Phase 2 study of pembrolizumab and circulating biomarkers to predict anticancer response in advanced, unresectable hepatocellular carcinoma.

BACKGROUND: Checkpoint inhibitors have shown modest activity in patients with advanced hepatocellular carcinoma (HCC). Herein, the authors report a prospective single-institution clinical/translational phase 2 study of pembrolizumab in patients with advanced HCC and circulating biomarkers closely related to response. METHODS: Pembrolizumab was administered at a dose of 200 mg intravenously every 3 weeks among patients who may have developed disease progression while receiving, were intolerant of, or refused sorafenib. The circulating levels of cytokines, chemokines, programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and PD-L2 were correlated with response, tumor PD-L1 expression, and other clinicopathological features. RESULTS: A total of 29 patients were treated and 28 patients were evaluable for response. The most common laboratory grade 3/4 adverse events were increases in aspartate aminotransferase and/or alanine aminotransferase and serum bilirubin, which for the most part were reversible. In terms of efficacy, one patient achieved a complete response and 8 patients achieved partial responses for an overall response rate of 32%. Four other patients had stable disease. The median progression-free survival was 4.5 months and the median overall survival was 13 months. Response did not correlate with prior sorafenib therapy, PD-L1 tumor staining, or a prior history of hepatitis. Correlative studies revealed that high baseline plasma TGF-ß levels (≥200 pg/mL) significantly correlated with poor treatment outcomes after pembrolizumab. Tumor PD-L1 and plasma PD-L1/PD-1 levels were associated with plasma IFN-γ or IL-10. CONCLUSIONS: Pembrolizumab was found to demonstrate activity in patients with advanced HCC. Toxicity generally was tolerable and reversible. A set of immunological markers in blood plasma as well as PD-L1 staining indicated that baseline TGF-ß could be a predictive biomarker for response to pembrolizumab.

Phase II trial of SOM230 (pasireotide LAR) in patients with unresectable hepatocellular carcinoma.

BACKGROUND: A phase II trial of pasireotide was performed to assess its efficacy and safety in advanced or metastatic hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Patients with advanced HCC and Child-Pugh score ≤7 received pasireotide LAR 60 mg intramuscularly every 28 days. Primary endpoint was disease control rate. Secondary endpoints were time to tumor progression, response rate, treatment-related adverse events, and overall survival. Serum insulin growth factor-1 was measured before and after pasireotide. RESULTS: Twenty patients were treated and evaluable. Eighteen patients (90%) had prior therapy; 16 patients (80%) had multiple therapies. Median age was 65, 75% had Barcelona Clinic Liver Cancer stage C, and 55% had metastatic disease. The main toxicity was hyperglycemia. Rare adverse effects included reversible grade 4 elevation in alanina transaminase/aspartate transaminase in one patient. The best response was stable disease in 9 patients (45%). Median time to tumor progression for the 20 patients was 3 months, and median survival was 9 months. CONCLUSION: Pasireotide had limited clinical benefit as second-line or third-line treatment in patients with advanced or metastatic HCC. Low baseline insulin growth factor-1 level may be indicative when SOM230 treatment may be ineffective, and decreasing levels after treatment may be indicative of disease control.

Levels of symptom burden during chemotherapy for advanced lung cancer: differences between public hospitals and a tertiary cancer center.

PURPOSE: We compared risk factors for high disease- and treatment-related symptom burden over 15 weeks of therapy in medically underserved patients with advanced non-small-cell lung cancer and in patients treated at a tertiary cancer center. PATIENTS AND METHODS: We monitored symptom severity weekly during chemotherapy. Patients were recruited from a tertiary cancer center (n=101) and three public hospitals treating the medically underserved (n=80). We used a composite symptom-severity score and group-based trajectory analysis to form two groups: one with consistently more severe symptoms and another with less severe symptoms. We examined predictors of group membership. RESULTS: Seventy percent of the sample (n=126) reported low symptom-severity levels that decreased during therapy; 30% (n=55) had consistently severe symptoms throughout the study. In multivariate analysis, patients with good performance status being treated in public hospitals were significantly more likely than patients treated at the tertiary cancer center to be in the high-symptom group (odds ratio, 5.6; 95% CI, 2.1 to 14.6; P = .001) and to report significantly higher symptom interference (P = .001). Other univariate predictors of high-symptom group membership included variables associated with being medically underserved (eg, having less education, being single, and being nonwhite). No group differences by ethnicity were observed in the public hospitals. Medically underserved patients were less likely to receive adequate pain management. CONCLUSION: Patients with advanced lung cancer and good performance status treated at public hospitals were more likely than those treated at a tertiary cancer center to experience substantial symptoms during chemotherapy.

