Age-related systemic treatment and survival of patients with metachronous metastases from colorectal cancer.

BACKGROUND: Although the spectrum of systemic treatment for metastatic colorectal cancer (mCRC) has widened, there is a paucity of evidence for the feasibility and optimal use of these systemic agents in elderly patients. The present study provides real world data on the age-related systemic treatment and survival of CRC patients with non-resectable metachronous metastases. METHODS: All consecutive patients with non-resectable metastases from primary resected CRC were extracted from the Eindhoven area of the Netherlands Cancer Registry (NCR). Patients receiving palliative systemic therapy were enrolled (n = 385). Systemic treatment and survival were analyzed according to age at diagnosis of metastases. RESULTS: Patients aged ≥75 years more often received first-line single-agent chemotherapy than their younger counterparts (63% vs. 32%, p < .0001). First-line single-agent chemotherapy was often prescribed without additional targeted therapy (78%). Advanced age (≥75 years) was associated with a lower probability of receiving all active cytotoxic agents compared to patients aged <60 years at time of diagnosis of metastases (odds ratio (OR) 0.2, 95% CI 0.10-0.77). In a multivariable Cox regression analysis with adjustment for age and other relevant prognostic factors, the total number of received systemic agents was the only predictor of death (hazard ratio (HR) 0.7, 95% CI 0.61-0.81). CONCLUSION: The beneficial effect of treatment with all active systemic agents on survival (simultaneously or sequentially prescribed) should be taken into account when considering systemic therapy in patients with mCRC. In light of our results, future studies are warranted to clarify the role of potential targeted therapy in elderly mCRC patients, who are often not candidates for combination chemotherapy and treatment with all active cytotoxic agents.

Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer.

BACKGROUND: Fluoropyrimidine-based chemotherapy plus the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab is standard first-line treatment for metastatic colorectal cancer. We studied the effect of adding the anti-epidermal growth factor receptor (EGFR) antibody cetuximab to a combination of capecitabine, oxaliplatin, and bevacizumab for metastatic colorectal cancer. METHODS: We randomly assigned 755 patients with previously untreated metastatic colorectal cancer to capecitabine, oxaliplatin, and bevacizumab (CB regimen, 378 patients) or the same regimen plus weekly cetuximab (CBC regimen, 377 patients). The primary end point was progression-free survival. The mutation status of the KRAS gene was evaluated as a predictor of outcome. RESULTS: The median progression-free survival was 10.7 months in the CB group and 9.4 in the CBC group (P=0.01). Quality-of-life scores were lower in the CBC group. The overall survival and response rates did not differ significantly in the two groups. Treated patients in the CBC group had more grade 3 or 4 adverse events, which were attributed to cetuximab-related adverse cutaneous effects. Patients treated with cetuximab who had tumors bearing a mutated KRAS gene had significantly decreased progression-free survival as compared with cetuximab-treated patients with wild-type-KRAS tumors or patients with mutated-KRAS tumors in the CB group. CONCLUSIONS: The addition of cetuximab to capecitabine, oxaliplatin, and bevacizumab resulted in significantly shorter progression-free survival and inferior quality of life. Mutation status of the KRAS gene was a predictor of outcome in the cetuximab group. (ClinicalTrials.gov number, NCT00208546.)

Health-related quality of life and disease-specific complaints among multiple myeloma patients up to 10 yr after diagnosis: results from a population-based study using the PROFILES registry.

BACKGROUND: This prospective population-based study describes health-related quality of life (HRQOL) and disease-specific complaints of patients with multiple myeloma (MM) up to 10 yr post-diagnosis. METHODS: The Eindhoven Cancer Registry was used to select all patients diagnosed with MM from 1999 to 2010. Patients with MM completed the EORTC QLQ-C30 and EORTC QLQ-MY20 questionnaires at baseline (n = 156; 74% response rate) and 1 yr later (n = 80). The EORTC QLQ-C30 was also completed by an age- and sex-matched normative population (n = 500). RESULTS: Patients with MM reported statistically significant and clinically relevant worse scores on all EORTC QLQ-C30 scales (all P's at least < 0.01) compared to the norm. Also, patients with MM reported a mean decrease (e.g., worsening) between baseline and 1-yr follow-up scores for: quality of life (mean, 68 vs. 55, respectively, P < 0.001; 74% of patients had a deteriorated score), fatigue (33 vs. 39, P < 0.05; 50%), nausea and vomiting (6.3 vs. 13, P < 0.05; 71%), pain (33 vs. 43, P < 0.05; 59%), and dyspnea (17 vs. 33, P < 0.001; 66%). The most bothering symptoms during the past week were tingling hands/feet (32%), back pain (28%), bone aches/pain (26%), pain in arm/shoulder (19%), and feeling drowsy (18%). Also, 37% worried about their future health, 34% thought about their disease, and 21% worried about dying. CONCLUSION: Patients with MM experience a very high symptom burden and low HRQOL. Future studies should focus on possible mechanisms that can predict low HRQOL and high symptom burden in patients with MM and should investigate optimal ways to alleviate these.

