Everolimus plus exemestane for hormone-receptor-positive,human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2

BackgroundThe BOLERO-2 study previously demonstrated that adding everolimus (EVE) to exemestane (EXE) significantly improved progression-free survival (PFS) by more than twofold in patients with hormone-receptor-positive (HR⁺), HER2-negative advanced breast cancer that recurred or progressed during/after treatment with nonsteroidal aromatase inhibitors (NSAIs). The overall survival (OS) analysis is presented here.Patients and methodsBOLERO-2 is a phase III, double-blind, randomized international trial comparing EVE 10 mg/day plus EXE 25 mg/day versus placebo (PBO) + EXE 25 mg/day in postmenopausal women with HR⁺ advanced breast cancer with prior exposure to NSAIs. The primary end point was PFS by local investigator assessment; OS was a key secondary end point.ResultsAt the time of data cutoff (3 October 2013), 410 deaths had occurred and 13 patients remained on treatment. Median OS in patients receiving EVE + EXE was 31.0 months [95% confidence interval (CI) 28.0–34.6 months] compared with 26.6 months (95% CI 22.6–33.1 months) in patients receiving PBO + EXE (hazard ratio = 0.89; 95% CI 0.73–1.10; log-rank P = 0.14). Poststudy treatments were received by 84% of patients in the EVE + EXE arm versus 90% of patients in the PBO + EXE arm. Types of poststudy therapies were balanced across arms, except for chemotherapy (53% EVE + EXE versus 63% PBO + EXE). No new safety concerns were identified.ConclusionsIn BOLERO-2, adding EVE to EXE did not confer a statistically significant improvement in the secondary end point OS despite producing a clinically meaningful and statistically significant improvement in the primary end point, PFS (4.6-months prolongation in median PFS; P < 0.0001). Ongoing translational research should further refine the benefit of mTOR inhibition and related pathways in this treatment setting.Trial registration numberNCT00863655.     

Efficacy of everolimus with exemestane versus exemestane alone in Asian patients with HER2-negative,hormone-receptor-positive breast cancer in BOLERO-2

Background

The addition of mTOR inhibitor everolimus (EVE) to exemestane (EXE) was evaluated in an international, phase 3 study (BOLERO-2) in patients with hormone-receptor-positive (HR⁺) breast cancer refractory to letrozole or anastrozole. The safety and efficacy of anticancer treatments may be influenced by ethnicity (Sekine et al. in Br J Cancer 99:1757–62, 2008). Safety and efficacy results from Asian versus non-Asian patients in BOLERO-2 are reported.

Methods

Patients were randomized (2:1) to 10 mg/day EVE + EXE or placebo (PBO) + EXE. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rate, clinical benefit rate, and safety.

Results

Of 143 Asian patients, 98 received EVE + EXE and 45 received PBO + EXE. Treatment with EVE + EXE significantly improved median PFS versus PBO + EXE among Asian patients by 38 % (HR = 0.62; 95 % CI, 0.41–0.94). Median PFS was also improved among non-Asian patients by 59 % (HR = 0.41; 95 % CI, 0.33–0.50). Median PFS duration among EVE-treated Asian patients was 8.48 versus 4.14 months for PBO + EXE, and 7.33 versus 2.83 months, respectively, in non-Asian patients. The most common grade 3/4 adverse events (stomatitis, anemia, elevated liver enzymes, hyperglycemia, and dyspnea) occurred at similar frequencies in Asian and non-Asian patients. Grade 1/2 interstitial lung disease occurred more frequently in Asian patients. Quality of life was similar between treatment arms in Asian patients.

Conclusion

Adding EVE to EXE provided substantial clinical benefit in both Asian and non-Asian patients with similar safety profiles. This combination represents an improvement in the management of postmenopausal women with HR⁺/HER2^? advanced breast cancer progressing on nonsteroidal aromatase inhibitors, regardless of ethnicity.     

International field testing of the reliability and validity of the EORTC QLQ-BM22 module to assess health-related quality of life in patients with bone metastases

BACKGROUND:

The objective of this international field study was to test the reliability, validity, and responsiveness of the European Organization for Research and Treatment of Cancer (EORTC) QLQ‐BM22 module to assess health‐related quality of life (HRQOL) in patients with bone metastases.

METHODS:

Patients undergoing a variety of bone metastases‐specific treatments were accrued. The QLQ‐BM22 was administered with the QLQ‐C30 at baseline and at 1 follow‐up time point internationally. A debriefing questionnaire was administered to determine patient acceptability and understanding.

