Avelumab alone or in combination with chemotherapy versus chemotherapy alone in platinum-resistant or platinum-refractory ovarian cancer (JAVELIN Ovarian 200): an open-label, three-arm, randomised, phase 3 study.

BACKGROUND: Most patients with ovarian cancer will relapse after receiving frontline platinum-based chemotherapy and eventually develop platinum-resistant or platinum-refractory disease. We report results of avelumab alone or avelumab plus pegylated liposomal doxorubicin (PLD) compared with PLD alone in patients with platinum-resistant or platinum-refractory ovarian cancer. METHODS: JAVELIN Ovarian 200 was an open-label, parallel-group, three-arm, randomised, phase 3 trial, done at 149 hospitals and cancer treatment centres in 24 countries. Eligible patients were aged 18 years or older with epithelial ovarian, fallopian tube, or peritoneal cancer (maximum of three previous lines for platinum-sensitive disease, none for platinum-resistant disease) and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1:1) via interactive response technology to avelumab (10 mg/kg intravenously every 2 weeks), avelumab plus PLD (40 mg/m2 intravenously every 4 weeks), or PLD and stratified by disease platinum status, number of previous anticancer regimens, and bulky disease. Primary endpoints were progression-free survival by blinded independent central review and overall survival in all randomly assigned patients, with the objective to show whether avelumab alone or avelumab plus PLD is superior to PLD. Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02580058. The trial is no longer enrolling patients and this is the final analysis of both primary endpoints. FINDINGS: Between Jan 5, 2016, and May 16, 2017, 566 patients were enrolled and randomly assigned (combination n=188; PLD n=190, avelumab n=188). At data cutoff (Sept 19, 2018), median duration of follow-up for overall survival was 18·4 months (IQR 15·6-21·9) for the combination group, 17·4 months (15·2-21·3) for the PLD group, and 18·2 months (15·8-21·2) for the avelumab group. Median progression-free survival by blinded independent central review was 3·7 months (95% CI 3·3-5·1) in the combination group, 3·5 months (2·1-4·0) in the PLD group, and 1·9 months (1·8-1·9) in the avelumab group (combination vs PLD: stratified HR 0·78 [repeated 93·1% CI 0·59-1·24], one-sided p=0·030; avelumab vs PLD: 1·68 [1·32-2·60], one-sided p>0·99). Median overall survival was 15·7 months (95% CI 12·7-18·7) in the combination group, 13·1 months (11·8-15·5) in the PLD group, and 11·8 months (8·9-14·1) in the avelumab group (combination vs PLD: stratified HR 0·89 [repeated 88·85% CI 0·74-1·24], one-sided p=0·21; avelumab vs PLD: 1·14 [0·95-1·58], one-sided p=0·83]). The most common grade 3 or worse treatment-related adverse events were palmar-plantar erythrodysesthesia syndrome (18 [10%] in the combination group vs nine [5%] in the PLD group vs none in the avelumab group), rash (11 [6%] vs three [2%] vs none), fatigue (ten [5%] vs three [2%] vs none), stomatitis (ten [5%] vs five [3%] vs none), anaemia (six [3%] vs nine [5%] vs three [2%]), neutropenia (nine [5%] vs nine [5%] vs none), and neutrophil count decreased (eight [5%] vs seven [4%] vs none). Serious treatment-related adverse events occurred in 32 (18%) patients in the combination group, 19 (11%) in the PLD group, and 14 (7%) in the avelumab group. Treatment-related adverse events resulted in death in one patient each in the PLD group (sepsis) and avelumab group (intestinal obstruction). INTERPRETATION: Neither avelumab plus PLD nor avelumab alone significantly improved progression-free survival or overall survival versus PLD. These results provide insights for patient selection in future studies of immune checkpoint inhibitors in platinum-resistant or platinum-refractory ovarian cancer. FUNDING: Pfizer and Merck KGaA, Darmstadt, Germany.

Health care improvement and survivorship priorities of colorectal cancer survivors: findings from the PORTAL colorectal cancer cohort survey.

