Patient, family caregiver, and economic outcomes of an integrated screening and novel stepped collaborative care intervention in the oncology setting in the USA (CARES): a randomised, parallel, phase 3 trial.

BACKGROUND: The current standard of care of screening and referring patients for treatment for symptoms, such as depression, pain, and fatigue, is not effective. This trial aimed to test the efficacy of an integrated screening and novel stepped collaborative care intervention versus standard of care for patients with cancer and at least one of the following symptoms: depression, pain, or fatigue. METHODS: This randomised, parallel, phase 3 trial was conducted in 29 oncology outpatient clinics associated with the UPMC Hillman Cancer Center in the USA. Patients (aged ≥21 years) with any cancer type and clinical levels of depression, pain, or fatigue (or all of these) were eligible. Eligible family caregivers were aged 21 years or older and providing care to a patient diagnosed with cancer who consented for this study. Patients were randomly assigned (1:1) to stepped collaborative care or standard of care using a central, permuted block design (sizes of 2, 4, and 6) stratified by sex and prognostic status. The biostatistician, oncologists, and outcome assessors were masked to treatment assignment. Stepped collaborative care was once-weekly cognitive behavioural therapy for 50-60 min from a care coordinator via telemedicine (eg, telephone or videoconferencing). Pharmacotherapy for symptoms might be initiated or changed if recommended by the treatment team or preferred by the patient. Standard of care was screening and referral to a health-care provider for treatment of symptoms. The primary outcome was health-related quality of life in patients at 6 months. Maintenance of the treatment benefits was assessed at 12 months. Participants included in the primary analysis were per intention to treat, which included patients missing one or both follow-up assessments. This trial was registered with ClinicalTrials.gov (NCT02939755). FINDINGS: Between Dec 5, 2016, and April 8, 2021, 459 patients and 190 family caregivers were enrolled. 222 patients were assigned to standard of care and 237 to stepped collaborative care. Of 459 patients, 201 (44%) were male and 258 (56%) were female. Patients in the stepped collaborative care group had a greater 0-6-month improvement in health-related quality of life than patients in the standard-of-care group (p=0·013, effect size 0·09). Health-related quality of life was maintained for the stepped collaborative care group (p=0·74, effect size 0·01). Patients in the stepped collaborative care group had greater 0-6-month improvements than the standard-of-care group in emotional (p=0·012), functional (p=0·042), and physical (p=0·033) wellbeing. No adverse events were reported by patients in either group and deaths were considered unrelated to the study. INTERPRETATION: An integrated screening and novel stepped collaborative care intervention, compared with the current standard of care, is recommended to improve health-related quality of life. The findings of this study will advance the implementation of guideline concordant care (screening and treatment) and has the potential to shift the practice of screening and treatment paradigm nationwide, improving outcomes for patients diagnosed with cancer. FUNDING: US National Cancer Institute.

Predictors and Consequences of Cancer and Non-Cancer-Related Pain in Those Diagnosed with Primary and Metastatic Cancers.

OBJECTIVES: The aims of the study were to (1) describe types of pain in cancer patients, (2) examine the predictors and consequences of pain, (3) investigate the association between type of pain and survival, and (4) examine potential biological mediators of pain and survival. METHODS: This was a secondary analysis of baseline data from patients diagnosed with cancer. Patients answered questionnaires that assessed sociodemographic characteristics, pain, depression, sleep, and fatigue. Blood was collected and cytokine assays were performed. Analysis of variance, Kaplan-Meier, and Cox regression survival analyses were used to test the aims. RESULTS: Of the 779 patients diagnosed with cancer, the mean age was 63.5 years, 57.8% male, and 90.6% White. Of those who reported pain (total 70.3%), 46.5% stated their pain was cancer-related while 53.5% stated their pain was non-cancer-related. While both cancer and non-cancer-related pain was associated with depressive symptoms, fatigue, and sleep duration, those with cancer-related pain had significantly higher rates of depressive symptoms (F(1,516) = 21.217, p < 0.001) and fatigue (F(1,516) = 30.973, p < 0.001) but not poorer sleep (F(1,497) = 0.597, p = 0.440). After adjusting for sociodemographic, disease-related characteristics, depression, sleep duration, and morphine milligram equivalent, patient reports of cancer-related pain were significantly associated with poorer survival (HR = 0.646, 95% CI = 0.459-0.910, p = 0.012) compared to those with non-cancer-related pain, which was not associated with survival (HR = 1.022, 95% CI = 0.737-1.418, p = 0.896). Cytokines did not significantly mediate the link between pain and survival. CONCLUSION: While nearly half of the pain reported was cancer-related, both types of pain resulted in greater symptom burden, but only cancer-related pain was associated with survival.

The benefits and consequences of the COVID-19 pandemic for patients diagnosed with cancer and their family caregivers.