RESULTS:

Large‐scale field testing of the QLQ‐BM22 in addition to the QLQ‐C30 took place in 7 countries: Brazil, Canada, Cyprus, Egypt, France, India, and Taiwan. A total of 400 patients participated. Multitrait scaling analyses confirmed 4 scales in the 22‐item module. The scales were able to discriminate between clinically distinct patient groups, such as between those with a poor and those with a better performance status. The QLQ‐BM22 was well received in all 7 countries, and the majority of patients did not recommend any significant changes from the module in its current form.

CONCLUSIONS:

The final QLQ‐BM22 module contains 22 items and 4 scales assessing Painful Sites, Painful Characteristics, Functional Interference, and Psychosocial Aspects. Results confirmed the validity, reliability, cross‐cultural applicability, and sensitivity of the 22‐item EORTC QLQ‐BM22. It is therefore recommended that the QLQ‐BM22 be used in addition to the QLQ‐C30 in clinical trials to assess HRQOL in patients with bone metastases. Cancer 2012;. © 2011 American Cancer Society.     

Incidence and time course of everolimus-related adverse events in postmenopausal women with hormone receptor-positive advanced breast cancer: insights from BOLERO-2

BackgroundIn the BOLERO-2 trial, everolimus (EVE), an inhibitor of mammalian target of rapamycin, demonstrated significant clinical benefit with an acceptable safety profile when administered with exemestane (EXE) in postmenopausal women with hormone receptor-positive (HR⁺) advanced breast cancer. We report on the incidence, time course, severity, and resolution of treatment-emergent adverse events (AEs) as well as incidence of dose modifications during the extended follow-up of this study.Patients and methodsPatients were randomized (2:1) to receive EVE 10 mg/day or placebo (PBO), with open-label EXE 25 mg/day (n = 724). The primary end point was progression-free survival. Secondary end points included overall survival, objective response rate, and safety. Safety evaluations included recording of AEs, laboratory values, dose interruptions/adjustments, and study drug discontinuations.ResultsThe safety population comprised 720 patients (EVE + EXE, 482; PBO + EXE, 238). The median follow-up was 18 months. Class-effect toxicities, including stomatitis, pneumonitis, and hyperglycemia, were generally of mild or moderate severity and occurred relatively early after treatment initiation (except pneumonitis); incidence tapered off thereafter. EVE dose reduction and interruption (360 and 705 events, respectively) required for AE management were independent of patient age. The median duration of dose interruption was 7 days. Discontinuation of both study drugs because of AEs was higher with EVE + EXE (9%) versus PBO + EXE (3%).ConclusionsMost EVE-associated AEs occur soon after initiation of therapy, are typically of mild or moderate severity, and are generally manageable with dose reduction and interruption. Discontinuation due to toxicity was uncommon. Understanding the time course of class-effect AEs will help inform preventive and monitoring strategies as well as patient education.Trial registration numberNCT00863655.     

Analysis of PTEN and HIF‐1α and correlation with efficacy in patients with advanced renal cell carcinoma treated with temsirolimus versus interferon‐α

BACKGROUND:

Exploratory subgroup analyses from the phase 3 global advanced renal cell carcinoma (ARCC) trial were conducted to determine if baseline levels of the tumor molecular markers PTEN and HIF1 α correlated with efficacy in patients treated with temsirolimus (Torisel) versus interferon‐α (IFN).

METHODS:

Patients in the IFN group received 3 million U (MU) subcutaneously 3x weekly, escalating to 18 MU. Patients in the temsirolimus group received 25 mg intravenously weekly. PTEN and HIF1 α baseline levels were measured in archived tumor specimens by immunohistochemistry.

RESULTS:

There was no correlation between baseline PTEN and HIF1 α levels and treatment effect with respect to overall survival (OS), progression‐free survival, or objective response rate (ORR) in patients with advanced renal cell carcinoma with poor‐risk prognostic factors.

CONCLUSIONS:

The baseline status of the molecular markers PTEN and HIF1 α did not correlate with efficacy in renal cell carcinoma patients treated with temsirolimus versus IFN. Patients demonstrated OS and progression‐free survival benefit when treated with temsirolimus regardless of PTEN and HIF1 α status. Thus, baseline PTEN and HIF‐1 levels may not predict response to temsirolimus. Alternatively, the lack of correlation may be due to the variability in tumor specimens that occurred because of the global nature of the clinical trial. Other markers in the phosphoinositide 3‐kinase (PI3K)/Akt pathway may be of utility as predictors of response to temsirolimus in patients with advanced renal cell carcinoma. Cancer 2009. © 2009 American Cancer Society.     

