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Background: Improving oral anticancer agent (OAA) initiation and adherence is the important quality‐of‐care issues, particularly since one fourth of anticancer agents being developed will be administered orally. Our objective was to identify provider‐ and patient‐level characteristics associated with OAA initiation and adherence among individuals with metastatic renal cell carcinoma (mRCC). Methods: We used state cancer registry data linked to multi‐payer claims data to identify patients with mRCC diagnosed in 2004–2015. Provider data were obtained from North Carolina Health Professions Data System and the National Plan & Provider Enumeration System. We estimated risk ratios (RRs) and corresponding 95% confidence limits (CLs) using modified Poisson regression to evaluate factors associated with OAA initiation and adherence. Results: Among the 207 (out of 687) patients who initiated an OAA following mRCC diagnosis and survived 90 days, median proportion of days covered was 0.91. Patients with a modal provider specializing in hematology/medical oncology were much more likely to initiate OAAs than those seen by other specialties. Additionally, patients with a female provider were more likely to initiate OAAs than those with a male provider. Compared to patients treated by providers practicing in both urban and rural areas, patients with providers practicing solely in urban areas were more likely to initiate OAAs, after controlling for patient‐level factors (RR = 1.37; 95% CL: 1.09–1.73). Medicare patients were less likely to be adherent than those with private insurance (RR = 0.61; 95% CL: 0.42–0.87). Conclusions: Our results suggest that provider‐ and patient‐level factors influence OAA initiation in patients with mRCC but only insurance type was associated with adherence. [ABSTRACT FROM AUTHOR]

Introduction: Two separate antiangiogenic tyrosine kinase inhibitors (TKIs) and immunotherapy (IO) combinations are FDA‐approved as front‐line treatment for metastatic renal cell carcinoma (mRCC). Little is known about off‐protocol and post‐front‐line experience with combination TKI–IO approaches. Methods: We conducted a retrospective analysis of mRCC patients who received combination TKI–IO post‐first‐line therapy between November 2015 and January 2019 at MD Anderson Cancer Center and Duke Cancer Institute. Chart review detailed patient characteristics, treatments, toxicity, and survival. Independent radiologists, blinded to clinical data, assessed best radiographic response using RECIST v1.1. Results: We identified 48 mRCC patients for inclusion: median age 65 years, 75.0% clear cell histology, 68.8% IMDC intermediate risk, and median two prior systemic therapies. TKI–IO combinations included nivolumab–cabozantinib (N +C; 24 patients), nivolumab–pazopanib (N+P; 13), nivolumab–axitinib (6), nivolumab–lenvatinib (2), and nivolumab–ipilimumab–cabozantinib (3). The median progression‐free survival was 11.6 months and the median overall survival was not reached. Response data were available in 45 patients: complete response (CR; n = 3, 6.7%), partial response (PR; 20, 44.4%), stable disease (SD; 19, 42.2%), and progressive disease (3, 6.7%). Overall response rate was 51% and disease control rate (CR+PR+SD) was 93%. Only one patient had a grade ≥3 adverse event. Conclusion: To our knowledge, this is the first case series reporting off‐label use of combination TKI–IO for mRCC. TKI–IO combinations, particularly N+P and N+C, are well tolerated and efficacious. Although further prospective research is essential, slow disease progression on IO or TKI monotherapy may be safely controlled with addition of either TKI or IO. [ABSTRACT FROM AUTHOR]

Background: Pembrolizumab (Pembro) in combination with chemotherapy has been approved for the treatment of pretreated advanced NSCLC in the United States and China for its significant efficacy. However, the cost‐effectiveness is unknown considering Pembro's high price. The impact of programmed death ligand 1 (PD‐L1) test on the cost‐effectiveness is also unknown. The current study assessed the cost‐effectiveness of combination therapy for nonsquamous NSCLC from the United States and China public payers' perspective. Materials and Methods: A literature‐based Markov model was conducted using KEYNOTE‐189 trial data to compare cost and quality‐adjusted life years (QALYs) of three treatment strategies for nonsquamous NSCLC: Pembro‐chemotherapy combination and chemotherapy strategy without PD‐L1 test, and treatment strategy according to their PD‐L1 status. Results: In base case analysis, the combination strategy generated an additional 0.78 QALYs and 0.59 QALYs over chemotherapy in the United States and China respectively, resulting in an ICER of $132 392/QALY in the United States and $92 533/QALY in China. In the PD‐L1 ≥1% base case, the ICERs were $77 754/QALY and $56 768/QALY respectively in the United States and China for PD‐L1 test strategy. In the PD‐L1 ≥50% base case, the ICERs were $44 731/QALY and $34 388/QALY respectively in the United States and China for PD‐L1 test strategy. Lowering Pembro price can also partly decrease the ICERs. Conclusion: Compared with chemotherapy, the combination strategy is not cost‐effective for the treatment of NSCLC in the American and Chinese health care system at WTP threshold of $100 000/QALY for the United States and $27 351/QALY for China. Using PD‐L1 test for patient selection and price reduction could improve the cost‐effective probabilities of immunotherapy for nonsquamous NSCLC. [ABSTRACT FROM AUTHOR]