Final results of a phase II study of nab-paclitaxel, bevacizumab, and gemcitabine as first-line therapy for patients with HER2-negative metastatic breast cancer.

In order to examine the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-P) in combination with bevacizumab (B) and gemcitabine (G) for the first-line treatment of patients with HER2-negative metastatic breast cancer (MBC). In this single-center, open-label phase II trial, patients with HER2-negative MBC received gemcitabine 1500 mg/m(2), nab-paclitaxel 150 mg/m(2), and bevacizumab 10 mg/kg (each administered intravenously) on days 1 and 15 of a 28-day cycle. The primary end point was progression free survival (PFS); secondary end points were overall response rate (ORR), complete (CR) and partial (PR) response rates, clinical benefit (ORR + stable disease), overall survival (OS), and safety. Thirty patients were enrolled. One patient was ineligible and was not included in analysis. Median PFS was 10.4 months (95% CI: 5.6-15.2 months). ORR was 75.9%, comprising eight (27.6%) CRs and 14 (48.3%) PRs; five patients had stable disease (SD) and two patients (6.9%) had progressive disease (PD) as their best response. The clinical benefit rate was 93.1% (27/29) in the overall group and 84.6% in the triple-negative cohort (11/13). The 18-month survival rate was 77.2% (95% CI: 51.1-90.5%). Eight (27.6%) patients experienced grade 3 or 4 toxicity: grade 4 neutropenic fever (n = 1) and grade 3 infection (n = 6), leukopenia, thrombocytopenia, peripheral neuropathy, seizure, shortness of breath, hematuria, and cardiac tamponade (one each). First-line therapy with nab-P, B, and G demonstrated a median PFS of 10.4 months and a 75.9% ORR with acceptable toxicity; this novel combination warrants investigation in a randomized study.

Pain education for underserved minority cancer patients: a randomized controlled trial.

PURPOSE: Previous studies found that African American and Hispanic cancer patients are at risk for undertreatment of pain. We evaluated the efficacy of a pain education intervention for underserved minority patients. PATIENTS AND METHODS: Ninety-seven underserved African American and Hispanic outpatients with cancer-related pain were enrolled onto a randomized clinical trial of pain management education. The patients in the education group received a culture-specific video and booklet on pain management. The control group received a video and booklet on nutrition. A research nurse met with each patient to review the materials. We measured changes in pain intensity and pain-related interference 2 to 10 weeks after the intervention, as well as changes in quality of life, perceived pain control, functional status, analgesics, and physician pain assessments. RESULTS: Physicians underestimated baseline pain intensity and provided inadequate analgesics for more than 50% of the sample. Although the ratings for pain intensity and pain interference decreased over time for both groups, there was no statistically significant difference between groups. Pain education did not affect quality of life, perceived pain control, or functional status. African American patients in the education but not the control group reported a significant decrease in pain worst ratings from baseline to first follow-up (P < .01), although this decrease was not maintained at subsequent assessments. CONCLUSION: Brief education had limited impact on pain outcomes for underserved minority patients, suggesting that more intensive education for patients and interventions for physicians are needed.

Cancer pain management among underserved minority outpatients: perceived needs and barriers to optimal control.

BACKGROUND: Minority patients with cancer are at risk for undertreatment of cancer-related pain. Most studies of patient-related barriers to pain control have surveyed primarily non-Hispanic Caucasian patients. The purpose of the current study was to explore barriers to optimal pain management among African-American and Hispanic patients with cancer through the use of structured patient interviews. Structured interviews allowed the authors to probe for previously unidentified barriers to pain management in these populations. METHODS: Thirty-one socioeconomically disadvantaged minority patients with cancer (14 African-American patients and 17 Hispanic patients) who had cancer-related pain completed structured interviews that assessed three main content areas: information and communication regarding cancer pain, treatment of cancer pain, and the meaning of cancer pain. RESULTS: The African-American and Hispanic patients reported severe pain and many concerns about pain management. The majority of patients in both ethnic groups expressed a belief in stoicism and concerns about possible addiction to opioid medications and the development of tolerance. The patients described their physicians as the most frequent and trusted source of information about cancer pain. However, patients also reported difficulties with communication and a reluctance to complain of pain. CONCLUSIONS: The reported barriers to pain management indicate that socioeconomically disadvantaged African-American and Hispanic patients can benefit from educational interventions on cancer pain that dispel myths about opioids and teach patients to communicate assertively about their pain with their physicians and nurses.