Safety and efficacy of everolimus (EVE) plus exemestane (EXE) in postmenopausal women with locally advanced or metastatic breast cancer: final results from EVEREXES

Background

This study was conducted to collect clinical safety, tolerability, and efficacy data with the use of everolimus (EVE) combined with exemestane (EXE) in patients with advanced breast cancer (ABC).

Methods

The EVEREXES trial initiated in 2012, provided early access to the first dual blockade treatment with EVE?+?EXE in patients with HR+, HER2???ABC in Asia and other emerging growth countries. Postmenopausal women with HR+, HER2???ABC who had documented recurrence or progression, following a nonsteroidal aromatase inhibitor therapy, were treated with EVE (10 mg/day)?+?EXE (25 mg/day) orally.

Results

A total of 235 patients received?≥?1 dose of study medication. At the end of the study, all patients ceased the treatment. Disease progression (66.0%) was the primary reason of discontinuation. The most common AEs (≥?20%) were stomatitis, decreased appetite, hyperglycemia, rash, aspartate aminotransferase increased, anemia, alanine aminotransferase increased, cough, and fatigue. No new safety concerns were identified in the current study. Median progression-free survival (PFS) in the Asian subset was similar to that of the overall population (9.3 months in both groups). Confirmed overall response rate (ORR) was achieved for 19.6% of the patients. Efficacy of EVE?+?EXE across subgroups (prior CT, line of treatment, and presence of visceral metastases) was maintained.

Conclusion

The safety and efficacy results from EVEREXES trial are consistent to data previously reported in BOLERO-2. These results support that EVE?+?EXE could be a viable treatment option for the postmenopausal women with HR+, HER2???ABC in Asian region.

     

Health‐related quality of life among survivors of aggressive non‐Hodgkin lymphoma

BACKGROUND:

Non‐Hodgkin lymphoma (NHL) is the fifth most common cancer among men and women. Patients with aggressive NHL receive intense medical treatments that can significantly compromise health‐related quality of life (HRQOL). However, knowledge of HRQOL and its correlates among survivors of aggressive NHL is limited.

METHODS:

Self‐reported data on HRQOL (physical and mental function, anxiety, depression, and fatigue) were analyzed for 319 survivors of aggressive NHL. Survivors 2 to 5 years postdiagnosis were selected from the Los Angeles County Cancer Registry. Bivariate and multivariable methods were used to assess the influence of sociodemographic, clinical, and cognitive health‐appraisal factors on survivors' HRQOL.

RESULTS:

After accounting for other covariates, marital status was associated with all HRQOL outcomes (P < .05). Younger survivors reported worse mental function and higher levels of depression, anxiety, and fatigue (P < .01). Survivors who had more comorbid conditions or lacked private health insurance reported worse physical and mental function and higher levels of depression and fatigue (P < .05). Survivors who experienced a recurrence reported worse physical function and higher levels of depression and fatigue (P < .05). With the exception of a nonsignificant association between perceived control and physical function, greater perceptions of personal control and health competence were associated significantly with more positive HRQOL outcomes (P < .01).

CONCLUSIONS:

The current results indicated that survivors of aggressive NHL who are younger, are unmarried, lack private insurance, or experience greater illness burden may be at risk for poorer HRQOL. Cognitive health‐appraisal factors were strongly related to HRQOL, suggesting potential benefits of interventions focused on these mutable factors for this population. Cancer 2013. © 2012 American Cancer Society.     

Impact of oesophagectomy on physical fitness and health‐related quality of life in patients with oesophageal cancer

Although several studies have reported the impact of oesophagectomy on health‐related quality of life (HRQOL), none has objectively assessed its impact on physical fitness. This study aimed to evaluate the impact of oesophagectomy on physical fitness and HRQOL in patients with oesophageal cancer. In this prospective study, we investigated 30 consecutive patients with newly diagnosed resectable oesophageal cancer who were scheduled to receive either neoadjuvant chemotherapy followed by surgery or surgery alone. The primary end‐points were change from baseline in two measures of physical fitness (knee‐extensor muscle strength and 6‐min walking distance) after oesophagectomy. The secondary end‐point was change from baseline in HRQOL measured with the European Organization for the Research and Treatment of Cancer Quality of Life Core Questionnaire with 30 items (EORTC QLQ‐C30). Physical fitness was significantly lower after oesophagectomy than before oesophagectomy (P < 0.001). With regard to HRQOL, there was a significant pre‐ to post‐oesophagectomy change in most of the scales. In the multiple regression analysis, the change in 6‐min walking distance was the only significant variable affecting the change in physical functional score on the EORTC QLQ‐C30 (P = 0.032). In conclusion, oesophagectomy adversely affects physical fitness and HRQOL in patients with oesophageal cancer. Six‐minute walking distance may be a good indicator of HRQOL shortly after oesophagectomy.     

