Oral maintenance capecitabine versus active monitoring for patients with metastatic colorectal cancer (mCRC) who are stable or responding after 16 weeks of first-line treatment: Results from the randomized FOCUS4-N trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3504-3504
Author(s):  
Richard Adams ◽  
David Fisher ◽  
Janet Graham ◽  
Jenny F. Seligmann ◽  
Matthew Seymour ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Cox Regression ◽  
Final Analysis ◽  
Line Treatment ◽  
First Line ◽  
Active Monitoring ◽  
Intention To Treat ◽  
First Line Therapy ◽  
First Line Treatment

3504 Background: There is extensive randomised evidence supporting the use of treatment breaks in mCRC, but breaks from treatment are not universally offered to patients despite reductions in toxicity, without detriment to OS. Prior trials have shown that the combination of Cp and bevacizumab extend PFS but not OS. FOCUS4-N explores oral maintenance Cp monotherapy in patients with disease control on first line therapy. Methods: FOCUS4 was a molecularly stratified trial programme registering patients with newly diagnosed mCRC from 88 hospitals in the UK. Whilst undergoing 16 wks of first line treatment, a sample of tumour was sent for laboratory testing to stratify their disease into molecular subtypes: MSI, BRAF, PIK3CA, TP53 and RAS mutations. For some molecular groups, a targeted therapy subtrial was available but entry into the FOCUS4-N trial was offered to those in whom a targeted subtrial was unavailable. Patients were randomised 1:1 between maintenance Cp therapy or AM. The primary outcome was PFS assessed using 8-wkly RECIST reported CT scans with quality of life (using EQ5D 8 weekly) and OS as secondary outcomes. Toxicity and tolerability were assessed 4-wkly. On progression, from the nadir, patients recommenced first line treatment. Cox regression was used to assess efficacy by intention-to-treat (ITT) with adjustment for tumour location, WHO status, metastatic burden, first line treatment and biomarker subtype. Results: Between March 2014 and March 2020, 254 patients were randomised (127 to Cp and 127 to AM). Baseline characteristics were balanced between groups but event rates were higher than anticipated in the AM group and the final analysis was triggered early as a result of the COVID-19 pandemic halting recruitment. The table presents results for PFS and OS. Compliance with treatment was good with per-protocol analysis results very similar to ITT (PFS HR=0.38 (95% CI 0.28-0.51)). Toxicity from Cp v AM was as expected with G≥2 fatigue (25% v 12%), diarrhoea (23% v 13%) and hand-foot syndrome (26% v 3%). Quality of life showed no statistically significant differences between the two arms. Conclusions: Despite strong evidence of prolongation of PFS with maintenance therapy, OS remains unaffected and FOCUS4-N provides additional evidence to support the use of treatment breaks as a safe management alternative for patients who are stable or responding well to first line treatment for mCRC. Cp without bevacizumab may be used to extend PFS, in the interval after 16 weeks of combination therapy. Clinical trial information: ISRCTN#90061546. [Table: see text]

Quality of life of acute myeloid leukemia patients in a real-world setting.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18525-e18525
Author(s):  
Bhavik J. Pandya ◽  
Anna Hadfield ◽  
Bruno C. Medeiros ◽  
Samuel Wilson ◽  
Cat N. Bui ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Acute Myeloid Leukemia ◽  
Real World ◽  
Myeloid Leukemia ◽  
Line Treatment ◽  
First Line ◽  
Real World Setting ◽  
First Line Treatment ◽  
Acute Myeloid

e18525 Background: There is currently limited data on the quality-of-life (QoL) of patients with acute myeloid leukemia (AML) in the real-world setting. The objective of this analysis was to understand the impact of AML on patients receiving first-line treatment vs those who were relapsed/refractory to first-line treatment and therefore on later lines of therapy. Methods: The Adelphi AML Disease-Specific Programme, a real-world, cross-sectional survey involving 61 US hematologists/hemato-oncologists and their consulting AML patients, was conducted between February–May 2015. Physicians provided details on patient demographics and clinical information. Each patient was asked to complete both the EQ-5D-3L and Functional Assessment of Cancer Therapy Leukemia (FACT-Leu). Scores range from −1.09–1 (EQ-5D-3L) and 0–176 (FACT-Leu), where a higher score indicates a better QoL. Data from physician-completed record forms and corresponding patient self-completion forms on a matched sample of 75 patients were analyzed. Results: Of the patients who took part in the survey, 75% (n = 56) were receiving first-line treatment for AML and 25% (n = 19) were relapsed/refractory to first-line treatment and had progressed to later lines of therapy. The first-line patients had a mean age of 56.6 years and an average of 2.1 symptoms whereas the relapsed/refractory patients had a mean age of 56.9 years and an average of 2.4 symptoms, according to the physician. First-line patients may have a directionally better QoL scores than those on later lines of therapy, according to both the EQ-5D (0.75 and 0.71 respectively, P= .51) and the FACT-Leu (103.7 and 92.5 respectively, P= .098) measures. Results from the FACT-Leu-Physical Well-Being sub-domain show that relapsed/refractory patients were significantly more likely than first-line patients to be affected physically by their AML condition (13.0 and 17.6 respectively, P= .005). Conclusions: AML patients who have relapsed or become refractory to first-line treatment report worse QoL than those still on first-line treatments. These observational data shows a need for effective and tolerable treatments that can maintain or improve patients’ QoL, especially for patients with relapsed or refractory disease.