PURPOSE: Few population-level surveys have explored patient-centered priorities for improving colorectal cancer survivors' care. Working with patients, we designed a survey to identify care improvement and survivorship priorities. METHODS: We surveyed a random sample of 4000 patients from a retrospective, population-based cohort of colorectal cancer survivors diagnosed during 2010-2014. The survey included two multiple response questions: "What would you have changed about your cancer diagnosis and treatment experience?" and "What are your biggest health or lifestyle concerns (other than having cancer) since being diagnosed?" Multivariable regression identified characteristics associated with endorsement of health care experience and survivorship concerns. RESULTS: Survey response rate was 50.2% (2000/3986). Fifty-three percent reported at least one unmet need, most commonly for more information about life after treatment (26.7%). Survivors of rectal cancer reported more needs than respondents with colon cancer; persons of color reported more needs than non-Hispanic whites; individuals without high school diplomas reported more needs than individuals with more education. Fear of recurrence was the most common health/lifestyle concern (58.9%). Respondents under age 65 reported nearly all health/lifestyle concerns more often than respondents over age 74. Rectal cancer survivors reported more concerns about activity limitation, changes, and body function and appearance than colon cancer survivors. Persons of color were more likely to report financial concerns than non-Hispanic whites. CONCLUSIONS: The greatest needs for intervention are among survivors of rectal cancer, survivors of minority racial/ethnic background, and survivors of younger age. Survivors with low educational attainment and those with higher stage disease could also benefit.

Association between gelatin-thrombin matrix use and abscesses in women undergoing pelvic surgery.

OBJECTIVE: To assess the association between the use of gelatin-thrombin matrix and the development of pelvic abscess during hysterectomy as well as factors associated with surgeons' use of this product. METHODS: Data for patients undergoing hysterectomy for obstetric-gynecologic pathology were abstracted from databases at a tertiary hospital between 2009 and 2012. Open and minimally invasive hysterectomies were included and vaginal hysterectomies were excluded. Blood loss, surgery type, comorbidities, abscess formation, and use of gelatin-thrombin matrix were examined. Abscess was defined as a walled-off fluid collection (documented with computed tomography scan) with fever (greater than 38°C) or leukocytosis (greater than 11,000/microliter). Standard statistical models were used. RESULTS: Of the 413 patients identified, 213 (51%) underwent surgery for malignancy. Gelatin-thrombin matrix was used in 166 patients (40%). The overall rate of abscess was low (3%). In bivariate analyses, blood loss greater than 500 mL (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.1-12.9, P=.021], ascites (OR 6.5, 95% CI 1.6-26.1, P=.023), drain placement (OR 4.5, 95% CI 1.3-15.1, P=.009), and gelatin-thrombin matrix use (OR 7.0, 95% CI 1.5-32.9, P=.009) were significantly associated with abscess formation. Multivariate logistic regression revealed that only gelatin-thrombin matrix use predicted the development of pelvic abscess (OR 7.0, 95% CI 1.5-32.9, P=.013). CONCLUSION: We found that gelatin-thrombin matrix use was associated with an increased risk of pelvic abscess. Although these products are important in the setting of bleeding, these data suggest that the liberal use of sealants is not without risk. LEVEL OF EVIDENCE: III.

Risk-reducing salpingectomy as preventative strategy for pelvic serous cancer.

The systemic failure to detect early-stage ovarian cancer may be attributed to a significant amount of pelvic serous cancers arising from the fallopian tube rather than the ovarian surface epithelium. This article reviews the possibility of applying risk-reducing salpingectomy as a new paradigm for the prevention of pelvic serous cancer in both high- and low-risk women.

Relationship between aerobic capacity, injury risk and tenure for new-hire delivery drivers.

Over a 2-year study period, aerobic capacity was measured at time of hire for 1419 delivery drivers. Injury experience and tenure were then monitored for these new-hires during that same period. Number of strain injuries, time to first strain and time to termination were regressed on aerobic capacity adjusting for tenure. Statistically significant, monotonically changing relationships were found for all three outcome variables. A unit increase in aerobic capacity was predicted to result in a 3.7% decrease in injury rate and a 1.1% decrease in risk of termination. When age was included in the model for time to termination, aerobic capacity was no longer a significant predictor. The findings regarding injury experience and aerobic capacity support National Institute for Occupational Safety and Health recommendations that individuals should work at no more than 21-30% of their aerobic capacity. STATEMENT OF RELEVANCE: Knowledge of the nature of the relationship between aerobic capacity, injury experience and retention allows the ergonomist to determine whether there is a point of diminishing returns in intervention effectiveness for higher levels of aerobic capacity.