Partnership and outcomes in men with prostate cancer

BACKGROUND:

Being in a supportive relationship may have improved the health‐related quality of life (HRQOL) of men with prostate cancer, if the support was strong and positive. In the current study, the authors sought to examine the impact of partnership status on the mental health of men treated for localized prostate cancer.

METHODS:

Participants had clinically localized prostate cancer and chose treatment with radical prostatectomy (n = 307), external?beam radiotherapy (n = 78), or brachytherapy (n = 91). The authors prospectively assessed subject characteristics and HRQOL outcomes and evaluated associations between partnership outcomes and HRQOL measures. Two multivariate linear regression models were then created, 1 for baseline HRQOL outcomes and 1 for change in HRQOL from baseline to 12 months, with partnership status as the main predictor and subject characteristics as covariates.

RESULTS:

Partnership status was not found to be associated with either baseline physical or mental health, but partnered participants had less bowel bother (P = .02) and a lower fear of recurrence (P = .03) at baseline than did unpartnered subjects. Men with fewer comorbid conditions scored better across almost all baseline HRQOL domains. Primary treatment type was significantly associated with changes in physical HRQOL, with men undergoing radical prostatectomy describing better changes in physical health than those treated with brachytherapy (P = .04) or those receiving external?beam radiotherapy (P ≤ .01).

CONCLUSIONS:

Physical and mental health was found to be comparable in the study cohort of partnered and unpartnered men treated for prostate cancer. The universally high socioeconomic status of the current study cohort may mitigate differences in HRQOL by partnership status. Cancer 2009. © 2009 American Cancer Society.     

Safety and Efficacy of Everolimus With Exemestane vs. Exemestane Alone in Elderly Patients With HER2-Negative,Hormone Receptor–Positive Breast Cancer in BOLERO-2

BackgroundPostmenopausal women with hormone receptor–positive (HR⁺) breast cancer in whom disease progresses or there is recurrence while taking a nonsteroidal aromatase inhibitor (NSAI) are usually treated with exemestane (EXE), but no single standard of care exists in this setting. The BOLERO-2 trial demonstrated that adding everolimus (EVE) to EXE improved progression-free survival (PFS) while maintaining quality of life when compared with EXE alone. Because many women with HR⁺ advanced breast cancer are elderly, the tolerability profile of EVE plus EXE in this population is of interest.Patients and MethodsBOLERO-2, a phase III randomized trial, compared EVE (10 mg/d) and placebo (PBO), both plus EXE (25 mg/d), in 724 postmenopausal women with HR⁺ advanced breast cancer recurring/progressing after treatment with NSAIs. Safety and efficacy data in elderly patients are reported at 18-month median follow-up.ResultsBaseline disease characteristics and treatment histories among the elderly subsets (≥ 65 years, n = 275; ≥ 70 years, n = 164) were generally comparable with younger patients. The addition of EVE to EXE improved PFS regardless of age (hazard ratio, 0.59 [≥ 65 years] and 0.45 [≥ 70 years]). Adverse events (AEs) of special interest (all grades) that occurred more frequently with EVE than with PBO included stomatitis, infections, rash, pneumonitis, and hyperglycemia. Elderly EVE-treated patients had similar incidences of these AEs as did younger patients but had more on-treatment deaths.ConclusionAdding EVE to EXE offers substantially improved PFS over EXE and was generally well tolerated in elderly patients with HR⁺ advanced breast cancer. Careful monitoring and appropriate dose reductions or interruptions for AE management are recommended during treatment with EVE in this patient population.     

Association of progression‐free survival,overall survival,and patient‐reported outcomes by skin toxicity and KRAS status in patients receiving panitumumab monotherapy

BACKGROUND:

The authors explored the association of skin toxicity (ST) severity as measured by patient‐reported ST and Common Terminology Criteria for Adverse Events (CTCAE) grading with efficacy of panitumumab, a fully human antiepidermal growth factor receptor antibody, from a phase 3 metastatic colorectal cancer (CRC) trial.

