No adjuvant treatment has been established for patients who remain at high risk for recurrence after neoadjuvant chemoradiotherapy and surgery for esophageal or gastroesophageal junction cancer.
We ...conducted CheckMate 577, a global, randomized, double-blind, placebo-controlled phase 3 trial to evaluate a checkpoint inhibitor as adjuvant therapy in patients with esophageal or gastroesophageal junction cancer. Adults with resected (R0) stage II or III esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy and had residual pathological disease were randomly assigned in a 2:1 ratio to receive nivolumab (at a dose of 240 mg every 2 weeks for 16 weeks, followed by nivolumab at a dose of 480 mg every 4 weeks) or matching placebo. The maximum duration of the trial intervention period was 1 year. The primary end point was disease-free survival.
The median follow-up was 24.4 months. Among the 532 patients who received nivolumab, the median disease-free survival was 22.4 months (95% confidence interval CI, 16.6 to 34.0), as compared with 11.0 months (95% CI, 8.3 to 14.3) among the 262 patients who received placebo (hazard ratio for disease recurrence or death, 0.69; 96.4% CI, 0.56 to 0.86; P<0.001). Disease-free survival favored nivolumab across multiple prespecified subgroups. Grade 3 or 4 adverse events that were considered by the investigators to be related to the active drug or placebo occurred in 71 of 532 patients (13%) in the nivolumab group and 15 of 260 patients (6%) in the placebo group. The trial regimen was discontinued because of adverse events related to the active drug or placebo in 9% of the patients in the nivolumab group and 3% of those in the placebo group.
Among patients with resected esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy, disease-free survival was significantly longer among those who received nivolumab adjuvant therapy than among those who received placebo. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 577 ClinicalTrials.gov number, NCT02743494.).
Background Although current therapy for patients with early-stage squamous cell carcinoma of the head and neck (SCCHN) is potentially curative, the recurrence rate is high. Patients with recurrent or ...metastatic (R/M) SCCHN have a poor prognosis and substantial disease burden, including impaired health-related quality of life (HRQoL), productivity loss and indirect costs, such as need for caregiver support. The aim of this study was to characterize the impact of R/M SCCHN and its first-line treatment on patient and caregiver quality of life, daily activities and work productivity using real-world evidence from Europe. Methods This was a multicentre retrospective study of patients with R/M SCCHN in France, Germany, Italy, Spain and the United Kingdom incorporating patient and caregiver surveys, and a physician-reported medical chart review, conducted between January and May 2019. Patients aged 18 or over with a physician confirmed diagnosis R/M SCCHN completed four validated measures of disease activity and its impact on quality of life and work productivity, while caregivers also completed questionnaire to assess the burden of providing care. Physicians provided data for clinical characteristics, patient management, testing history and treatment patterns. Results A total of 195 medical/clinical oncologists provided data for 937, predominantly male (72%) patients, with almost half of patients aged over 65 years. The most frequently reported symptoms were fatigue (43%), weight loss (40%), pain (35%) and difficulty swallowing (32%). The EXTREME regimen was the most common first line therapy in over half of patients, who reported moderate or extreme pain/discomfort, and anxiety/depression, and problems with self-care resulting in a diminished health status compared with the general population. Only 14% were employed with high absenteeism or presenteeism, and over half of patients had a caregiver for whom the burden of care was substantial. Conclusion Our results provide real-world insight into the multi-faceted burden associated with R/M SCCHN. The combination of poor HRQoL and the impairment in daily activities, social life and employment illustrates the wider impact of R/M SCCHN on patients and their caregivers, and highlights a need for novel 1 L treatment regimens to improve the humanistic and productivity burdens of this cancer. Keywords: Squamous cell carcinoma of the head and neck, SCCHN, First line treatment, Platinum-eligible, Quality of life, EQ-5D, FACT-H&N, WPAI, Europe
Background
Glioblastoma is an incurable disease with a poor prognosis. For caregivers of people with glioblastoma, the burden of care can be high. Patients often present with different clinical ...characteristics, which may impact caregiver burden in different ways. This study aimed to evaluate associations between patient clinical characteristics and caregiver burden/quality of life (QoL).
Methods
Caregiver–patient dyads were enrolled at 7 academic cancer centers in the United States. Eligible caregiver participants were self-reported as the primary caregiver of an adult living with glioblastoma and completed a caregiver burden survey. Eligible patients were age ≥ 18 years at glioblastoma diagnosis and alive when their respective caregiver entered the study, with the presence of cognitive dysfunction confirmed by the caregiver. Data were analyzed with descriptive statistics and multivariable analyses.
Results
The final cohort included 167 dyads. Poor patient performance status resulted in patient difficulty with mental tasks, more caregiving tasks, and increased caregiving time. Language problems were reported in patients with left-sided lesions. Patient confusion was negatively associated with all caregiver domains: emotional health, social health, general health, ability to work, confidence in finances, and overall QoL. Better caregiver QoL was observed in patients with frontal lobe lesions versus non-frontal lobe lesions.
