Quality of life assessment in CLEOPATRA, a phase III study combining pertuzumab with trastuzumab and docetaxel in metastatic breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 598-598 ◽  
Author(s):  
Javier Cortes ◽  
José Baselga ◽  
Young-Hyuck Im ◽  
Graham Ross ◽  
Emma Clark ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Objective Response ◽  
Metastatic Breast ◽  
Exploratory Analysis ◽  
Life Assessment ◽  
Phase Iii ◽  
Her2 Positive ◽  
Cancer Symptoms

598^ Background: CLEOPATRA compared the efficacy and safety of the HER2 dimerization inhibitor pertuzumab (P) plus trastuzumab (T) and docetaxel (D) with placebo (Pla)+T+D in HER2-positive 1st-line MBC. Pts in both arms received a median of 8 cycles of D; Pla/P+T was continued until progressive disease (PD). The safety profile in both arms was similar with a substantial decrease in adverse events (AEs) once chemotherapy finished. The independently assessed progression-free survival was significantly improved with P+T+D compared with Pla+T+D; objective response and duration of response were also improved with P+T+D (Baselga NEJM 2012). Here we report health-related quality of life (HRQoL) data from CLEOPATRA. Methods: Time to deterioration of HRQoL was evaluated using the FACT-B questionnaire and defined as decrease from baseline (BL) of ≥5 points in the TOI-PFB subscale score. Female pts completed questionnaires every 3rd cycle of therapy within 3 days before each tumor assessment until independently determined PD. An exploratory analysis investigated time to deterioration in breast cancer symptoms and functions. Results: 56.7% (Pla+T+D) and 59.5% (P+T+D) of pts experienced deterioration of HRQoL during the study based on TOI-PFB. The median time to deterioration was 18.3 vs 18.4 wks (~6 cycles) (HR 0.97; P = .7161). At Cycle 6, the mean reduction in TOI-PFB score from BL was –3.5 (Pla+T+D) vs –3.0 (P+T+D). At subsequent cycles, when most pts had discontinued D, mean reductions were smaller, suggesting that after an early decline patients’ scores improved slightly. Overall, mean changes were small in both arms. Compliance with completion of the FACT-B questionnaire was ≥75% beyond the 1st year in both arms. An exploratory analysis suggested that time to deterioration in BCS score, which measures symptoms and issues relevant in breast cancer, was delayed with P+T+D (18.3 vs 26.7 wks; HR 0.77; P = .0061). Conclusions: Combining P with T+D appears to have no detrimental effect on HRQoL. Results suggest that P+T+D is associated with a substantial delay in the time to deterioration in BCS score as would be expected given the improved efficacy and the low incidence of AEs once D is discontinued.

Impact of symptoms and toxicity on quality of life: Exploratory analysis of gemcitabine plus docetaxel vs capecitabine plus docetaxel in metastatic breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 682-682 ◽  
Author(s):  
P. Fumoleau ◽  
G. Romieu ◽  
S. Chan ◽  
J. Huober ◽  
M. Tubiana-Hulin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Exploratory Analysis ◽  
Phase Iii ◽  
Serious Adverse Events ◽  
Distress Scale

682 Background: A recent phase III trial comparing gemcitabine-docetaxel (GD) with capecitabine-docetaxel (CD) for metastatic breast cancer (MBC) found comparable progression-free survival but patients (pts) on GD had less toxicity (Chan, ASCO 2005). To better understand how quality of life (QoL) is impacted by toxicity and symptoms, we conducted an exploratory analysis. Methods: The study had 305 pts who relapsed after anthracycline-based treatment either in (neo)adjuvant or first-line MBC. Pts were randomized to GD or CD for 21-day cycles until PD or unacceptable toxicity. QoL was assessed every cycle with Rotterdam Symptom Checklist (RSCL). Only pts with RSCL data were included in the QoL analysis. Comparison between arms of changes from baseline in RSCL dimensions at each cycle were analyzed using analysis of co-variance (ANCOVA). Because the physical symptom distress scale (PSDS) includes symptom- and toxicity-related items, distributions of responses to each item were explored. Results: 302 pts received treatment (GD 152; CD 150); median number of cycles was 6 for both arms. 267 pts (88%) had baseline RSCL data; compliance ranged from 79%-88% for the first 6 cycles. Baseline RSCL scores were comparable between arms. No statistical differences between arms were seen for any of the RSCL dimensions (p>.05 at all cycles). Both arms had worsening in the PSDS (median increases of 3–6.8 on 69-point scale). Numerical differences were seen in some PSDS items rated as “quite a bit” or “very much.” By cycle 3, more GD pts reported tiredness (58% v 47%), lack of energy (45% v 38%), back pain (19% v 9%), and by cycle 2, alopecia (76% v 66%). By cycle 1, more CD pts reported tingling hands/feet (15% v 7%) and burning/sore eyes (14% v 3%). Conclusions: Preliminary analysis indicated no QoL differences between GD and CD; however, further exploration shows that physical distress is explained by different symptoms and toxicities in each arm. Results, particularly at later cycles, should be cautiously interpreted because of pt attrition and different reasons for discontinuation (eg, more CD than GD pts discontinued due to serious adverse events [28% v 13%]). Further analysis incorporating clinical outcomes may better explain QoL outcomes [Table: see text]

scholarly journals Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial

2020 ◽  
Vol 38 (27) ◽  
pp. 3138-3149 ◽  
Author(s):  
Cristina Saura ◽  
Mafalda Oliveira ◽  
Yin-Hsun Feng ◽  
Ming-Shen Dai ◽  
Shang-Wen Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Her2 Positive ◽  
End Points ◽  
Cns Disease