METHODS:

Patients were randomized to panitumumab plus best supportive care (BSC) vs BSC alone. ST by modified National Cancer Institute CTCAE v3.0 and modified Dermatology Life Quality Index (mDLQI), health‐related quality of life (HRQOL), and CRC symptoms were measured. ST was analyzed using a landmark approach. Associations by KRAS mutational status were also assessed.

RESULTS:

Of 463 patients, 208 of 231 (90%) panitumumab patients and 184 of 232 (79%) BSC patients had ≥1 postbaseline patient‐reported outcome (PRO) assessment. Panitumumab patients with more severe ST had significantly longer overall survival (OS) (grade 2‐4:grade 1; hazard ratio, 0.60; P = .0033). Lower mDLQI scores (<67; more bothersome ST) were associated with longer OS (Cox model, P < .0001). Similar results were observed with progression‐free survival (PFS). An inverse relation between mDLQI and HRQOL scores was observed, suggesting that ST bother correlated with better HRQOL. KRAS and PRO data were available in 363 patients (188 panitumumab; 175 BSC). Longer OS was associated with lower mDLQI scores, regardless of KRAS status. Longer PFS was associated with more severe ST (lower mDLQI scores and higher CTCAE grade ST) in patients with wild‐type (WT) KRAS tumors, but not in patients with mutant KRAS tumors.

CONCLUSIONS:

More severe ST, by both clinical grading and PRO, is associated with better CRC symptoms and HRQOL and with longer OS and PFS among panitumumab‐treated patients. The associations for PFS were more pronounced in patients with WT KRAS tumors. Cancer 2009. © 2009 American Cancer Society.     

Change in health‐related quality of life of newly diagnosed cancer patients,cancer survivors,and controls*

BACKGROUND:

Data from the 1998 Health Outcomes Survey (HOS) of patients who were enrolled in Medicare managed care and follow‐up data from the 2000 HOS resurvey were analyzed to examine changes in health‐related quality of life (HRQOL) of newly diagnosed cancer patients, cancer survivors, and patients without cancer.

METHODS:

In 1998, the HOS was mailed to a random sample of 279,135 beneficiaries, and 167,096 respondents (60%) returned completed surveys. Those who were diagnosed with cancer (22,747) were frequency age‐matched to an equal number of patients with no cancer. In 2000, the HOS was mailed to the same cohort of beneficiaries. Complete data at both baseline and follow‐up were available on 16,850 individuals for inclusion in the current study.

RESULTS:

After 2 years, respondents who had been diagnosed with cancer at baseline continued to have lower scores on all but 3 scales of the 36‐item short‐form HRQOL measure. However, there was no evidence that they were declining any faster than or catching up with noncancer patients. Those who had been newly diagnosed with cancer since the baseline survey had lower mean scale scores than the no‐cancer group on all scales and lower mean scores than the cancer survivors on all subscales except Bodily Pain, Vitality, and Mental Health.

CONCLUSIONS:

This study demonstrated that, after 2 years, cancer survivors continued to have poorer HRQOL than the no‐cancer group. Newly diagnosed cancer patients had poorer quality of life than both the longer term cancer survivors and the no‐cancer group. Cancer 2009. Published 2009 by the American Cancer Society*.     

Impact of diagnosis and treatment of clinically localized prostate cancer on health‐related quality of life for older Americans

BACKGROUND:

Few studies have measured longitudinal changes in health‐related quality of life (HRQOL) among patients with prostate cancer starting before their cancer diagnosis or have provided simultaneous comparisons with a matched noncancer cohort. In the current study, the authors addressed these gaps by providing unique estimates of the effects of a cancer diagnosis on HRQOL accounting for the confounding effects of ageing and comorbidity.

METHODS:

Data from the Surveillance, Epidemiology, and End Results registry were linked with Medicare Health Outcomes Survey (MHOS) data. Eligible patients (n = 445) were Medicare beneficiaries aged ≥65 years from 1998 to 2003 whose first prostate cancer diagnosis occurred between their baseline and follow‐up MHOS. By using propensity score matching, 2225 participants without cancer were identified from the MHOS data. Analysis of covariance models were used to estimate changes in HRQOL as assessed with the Medical Outcomes Study Short Form‐36 survey and the activities of daily living scale.

RESULTS:

Before diagnosis, patients with prostate cancer reported HRQOL similar to that of men without cancer. After diagnosis, men with prostate cancer experienced significant decrements in physical, mental, and social aspects of their lives relative to controls, especially within the first 6 months after diagnosis. For men who were surveyed beyond 1 year after diagnosis, HRQOL was similar to that for controls. However, an increased risk for major depressive disorder was observed among men who received either conservative management or external beam radiation.