BACKGROUND: The objectives of this study were to examine benefits and consequences of the COVID-19 pandemic for patients diagnosed with cancer and their family caregivers. METHODS: A 23-item questionnaire assessing COVID-19-related issues, the Patient Health Questionnaire-2, Generalized Anxiety Disorder-2, Pittsburgh Sleep Quality Index, and the Perceived Stress Scale (PSS)-4 were administered to patients diagnosed with cancer and their family caregivers. RESULTS: Of the 161 patients and 78 caregivers who participated, 38.1% and 32.8 were male, 95% and 84.6% Caucasian, and the mean age was 66 and 64.6 years, respectively. A total of 16.5% and 15.2% reported depressive symptoms, 18.4% and 19% reported anxiety; 35.5% and 26.6% reported poor sleep quality, and 66% and 63.3% scored one standard deviation above the norms for the PSS, respectively. Predictors of poorer patient- and caregiver-reported outcomes included greater loneliness, worry about self or family being infected by the COVID-19, and worsening relationships with family. The fear of COVID-19 led to 20.8% of patients and 24.4% of family caregivers cancelling medical appointments, procedures, and treatments. A total of 52.5% of patients and 53.2% caregivers reported that the pandemic led to benefit finding but these changes were not associated with any of the measured patient- or caregiver-related outcomes. CONCLUSIONS: Psychological functioning for patients and caregivers was similar to that of pre-pandemic levels, however the decrease in health care utilization secondary to fear of COVID-19 was notable. While there were many negative effects of the pandemic, the majority of patients and caregivers reported some benefit to the pandemic.

The next generation of collaborative care: The design of a novel web-based stepped collaborative care intervention delivered via telemedicine for people diagnosed with cancer.

BACKGROUND: The NIH consensus statement on cancer-related symptoms concluded the most common and debilitating were depression, pain and fatigue [1-6]. Although the comorbidity of these symptoms is well known and may have similar underlying biological mechanisms no intervention has been developed to reduce these symptoms concurrently. The novel web-based stepped collaborative care intervention delivered by telemedicine is the first to be tested in people diagnosed with cancer. METHODS: We plan to test a web-based stepped collaborative care intervention with 450 cancer patients and 200 caregivers in the context of a randomized controlled trial. The primary endpoint is quality of life with other primary outcomes including patient-reported depression, pain, fatigue. Secondary outcomes include patient serum levels of pro-inflammatory cytokines and disease progression. We also will assess informal caregiver stress, depression, and metabolic abnormalities to determine if improvements in patients' symptoms also relate to improvement in caregiver outcomes. RESULTS: The trial is ongoing and a total of 382 patients have been randomized. Preliminary analyses of the screening tools used for study entry suggest that Center for Epidemiological Studies-Depression (CESD) scale has good sensitivity and specificity (0.81 and 0.813) whereas the scale used to assess pain (0.47 and 0.91) and fatigue (0.11 and 0.91) had poor sensitivity but excellent specificity. Using the AUROC, the best cut point for the CES-D was 19, for pain was 4.5; and for fatigue was 2.5. Outcomes not originally proposed included health care utilization and healthcare charges. The first 100 patients who have been followed a year post-treatment, and who were less than 75 years and randomized to the web-based stepped collaborative care intervention, had lower rates of complications after surgery [χ2 = 5.45, p = 0.02]. For patients who survived 6 months or less and were randomized to the web-based stepped collaborative care intervention, had lower rates of 90-day readmissions when compared to patients randomized to the screening and referral arm [χ2 = 4.0, p = 0.046]. Patients randomized to the collaborative care intervention arm had lower overall health care activity-based costs of $16,758 per patient per year when compared to the screening and referral arm. DISCUSSION: This novel web-based stepped stepped collaborative care intervention, delivered via telemedicine, is expected to provide a new strategy to improve the quality of life in those diagnosed with cancer and their caregivers. TRIAL REGISTRATION: ClinicalTrials.govNCT02939755.

SWOG S1400A (NCT02154490): A Phase II Study of Durvalumab for Patients With Previously Treated Stage IV or Recurrent Squamous Cell Lung Cancer (Lung-MAP Sub-study).