Conclusion
This study reinforced that patient performance status is a critical clinical factor that significantly affects caregiver burden, caregiving tasks, and caregiver time. Additionally, patient confusion affects multiple facets of caregiver burden/QoL. These results could be used to support guided intervention for caregiver support, customized to the patient experience.
Investigate real-world outcomes and healthcare utilization of patients with glioblastoma multiforme (GBM) related to O
-methylguanine DNA methyltransferase (MGMT) promoter testing and methylation.
US ...Oncology Network data were analyzed for patients receiving first-line (1L) treatment for GBM.
Most patients received 1L radiation with temozolomide. Unadjusted median overall survival (OS) was higher in tested versus untested (median:18.1 vs 11.8 months) and in methylated versus unmethylated (median: 25.5 vs 12.4 months). Untested status, unmethylated MGMT and older age were associated with reduced OS and longer 1L treatment with increased OS. Similar findings were observed for progression-free survival. Utilization was similar between cohorts.
In community oncology practices, MGMT methylation and testing were predictive of better survival in GBM.
We studied the characteristics and survival of patients with newly diagnosed glioblastoma multiforme (GBM) in community-based oncology practices. These patients had received temozolomide and radiotherapy with surgery, which is the standard of care for GBM. We were interested in how patient survival was related to methylation of the O
-methylguanine DNA methyltransferase (MGMT) promoter. The study showed that patients with methylated versus unmethylated MGMT GBM survived longer. However, patients who were tested for methylation, whether MGMT was methylated or not, also survived longer. This may be because patients who get tested also get better care in general.
Kaplan–Meier analysis showed that patients with methylated MGMT GBM had better overall survival compared with unmethylated MGMT (median: 25.5 vs 12.4 months). However, so did patients who were tested for MGMT methylation compared with those untested for MGMT methylation (median: 18.1 vs 11.8 months).
To evaluate disease-free survival (DFS) as a surrogate endpoint for overall survival (OS) using aggregate-level data from resectable esophageal or gastroesophageal junction cancer (EC/GEJC) trials ...assessing therapies in (neo)adjuvant and perioperative settings.
A systematic literature review was conducted to identify trials reporting OS and DFS, or compatible progression-free survival (PFS). Bivariate random-effects meta-analysis was used to estimate correlation between the treatment effects on DFS/PFS and OS, and weighted linear regression models assuming trial sample sizes as weights were used to estimate surrogacy equations. The primary analysis consisted of trials across all treatment settings, and secondary analysis consisted of trials only in the adjuvant setting. Leave-one-out cross-validation (LOOCV) was performed to measure the stability and predictive accuracy of the surrogacy equations while surrogate threshold effects (STE)-the minimum treatment effect on DFS/PFS that would translate into a positive OS benefit-were derived to measure their usefulness.
The primary analysis included 26 trials. The estimated correlation coefficient between the hazard ratio (HR) of DFS/PFS (HR
) and HR of OS (HR
) was 0.83 (95% confidence interval CI: 0.70-0.90). The estimated surrogacy equation was log(HR
) = 0.80 × log(HR
) with a corresponding STE of 0.82. Reported HR
was within the 95% prediction interval of the predicted HR
from the model for more than 95% of the trials in the LOOCV, indicating a valid model. Secondary analysis included 7 trials with an estimated correlation coefficient of 0.76 (95% CI: 0.18-0.95). Through LOOCV, the surrogacy equation in the adjuvant setting was deemed valid.
Our meta-analysis suggests that HR
-where DFS/PFS is defined as time from resection to disease recurrence (local, locoregional, or distant) or death-is correlated to HR
, and a valid and useful surrogate predictor for HR
in the neoadjuvant, perioperative, or adjuvant settings.
Background
In the Phase‐III clinical trial, CheckMate 141, nivolumab significantly improved survival versus standard of care in patients with platinum‐refractory recurrent/metastatic squamous cell ...carcinoma of the head and neck (R/M SCCHN).
Methods
This pooled analysis investigated the real‐world effectiveness of nivolumab, following prior platinum‐based therapy, in patients with R/M SCCHN from the United States (US) Flatiron Health database and German HANNA prospective observational study.
Results
Overall, 782 patients (56% US; 44% Germany) were included. Median overall survival (OS) was 8.71 months, and progression‐free survival was 4.11 months. Eastern Cooperative Oncology Group Performance Status 0 or 1, platinum sensitivity, and older age were associated with longer OS, in which number of prior lines of therapy had no significant effect.
Conclusion
These findings demonstrate survival benefits of nivolumab in patients with R/M SCCHN in the real‐world setting. The observed real‐world effectiveness of nivolumab aligns with the efficacy of nivolumab in CheckMate 141.