CONCLUSIONS:

The current findings illustrated the time‐sensitive nature of decline in HRQOL after a cancer diagnosis and enhanced understanding of the impact of prostate cancer diagnosis and treatment on physical, mental, and social well being among older men. Cancer 2012. © 2012 American Cancer Society.     

Real-World Outcomes of Everolimus and Exemestane for the Treatment of Metastatic Hormone Receptor-Positive Breast Cancer in Patients Previously Treated With CDK4/6 Inhibitors

PurposeEverolimus with exemestane (EVE+EXE) was FDA-approved to treat metastatic hormone receptor-positive breast cancer (mHRBC) based on BOLERO-2. However, none of those patients received prior CDK4/6 inhibitors. The purpose of this study is to evaluate the efficacy of EVE+EXE in mHRBC after CDK4/6 inhibitors.MethodsA retrospective review of patients ≥18 years old with mHRBC treated with EVE+EXE, for ≥30 days, at our institution from January 1, 2012, to April 1, 2020 was conducted. Primary objective was to compare progression free survival (PFS) for EVE+EXE between patients with and without prior exposure to CDK4/6 inhibitors. Secondary outcomes included overall survival and safety.Results192 patients were included in the study (n = 79, prior CDK4/6 inhibitor use; n = 113, no prior CDK4/6 inhibitor use). Baseline patient characteristics were similar between groups. Greater number of prior therapies before EVE+EXE use increased risk of disease progression (P = .017). Patients with prior CDK4/6 inhibitor use had a lower median PFS of 3.8 months (95% CI: 3.4-4.7) vs. 5.4 months (95% CI: 3.9-6.2) for patients without prior CDK4/6 inhibitor use, with a HR for progression of 1.46 (95% CI: 1.08 to 1.97, P = .013). Overall survival between groups was not significantly different.ConclusionPatients who received a prior CDK4/6 inhibitor had a lower median PFS benefit from EVE+EXE compared to those who did not, without differences in overall survival. Although PFS is expected to decrease with subsequent lines of therapy, it is reasonable to use EVE+EXE after CDK4/6 inhibitors in selected patients, recognizing that additional benefit is modest.     

Short-term health-related quality of life and symptom control with docetaxel,cisplatin, 5-fluorouracil and cisplatin (TPF), 5-fluorouracil (PF) for induction in unresectable locoregionally advanced head and neck cancer patients (EORTC 24971/TAX 323)

Background:

The EORTC 24971/TAX 323, a phase III study of 358 patients with unresectable locoregionally advanced squamous cell carcinoma of the head and neck, showed an improved progression-free and overall survival (OS) with less toxicity when docetaxel (T) was added to cisplatin and 5-fluorouracil (PF) for induction and given before radiotherapy (RT). The impact of the addition of docetaxel on patients'' health-related quality of life (HRQOL) and symptoms was investigated.

Methods:

HRQOL was assessed at baseline, at end of cycle 2, and 4, 6, and 9 months after completion of RT using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and the EORTC QLQ Head and Neck Cancer-Specific Module (EORTC QLQ-H&N35). The primary HRQOL scale was global HRQOL per protocol.

Results:

Compliance to HRQOL assessments was 97% at baseline, but dropped to 54% by 6 months. Data were analysed up to 6 months. There was a trend towards improved global HRQOL during the treatment period. At 6 months after the end of RT, global HRQOL was higher in the TPF arm than in the PF arm, but the low compliance does not allow to draw definitive conclusions. Swallowing and coughing problems decreased more in the TPF arm than in the PF arm at the end of cycle 2, but to a limited extent.

Conclusion:

Induction chemotherapy with TPF before RT not only improves survival and reduces toxicity compared with PF but also seems to improve global HRQOL in a more sustainable manner.     

Validity of the Greek EORTC QLQ‐C30 and QLQ‐BR23 for measuring health‐related quality of life in breast cancer patients