Effect of VEGF and VEGFR polymorphisms on clinical outcome and response in patients with advanced renal cell carcinoma receiving first-line treatment.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 388-388
Author(s):  
Maristella Bianconi ◽  
Mario Scartozzi ◽  
Luca Faloppi ◽  
Cristian Loretelli ◽  
Antonio Zizzi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Nucleotide Polymorphisms ◽  
First Line ◽  
First Line Therapy ◽  
First Line Treatment

388 Background: For the last few years, sunitinib has been considered the standard treatment for first-line metastatic renal cell carcinoma, but in 2010 a new drug pazopanib had been approved for treatment in this setting. Recent data from the COMPARZ and PISCES study seem to suggest a non-inferiority of pazopanib confronted with sunitinib in PFS and OS and a patients’ preference for pazopanib if we consider quality of life parameters. The aim of our study is to investigate whether polymorphisms of VEGF and VEGFR can influence PFS and OS when patients are treated either with sunitinib or pazopanib as first-line treatment. Methods: 97 histologic samples of mRCC patients were tested for VEGF-A, VEGF-C, and VEGFR-1, 2, 3 single nucleotide polymorphisms (SNPs). Patients’ progression free survival (PFS) and overall survival (OS) were analyzed for first-line treatment. Results: In patients treated with sunitinib VEGF-A rs833061 resulted significant in PFS (CC+CT vs TT, p < 0.0001) and OS (p < 0.0001). VEGF-A rs699947 was significant for PFS (AA+AC vs. CC) p = 0.0001) and OS (p < 0.0001). VEGF-A rs2010963 was significant in PFS (CC vs. CG vs. GG, p = 0.0001) and in OS (p = 0.0045). VEGR3 rs6877011 was significant in PFS (CC vs. CG, p = 0.0075) and OS (p = 0.0001). At multivariate analysis rs833061, rs2010963, and rs68877011 were significant in PFS. rs833061 and rs68877011 were independent factors in OS. In the pazopanib treated groups of patients VEGF-A rs833061 resulted significant in PFS (TT+CT vs. CC p = 0.027) Conclusions: In our analysis patients with CC or CT polymorphism of rc833061 had a favourable PFS and OS if treated with sunitinib instead patients treated with pazopanib seems to have benefit if CT+TT polymorphism, A polymorphism rs699947 and G polymorphism of rs2010963 seem to have a better PFS and OS in first line with sunitinib. Patients with C polymorphism of rs6877011 and G polymorphism of rs307822 seem equally to have a favourable impact in first-line therapy with sunitinib. Our data seem to suggest that biology could have a role in the choice of first-line treatment for mRCC patients. Further data will be presented at the Symposium.

Genetic Aberrations and Response to Fludarabine as First Line Treatment in a Serie of B-CLL Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2131-2131
Author(s):  
Pilar Giraldo ◽  
Araceli Rubio-Martinez ◽  
Valle Recasens ◽  
Mikel Valganon ◽  
Paz Latre ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Genetic Alterations ◽  
Fisher Exact Test ◽  
Line Treatment ◽  
First Line ◽  
Genetic Aberrations ◽  
First Line Therapy ◽  
Line Therapy ◽  
First Line Treatment

Abstract Background: Genetic factors have been established in the recent years as the most important independent predictors of disease progression and survival in patients with B-chronic lymphocytic leukaemia (B-CLL). Fludarabine is an approved first-line treatment for B-CLL, which achieves superior remission rates than traditional therapies. The drug is equally effective in early and advanced disease and in younger and elderly patients with B-CLL but different results have been found in patients with cytogenetic aberrations as methylation in the TP53 promoter Aims: To evaluate the response to Fludarabine as first-line therapy in B-CLL patients with advanced stages. Patients and methods: In the study 55 B-CLL patients were enrolled. The diagnosis was established based on standard morphologic and immunophenotypic criteria, and classified on high clinical risk category Rai stage III/IV treated with Fludarabine (25 mg/m2 daily for 5 days IV in a 28-day cycle) as first-line therapy from January 00 to December 03. Response was evaluated after 4 cycles of therapy and in those patients which had not achieved complete remission (CR) two additional cycles were administrated. Criteria for response were established using the revised 1996 NCIWG. FISH studies were performed using the probes LSI p53 (17p13), LSI D13S25 (13q14), CEP 12 and ATM gene (11q22). The sequences of the IGVH genes were determined in cDNA of the patients. Responses to therapy, time to progression disease and overall survival were available to analyse in 41 patients. Association was studied using contingence tables followed by Fisher exact test and to evaluate survival by acturial method of Kaplan Meier and Cox regression. Results: Mean age 64 (36.9–83.9), female 53.7%. 75% of patients presented genetic aberrations associated with worse prognosis: del (17p) and/or del (11q) (45%). No-mutated IGVH genes (57%). Response: 83.5% of patients achieved response (CR 47.8%). Related to genetic aberrations the responses were: 55.5% in patients with del(17p), 75.0% del(11q), 100% +12, 88.8% del(13q) and 100% of patients without genetic alterations showed response to Fludarabine. The 48.8 % of patients developed progression of disease with mean duration of the response of 15.1 months. Related to genetic aberrations the progression was over 81% of patients with genetic aberrations versus 55.5% without genetic alterations (p=0.044). The overall survival was 68.0 months. 34.1% of patients are alive in CR, 36.6% are alive with stable disease 7.3 % are alive with disease in progression and 22.0 % have died. Conclusions: A high response to Fludarabine in first line therapy was observed, however only 55.5% of patients with del(17p) showed response. Patients with genetic aberrations had higher significant rate of progression in comparison with those containing normal genotypes.

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