Perceptions of involvement in advance care planning and emotional functioning in patients with advanced cancer.

PURPOSE: Advance Care Planning (ACP) is positively associated with the quality of care, but its impact on emotional functioning is ambiguous. This study investigated the association between perceptions of ACP involvement and emotional functioning in patients with advanced cancer. METHODS: This study analyzed baseline data of 1,001 patients of the eQuiPe study, a prospective, longitudinal, multicenter, observational study on quality of care and quality of life in patients with advanced cancer in the Netherlands. Patients with metastatic solid cancer were asked to participate between November 2017 and January 2020. Patients' perceptions of ACP involvement were measured by three self-administered statements. Emotional functioning was measured by the EORTC-QLQ-C30. A linear multivariable regression analysis was performed while taking gender, age, migrant background, education, marital status, and symptom burden into account. RESULTS: The majority of patients (87%) reported that they were as much involved as they wanted to be in decisions about their future medical treatment and care. Most patients felt that their relatives (81%) and physicians (75%) were familiar with their preferences for future medical treatment and care. A positive association was found between patients' perceptions of ACP involvement and their emotional functioning (b=0.162, p<0.001, 95%CI[0.095;0.229]) while controlling for relevant confounders. CONCLUSIONS: Perceptions of involvement in ACP are positively associated with emotional functioning in patients with advanced cancer. Future studies are needed to further investigate the effect of ACP on emotional functioning. TRIAL REGISTRATION NUMBER: NTR6584 Date of registration: 30 June 2017 IMPLICATIONS FOR CANCER SURVIVORS: Patients' emotional functioning might improve from routine discussions regarding goals of future care. Therefore, integration of ACP into palliative might be promising.

Implementation, participation and satisfaction rates of a web-based decision support tool for patients with metastatic colorectal cancer.

OBJECTIVE: To examine implementation and patients' and providers' participation and satisfaction of a newly developed decision support tool (DST) for patients with metastatic colorectal cancer (mCRC) in palliative setting. METHODS: Our DST consisted of a consultation sheet and web-based tailored information for mCRC treatment options. We conducted an implementation trajectory in 11 Dutch hospitals and evaluated implementation, participation and satisfaction rates. RESULTS: Implementation rates fluctuated between 3 and 72 handed out (median:23) consultation sheets per hospital with patients' login rates between 36% and 83% (median:57%). The majority of patients (68%) had (intermediate)-high participation scores. The median time spent using the DST was 38 min (IQR:18-56) and was highest for questions concerning patients' perspective (5 min). Seventy-six% of patients were (very) satisfied. The provider DST rating was 7.8 (scale 1-10) and participation ranged between 25 and 100%. Remaining implementation thresholds included providers' treatment preferences, resistance against shared decision-making and (over)confidence in shared decision-making concepts already in use. CONCLUSION: We implemented a DST with sufficient patient and oncologist satisfaction and high patient participation, but participation differed considerably between hospitals suggesting unequal adoption of our tool. PRACTICE IMPLICATIONS: Requirements for structural implementation are to overcome remaining thresholds and increase awareness for additional decision support.

Everolimus Exposure and Early Metabolic Response as Predictors of Treatment Outcomes in Breast Cancer Patients Treated with Everolimus and Exemestane.

BACKGROUND: Treating breast cancer patients with everolimus and exemestane can be challenging due to toxicity and suboptimal treatment responses. OBJECTIVE: We investigated whether everolimus exposure and early metabolic response are predictors for toxicity and effectiveness in these patients. PATIENTS AND METHODS: We performed pharmacokinetic assessments 14 and 35 days after starting treatment. [18F]fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) was performed at baseline, and 14 and 35 days after the start of the therapy. We recorded toxicity, defined as dose interventions within 3 months, and progression-free survival (PFS). RESULTS: Among 44 evaluable patients, the geometric mean (GM) Ctrough was higher in patients with toxicity compared to patients without (17.4 versus 12.3 µg/L (p = 0.02)). The optimal cut-off value to predict toxicity was Ctrough > 19.2 µg/L. GM Ctrough of patients with and without progressive disease (PD) within 3 months was not significantly different (12.0 versus 15.2 µg/L (p = 0.118)). In 28 evaluable patients, PD within 3 months could best be predicted using the percentage decrease in peak standardized uptake value normalized by lean body mass of the lesion with highest FDG uptake (SULpeak high) at day 14. Patients with <11% versus >11% decrease in SULpeak high at day 14 had a median PFS of 90 days versus 411 days, respectively (p = 0.0013) and more frequently had PD within 3 months: 70 vs 11%, respectively. CONCLUSIONS: Our results show that everolimus toxicity is related to everolimus Ctrough. No relation was observed between everolimus exposure and treatment effectiveness. An early FDG-PET can identify patients at high risk of nonresponse. These results warrant further validation. Clinicaltrials.gov identifier: NCT01948960.