KONTODIMOPOULOS N., NTINOULIS K. & NIAKAS D. (2011) European Journal of Cancer Care 20 , 354–361
Validity of the Greek EORTC QLQ‐C30 and QLQ‐BR23 for measuring health‐related quality of life in breast cancer patients The aim of this study was to assess construct validity and internal consistency reliability of the Greek EORTC QLQ‐C30 and QLQ‐BR23 instruments. A sample of female breast cancer patients (n= 105) were self‐administered the QLQ‐C30, QLQ‐BR23 and SF‐36 and questions on treatment and socio‐demographic status. Hypothesised scale structure, reliability (Cronbach's α) and construct validity (convergent, discriminative, concurrent and known‐groups) were assessed. Multitrait scaling confirmed scale structure of the QLQ‐C30 and QLQ‐BR23 with good item convergence (92% and 85%), and discrimination (87% and 84%) rates. Cronbach's α was >0.70 for all but one scale (cognitive functioning). Strength of Spearman's correlations between the QLQ‐C30 and SF‐36 scales assessing similar health‐related quality of life dimensions ranged from 0.25 to 0.64 (P < 0.01). Construct validity was confirmed with satisfactory results for interscale correlations and known‐groups comparisons. QLQ‐BR23 scales showed comparatively low (<0.40) correlations with QLQ‐C30 functional scales, and higher correlations with conceptually related symptom scales. Most QLQ‐C30 and QLQ‐BR23 scales discriminated between pre‐treatment and current treatment patients. The overall psychometric results for the Greek version of the QLQ‐C30 and QLQ‐BR23 confirmed it as a reliable and valid questionnaire for assessing breast cancer‐specific HRQoL in Greece.     

Carbohydrate antigen 19‐9 is a prognostic and predictive biomarker in patients with advanced pancreatic cancer who receive gemcitabine‐containing chemotherapy

BACKGROUND:

Carbohydrate antigen 19‐9 (CA19‐9) is a widely used biomarker in pancreatic cancer. There is no consensus on the interpretation of the change in CA19‐9 serum levels and its role in the clinical management of patients with pancreatic cancer.

METHODS:

Individual patient data from 6 prospective trials evaluating gemcitabine‐containing regimens from 3 different institutions were pooled. CA19‐9 values were obtained at baseline and after successive cycles of treatment. The objective of this study was to correlate a decline in CA19‐9 with outcomes while undergoing treatment.

RESULTS:

A total of 212 patients with locally advanced (n = 50) or metastatic (n = 162) adenocarcinoma of the pancreas were included. Median baseline CA19‐9 level was 1077 ng/mL (range, 15‐492,241 ng/mL). Groups were divided into those levels below (low) or above (high) the median. Median overall survival (mOS) was 8.7 versus 5.2 months (P = .0018) and median time to progression (mTTP) was 5.8 versus 3.7 months (P = .082) in the low versus high groups, respectively. After 2 cycles of chemotherapy, up to a 5% increase versus ≥ 5% increase in CA19‐9 levels conferred an improved mOS (10.3 vs 5.1 months, P = .0022) and mTTP (7.5 vs 3.5 months, P = 0.0005).

CONCLUSIONS:

In patients who have advanced pancreatic cancer treated with gemcitabine‐containing regimens baseline CA19‐9 is prognostic for outcome. A decline in CA19‐9 after the second cycle of chemotherapy is not predictive of improved mOS or mTTP; thus, CA19‐9 decline is not a useful surrogate endpoint in clinical trials. Clinically, a ≥ 5% rise in CA19‐9 after 2 cycles of chemotherapy serves as a negative predictive marker. Cancer 2013. © 2012 American Cancer Society.     

Exemestane versus anastrozole as front-line endocrine therapy in postmenopausal patients with hormone receptor-positive, advanced breast cancer: final results from the Spanish Breast Cancer Group 2001-03 phase 2 randomized trial

BACKGROUND:

Several aromatase inhibitor studies have reported variations in the inhibitory potency of these agents that could lead to differences in clinical outcomes. In the current study, the authors formally evaluated the activity of anastrozole and exemestane in postmenopausal women with hormone‐responsive, advanced breast cancer.

METHODS:

Postmenopausal women who had measurable disease according to Response Evaluation Criteria in Solid Tumors and had not received previous endocrine therapy for advanced breast cancer were randomized to receive either oral exemestane 25 mg daily or oral anastrozole 1 mg daily until they had disease progression. The primary endpoint was the objective response rate (ORR), and secondary endpoints included the clinical benefit rate (CBR), time to progression (TTP), overall survival, and safety. Crossover to the other aromatase inhibitor was permitted at the time of disease progression; ORR, CBR, and TTP after second‐line treatment also were explored.