PURPOSE NALA (ClinicalTrials.gov identifier: NCT01808573 ) is a randomized, active-controlled, phase III trial comparing neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), plus capecitabine (N+C) against lapatinib, a reversible dual TKI, plus capecitabine (L+C) in patients with centrally confirmed HER2-positive, metastatic breast cancer (MBC) with ≥ 2 previous HER2-directed MBC regimens. METHODS Patients, including those with stable, asymptomatic CNS disease, were randomly assigned 1:1 to neratinib (240 mg once every day) plus capecitabine (750 mg/m2 twice a day 14 d/21 d) with loperamide prophylaxis, or to lapatinib (1,250 mg once every day) plus capecitabine (1,000 mg/m2 twice a day 14 d/21 d). Coprimary end points were centrally confirmed progression-free survival (PFS) and overall survival (OS). NALA was considered positive if either primary end point was met (α split between end points). Secondary end points were time to CNS disease intervention, investigator-assessed PFS, objective response rate (ORR), duration of response (DoR), clinical benefit rate, safety, and health-related quality of life (HRQoL). RESULTS A total of 621 patients from 28 countries were randomly assigned (N+C, n = 307; L+C, n = 314). Centrally reviewed PFS was improved with N+C (hazard ratio [HR], 0.76; 95% CI, 0.63 to 0.93; stratified log-rank P = .0059). The OS HR was 0.88 (95% CI, 0.72 to 1.07; P = .2098). Fewer interventions for CNS disease occurred with N+C versus L+C (cumulative incidence, 22.8% v 29.2%; P = .043). ORRs were N+C 32.8% (95% CI, 27.1 to 38.9) and L+C 26.7% (95% CI, 21.5 to 32.4; P = .1201); median DoR was 8.5 versus 5.6 months, respectively (HR, 0.50; 95% CI, 0.33 to 0.74; P = .0004). The most common all-grade adverse events were diarrhea (N+C 83% v L+C 66%) and nausea (53% v 42%). Discontinuation rates and HRQoL were similar between groups. CONCLUSION N+C significantly improved PFS and time to intervention for CNS disease versus L+C. No new N+C safety signals were observed.

Phase III Trial of Doxorubicin, Paclitaxel, and the Combination of Doxorubicin and Paclitaxel as Front-Line Chemotherapy for Metastatic Breast Cancer: An Intergroup Trial (E1193)

2003 ◽  
Vol 21 (4) ◽  
pp. 588-592 ◽  
Author(s):  
George W. Sledge ◽  
Donna Neuberg ◽  
Patricia Bernardo ◽  
James N. Ingle ◽  
Silvana Martino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Metastatic Breast Cancer ◽  
Single Agent ◽  
Metastatic Breast ◽  
Complete Response ◽  
Phase Iii ◽  
Global Quality Of Life ◽  
Intergroup Trial

Purpose: Between February 1993 and September 1995, 739 patients with metastatic breast cancer were entered on an Intergroup trial (E1193) comparing doxorubicin (60 mg/m2), paclitaxel (175 mg/m2/24 h), and the combination of doxorubicin and paclitaxel (AT, 50 mg/m2 and 150 mg/m2/24 h, plus granulocyte colony-stimulating factor 5 mg/kg) as first-line therapy. Patients receiving single-agent doxorubicin or paclitaxel were crossed over to the other agent at time of progression. Patients and Methods: Patients were well balanced for on-study characteristics. Results: Responses (complete response and partial response) were seen in 36% of doxorubicin, 34% of paclitaxel, and 47% of AT patients (P = .84 for doxorubicin v paclitaxel, P = .007 for v AT, P = .004 for paclitaxel v AT). Median time to treatment failure (TTF) is 5.8, 6.0, and 8.0 months for doxorubicin, paclitaxel, and AT, respectively (P = .68 for doxorubicin v paclitaxel, P = .003 for doxorubicin v AT, P = .009 for paclitaxel v AT). Median survivals are 18.9 months for patients taking doxorubicin, 22.2 months for patients taking paclitaxel, and 22.0 months for patients taking AT (P = not significant). Responses were seen in 20% of patients crossing from doxorubicin → paclitaxel and 22% of patients crossing from paclitaxel → doxorubicin (P = not significant). Changes in global quality-of-life measurements from on-study to week 16 were similar in all three groups. Conclusion: (1) doxorubicin and paclitaxel, in the doses used here, have equivalent activity; (2) the combination of AT results in superior overall response rates and time to TTF; and (3) despite these results, combination therapy with AT did not improve either survival or quality of life compared to sequential single-agent therapy.

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