INTRODUCTION: The objective of the Lung-MAP sub-study S1400A was to evaluate the response rate to durvalumab, an anti-programmed death-ligand 1 (PD-L1) antibody, in patients with squamous non-small-cell lung cancer (SqNSCLC). PATIENTS AND METHODS: Patients who progressed on at least 1 prior platinum-based chemotherapy were eligible. The study was designed as a phase II/III trial comparing durvalumab with docetaxel but was modified to a single-arm, phase II trial with the primary endpoint of objective response when immunotherapy became an approved treatment. RESULTS: A total of 116 patients were registered to this sub-study; 78 to durvalumab and 38 to docetaxel. Of the 78 patients, 9 were ineligible, and 1 was not evaluable for endpoints. Responses were achieved in 11 patients among the 68 eligible and evaluable patients on durvalumab (overall response rate, 16%; 95% confidence interval [CI], 7%-25%). The disease control rate was 54% (95% CI, 43%-66%), the median overall survival was 11.6 months (95% CI, 10.2-14.3 months), and the median progression-free survival was 2.9 months (95% CI, 2.0-4.0 months). PD-L1 data was available for 43 patients on durvalumab, with 14 (33%) patients who were PD-L1-positive (≥ 25%) and 2 responses (overall response rate, 14%; 95% CI, 0%-33%), the disease control rate was 57% (95% CI, 31%-83%), the median overall survival and progression-free survival were 10.7 months (95% CI, 9.2-14.3 months) and 2.3 months (95% CI, 1.4-4.2 months), respectively. Grade ≥ 3 treatment-related adverse events occurred in 22 (32%) patients on durvalumab, with 6 discontinuing owing to drug-related adverse events (9%; 95% CI, 2%-16%). CONCLUSIONS: Durvalumab shows single-agent activity and toxicities in this sub-group of patients that is comparable with other anti-programmed cell death protein 1/PD-L1 antibodies.

A phase II study of weekly docetaxel in combination with capecitabine in advanced gastric and gastroesophageal adenocarcinomas.

OBJECTIVE: Docetaxel and capecitabine are active agents in advanced gastric and gastroesophageal (GE) carcinomas. This multi-institutional phase II trial evaluates the combination of docetaxel and capecitabine as first- or second-line treatment in patients with advanced gastric and GE adenocarcinomas. METHODS: Patients who had received 1 or no prior chemotherapy regimens were eligible. The chemotherapy regimen consisted of a 21-day cycle with docetaxel 30 mg/m(2) administered on days 1 and 8 and capecitabine 825 mg/m(2) administered twice daily on days 1-14. The primary end point of the study was overall survival (OS). RESULTS: Forty patients were enrolled in the study; 39 received treatment and were evaluable for response and toxicity. The median patient age was 61 years (range 21-84); 8 patients had received prior chemotherapy in the advanced or metastatic setting. Grade 3/4 adverse events occurred in 15 patients (38%), including diarrhea in 5 patients (13%) and hand-foot syndrome in 5 patients (13%). The overall response rate was 32% [95% confidence interval (CI) 16.7-51.4]. The median time to progression and OS were 3.4 months (95% CI 2.7-5.8) and 10.7 months (95% CI 6.1-12.1), respectively. CONCLUSIONS: The regimen of docetaxel and capecitabine is a well-tolerated, easily administered and active outpatient regimen for advanced gastric and GE adenocarcinoma.

Phase II study of docetaxel and gefitinib as second-line therapy in gemcitabine pretreated patients with advanced pancreatic cancer.

BACKGROUND: There is no standard second-line therapy for advanced pancreatic cancer (APC). We evaluated the epidermal growth factor receptor (EGFR) inhibitor gefitinib and docetaxel in a phase II study following gemcitabine failure. METHODS: EGFR overexpression was not required. The initial docetaxel dose was 75 mg/m(2) on day 1 every 21 days. Due to febrile neutropenia in 8 of the first 18 patients, the dose was reduced to 60 mg/m(2). Gefitinib, 250 mg/day orally, was given continuously. RESULTS: Forty-one patients received treatment and were evaluable. Febrile neutropenia was seen in 11 patients (27%), with most events occurring at the docetaxel dose of 75 mg/m(2) (8 of 18 patients). Common treatment-related grade 3/4 toxicities were: fatigue (7%), nausea (7%), diarrhea (5%) and vomiting (2%). There was 1 partial response and stable disease in 19 patients. Time to progression was 1.8 months and median survival was 4.5 months (95% CI 2.9-5.7). CONCLUSION: The tolerability and feasibility of second-line therapy for APC was demonstrated. The combination of gefitinib and docetaxel showed evidence of limited efficacy.

Phase II study of rubitecan, an oral camptothecin in patients with advanced colorectal cancer who have failed previous 5-fluorouracil based chemotherapy.

BACKGROUND: Rubitecan (RFS-2000, 9NC, Orathecin) is an orally bioavailable camptothecin analogue, with evidence of preclinical activity in colon cancer cell lines. We evaluated oral rubitecan (5 days on, 2 days rest per week) on a continuous schedule, in patients with advanced colorectal cancer (CRC), who progressed after 5-fluorouracil based chemotherapy. PATIENTS AND RESULTS: Fourteen eligible patients were treated with rubitecan at 1.5 mg/m2/day on a 5 day/week continuous schedule. Therapy was well tolerated with most adverse events in the mild to moderate category. Grade 3/4 toxicity consisting of anemia, diarrhea and elevated bilirubin was seen in 4 patients. No responses were seen in 13 evaluable patients. Overall median survival (95% confidence interval) was 10.1 (range 3.1-12.6) months, and median time to progression was 2.1 months. CONCLUSIONS: Administration of rubitecan was well tolerated, but this schedule does not appear to have clinical activity in patients with advanced previously treated CRC.