RESULTS:

In total, 103 patients were enrolled. The median patient age was 71.6 years, 52.4% of patients had visceral disease, and 75.8% of patients had ≥2 disease sites. Half of the patients had received previous tamoxifen, and 60% had received previous chemotherapy. The efficacy observed in the exemestane and anastrozole groups was an ORR of 36.2% and 46%, respectively; a CBR of 59.6% and 68%, respectively, and a TTP of 6.1 months and 12.1 months, respectively. At progression, 28 patients crossed over to the other aromatase inhibitor, including 16 patients who switched to exemestane (CBR, 43.7%; TTP, 4.4 months) and 12 patients who switched to anastrozole (CBR, 8.3%; TTP, 2 months). Both drugs were generally well tolerated, and no study drug‐related serious adverse events were reported.

CONCLUSIONS:

In this phase 2 randomized trial, no significant differences in clinical activity were observed in favor of exemestane to justify a superiority phase 3 trial design in the first‐line setting. Cancer 2012;. © 2011 American Cancer Society.     

Comorbidities are associated with poorer quality of life and functioning and worse symptoms in the 5 years following colorectal cancer surgery: Results from the ColoREctal Well‐being (CREW) cohort study

Objective

More people are living with the consequences of cancer and comorbidity. We describe frequencies of comorbidities in a colorectal cancer cohort and associations with health and well‐being outcomes up to 5 years following surgery.

Methods

Prospective cohort study of 872 colorectal cancer patients recruited 2010 to 2012 from 29 UK centres, awaiting curative intent surgery. Questionnaires administered at baseline (pre‐surgery), 3, 9, 15, 24 months, and annually up to 5 years. Comorbidities (and whether they limit activities) were self‐reported by participants from 3 months. The EORTC QLQ‐C30 and QLQ‐CR29 assessed global health/quality of life (QoL), symptoms, and functioning. Longitudinal analyses investigated associations between comorbidities and health and well‐being outcomes.

Results

At baseline, the mean age of participants was 68 years, with 60% male and 65% colon cancer. Thirty‐two per cent had 1 and 40% had ≥2 comorbidities. The most common comorbidities were high blood pressure (43%), arthritis/rheumatism (32%), and anxiety/depression (18%). Of those with comorbidities, 37% reported at least 1 that limited their daily activities. Reporting any limiting comorbidities was associated with poorer global health/QoL, worse symptoms, and poorer functioning on all domains over 5‐year follow‐up. Controlling for the most common individual comorbidities, depression/anxiety had the greatest deleterious effect on outcomes.

Conclusions

Clinical assessment should prioritise patient‐reported comorbidities and whether these comorbidities limit daily activities, as important determinants of recovery of QoL, symptoms, and functioning following colorectal cancer. Targeted interventions and support services, including multiprofessional management and tailored assessment and follow‐up, may aid recovery of health and well‐being in these individuals.

     

First‐line combination of gemcitabine,oxaliplatin, and L‐asparaginase (GELOX) followed by involved‐field radiation therapy for patients with stage IE/IIE extranodal natural killer/T‐cell lymphoma

BACKGROUND:

Extranodal natural killer/T‐cell lymphoma, nasal type (ENKTL) is a distinct subtype of non‐Hodgkin lymphoma in which the upper aerodigestive tract is the most commonly involved site. To date, optimal treatment strategies and prognosis for patients with ENKTL have not been fully defined.

METHODS:

This prospective study was conducted to evaluate the efficacy and safety profiles of first‐line combined gemcitabine, oxaliplatin, and L‐asparaginase (GELOX) followed by involved‐field radiation therapy for patients with stage IE/IIE ENKTL. The primary endpoints were the complete response rate, the objective response rate, and toxicities. Secondary endpoints were overall survival and progression‐free survival.

RESULTS:

Twenty‐seven patients with newly diagnosed ENKTL were enrolled and completed the entire course of treatment. At the end of treatment, the overall response rate was 96.3%, including 20 patients (74.1%) who attained a complete response and 6 patients (22.2%) who attained a partial response. No patients developed disease progression during therapy. Grade 1 and 2 toxicities were frequent during GELOX, but grade 3 and 4 toxicities were few, and no treatment‐related deaths occurred. At a median follow‐up of 27.37 months, 7 patients (25.9%) experienced disease progression, and 4 of those patients died of disease. The rates of 2‐year overall and progression‐free survival were both 86%, and patients who attained a complete response at the end of treatment had significantly longer progression‐free survival (P = .012) and overall survival (P = .021) than patients who did not attain a complete response.

CONCLUSIONS:

The current results indicated that GELOX followed by involved‐field radiation therapy can be an effective and feasible treatment strategy for patients with stage IE/IIE ENKTL of the upper aerodigestive tract. These results will require further investigation in larger prospective trials. Cancer 2013. © 2012 American Cancer Society.