Introduction
Squamous cell carcinomas of the head and neck (SCCHN) account for approximately 4% of all malignancies and are associated with high morbidity and poor prognosis. For patients who are not ...eligible for surgery or radiotherapy, treatment options are limited, especially for those with recurrent or metastatic (R/M) disease. Current European guidelines recommend first-line (1L) treatment with palliative chemotherapy, using biologic or platinum-based regimens. In the absence of new clinical trials in SCCHN, the use of real-world data has facilitated the assessment of treatment patterns and outcomes in different healthcare systems. This study reports on the 1L treatment of platinum-eligible patients with R/M SCCHN in Italy and Spain.
Methods
A point-in-time survey of the management of patients with R/M SCCHN was completed by clinical oncologists in Italy and Spain between October 2018 and February 2019. Patient demographics and clinical characteristics were obtained by retrospective chart review, whilst participating patients self-reported the impact of their disease on their quality of life (QoL) and well-being.
Results
A total of 436 patients were recruited from Italy (216) and Spain (220). Patient demographics for both countries comprised mostly male patients, aged 65 years in Italy and 63 in Spain on average. The primary site for the SCCHN was the pharynx and 36% of patients had metastatic disease overall. EXTREME or cetuximab-based regimens were the most common treatments administered at 1L (52% in Italy and 78% in Spain). Scores on the FACT-G in both countries were substantially lower than those of the general and other advanced cancer populations, while scores on the EQ-5D were clinically meaningfully lower than local population norms.
Conclusion
Despite 1L treatment of platinum-eligible patients with R/M SCCHN in Italy and Spain following current European guidelines, patients’ QoL remains poor, which highlights the need for alternative treatments that could improve clinical outcomes.
Purpose
This study examined clinical and economic outcomes among patients with advanced hepatocellular carcinoma (HCC) treated with systemic agents by line of therapy.
Methods
Adults with ≥ 2 medical ...claims for primary diagnosed HCC (from January 1, 2008, through September 30, 2015) and ≥ 1 claim for systemic HCC-related therapy were identified in the IBM MarketScan® Research Databases. Continuous enrollment was required 6 months before and 1 month after diagnosis. Patients were categorized into first- (1L) and second-line (2L) treatment cohorts; those receiving sorafenib as 1L were evaluated. Treatment patterns, healthcare resource utilization, costs, and survival during 1L and 2L therapy were measured. Survival was assessed for patients linked to the Social Security Administration Master Death File.
Results
1459 patients, 758 with death data, met the 1L cohort criteria; 163 patients, 87 with death data, later received 2L therapy. 77.1% had 1L sorafenib, alone or in combination. Median 1L treatment duration was 3.0 months; median survival time from start of 1L to death or censor was 6.8 months. There was no predominant 2L agent. Median 2L treatment duration was 3.0 months; median survival time from start of 2L was 9.3 months. Median total healthcare costs per patient per month were $13,297 for 1L (all), $13,471 for 1L (sorafenib), and $11,786 for 2L.
Conclusions
Findings confirm high 1-year mortality for advanced HCC, suggesting a high cost burden. While no 2L therapy was available during this analysis, recently approved 2L agents have the potential to improve survival after sorafenib failure or intolerance.
Aims: In 2016, nivolumab and pembrolizumab were approved for the treatment of squamous cell carcinoma of the head and neck (SCCHN) following progression after initial platinum-based therapy. We ...sought to explore the uptake, effectiveness, and impact on healthcare resource utilization (HRU) and total costs of care pre and post introduction of immuno-oncology (IO) agents.
Materials and Methods: Recurrent/metastatic SCCHN patients were identified from a healthcare claims clearinghouse by selecting patients with a claim for distant metastases or who initiated systemic therapy at least 120 days following discontinuation of platinum-based therapy. Two cohorts were created according to the date of post-platinum therapy (PPT) initiation: pre-IO = 08/01/2014-07/31/2015; post-IO = 08/01/2016-07/31/2017. Treatment patterns and effectiveness (duration of treatment, time to next treatment) during first-line (1 L) PPT, HRU, and costs were compared between propensity-score matched patients from each cohort.
Results: Of 716 patients identified (pre-IO = 265, post-IO = 451) 46.3% of post-IO patients received IO post-platinum. In 229 matched patients 20.0% of the post-IO compared to 10.7% of the pre-IO (p=.02) had at least a 6 month duration of 1 L PPT. Inpatient admissions during 1 L PPT: 34.1% post-IO versus 48.0% pre-IO (p= <.01). PPPM total costs of care in 1 L PPT were significantly greater post-IO ($11,535) compared to pre-IO ($9,054, p=.002). Time to next treatment (from 1 L PPT start) was 6.1 months pre-IO versus 7.4 months post-IO (p=.046).
Limitations: Recurrent SCCHN patients were identified using a validated claims-based algorithm but misclassification may occur. Requiring patients to have received 1 L PPT the pre-IO cohort may be systematically different that the post-IO cohort as pre-IO patients were more likely to have not received further treatment beyond 1 L PPT.
Conclusions: The significant uptake of IO therapy resulted in longer durations of therapy, lower rates of hospitalizations although higher treatment costs. The results suggest IO treatment provides additional clinical benefits to recurrent/metastatic SCCHN patients.
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