0.03–14.72). There was no clinically relevant change from baseline in QoL.ConclusionsPRECONNECT showed consistent results with the previously demonstrated safety and efficacy profile of trifluridine/tipiracil, with no new safety concerns identified. QoL was maintained during treatment.Trial registration numberNCT03306394.

Download Full-text