Background: Extranodal marginal zone B‐cell lymphoma of mucosa‐associated lymphoid tissue (MALT lymphoma) in the oromaxillofacial head and neck region is rare, with limited data available. This retrospective study explored the clinical features, stage, treatment, and prognosis of this disease. Methods: Overall, 105 patients with MALT lymphomas in the oromaxillofacial head and neck region were included in this retrospective analysis. SPSS 22.0 software package was used for data analysis and a two‐tailed P value of ≤.05 was considered statistically significant. Primary endpoints of the study were the complete response (CR) rate, overall survival (OS), and progression‐free survival (PFS). Results: About 52% of the patients had long‐term xerostomia, autoimmune diseases, or chronic parotitis and 81% had diseases involving the large salivary glands. Ann Arbor staging of the patients was as follows: stages I/II, 73 patients and stages III/IV, 32 patients. In the 97 patients followed up, CR rate after initial treatment was 80%. Tumor progression was observed in 12 patients and 14 patients died. There was a significant difference between the rate of CR in localized (87%) and disseminated (67%) lymphoma patients (P =.02). The 5‐ and 10‐year PFS of the localized lymphoma patients were both 91%, whereas those of the disseminated lymphoma patients were 83% and 65%, respectively (P =.03). The 5‐year PFS rates of the chemotherapy and non‐chemotherapy groups in the disseminated lymphoma patients were 85% and 73% (P =.04). Meanwhile, the 5‐year PFS rates of the rituximab and non‐rituximab groups in the disseminated lymphoma patients were 100% and 70% (P =.03). In multivariate analysis, MALT Lymphoma International Prognostic Index (MALT‐IPI) was an independent prognostic factor affecting OS, whereas Ann Arbor staging affected PFS. Conclusions: This study suggests that the outcome after initial treatment of MALT lymphomas in the oromaxillofacial head and neck region is satisfactory and that this disease progresses slowly. The CR rate and PFS of localized lymphoma patients are better than those of disseminated lymphoma patients. Systemic treatment (chemotherapy or rituximab) may improve PFS in disseminated disease patients. MALT‐IPI and Ann Arbor staging are independent prognostic factors. [ABSTRACT FROM AUTHOR]

Background: Pembrolizumab is approved for patients with metastatic, microsatellite instability (MSI)‐high or mismatch repair‐deficient (dMMR) solid tumors. However, very few men with prostate cancer were included in these initial studies. Methods: We performed a single institution retrospective review of men with metastatic castrate‐resistant prostate cancer (mCRPC) who were treated with pembrolizumab. The primary objective was to describe the clinical efficacy of pembrolizumab associated with patient and genomic characteristics. Results: We identified 48 men who received ≥1 cycle of pembrolizumab for mCRPC. Of these, 94% (45/48) had ≥3 prior lines of therapy for mCRPC. Somatic tumor sequencing was available in 18/48 men (38%). We found that 17% (8/48) had a ≥50% confirmed PSA decline with pembrolizumab, and 8% (4/48) had a ≥90% PSA decline with durations of response ranging from 3.1 to 16.3 months. Two of these four men had mutations in LRP1b, one of whom also had MSH2 loss and was MSI‐H and TMB‐high. Despite prior progression on enzalutamide, 48% (23/48) of men were treated with concurrent enzalutamide. The median PSA progression‐free‐survival was 1.8 months (range 0.4‐13.7 months), with 31% of patients remaining on pembrolizumab therapy and 54% of men remain alive with a median follow‐up of 7.1 months. Conclusions: In a heavily pretreated population of men with mCRPC, pembrolizumab was associated with a ≥50% PSA decline in 17% (8/48) of men, including a dramatic ≥90% PSA response in 8% (4/48), two of whom harbored pathogenic LRP1b mutations suggesting that LRP1b mutations may enrich for PD‐1 inhibitor responsiveness in prostate cancer. [ABSTRACT FROM AUTHOR]

Human colorectal cancer (CRC), characterized by its high morbidity and lethality, seriously threatens human health and lives. MicroRNA‐487b (miR‐487b) is currently reported to be aberrantly expressed in several tumors, but the detailed functions and underlying mechanisms of miR‐487b in CRC remain unclear. Here, we found that miR‐487b is downregulated in CRC cell lines and is markedly decreased in tumor specimens derived from CRC patients. MiR‐487b inhibits cell proliferation, migration and invasion and promotes the apoptosis of CRC cells in vitro. Statistical analysis of clinical samples indicates that miR‐487b may serve as a biomarker for early CRC diagnosis. Inverse correlations between the expression levels of MYC, SUZ12, and KRAS and that of miR‐487b exist in vitro and in CRC patient tissue specimens. Further experiments demonstrated the regulatory effects of miR‐487b on MYC, SUZ12, and KRAS, and the disruption of these genes partially restores the miR‐487b inhibitor‐induced phenotype. Additionally, miR‐487b promoter region is in a DNA hypermethylated condition and the DNA methyltransferase inhibitor 5‐aza‐2'‐deoxycytidine (5‐Aza) increases the levels of miR‐487b but suppresses the expression of MYC, SUZ12, and KRAS in a time‐ and concentration‐dependent manner in CRC cells. Collectively, miR‐487b is regulated by DNA methylation and it functions as a tumor suppressor in CRC mainly through targeting MYC, SUZ12, and KRAS. Our study provides insight into the regulatory network in CRC cells, offering a new target for treating CRC patients. [ABSTRACT FROM AUTHOR]

Abstract: Positive cofactor 4 (PC4) participates in DNA damage repair and involved in nonhomologous end joining (NHEJ). Our previous results demonstrated that knockdown of PC4 downregulated the expression of XRCC4‐like factor (XLF) in esophageal squamous cell carcinoma. However, the mechanism how PC4 regulates the expression of XLF remains unclear. Here, we found that knockdown of PC4 increased radiosensitivity of non‐small cell lung cancer (NSCLC) both in vivo and in vitro. Furthermore, we found that PC4 knockdown downregulated the expression of XLF, whereas recovering XLF expression restored radioresistance in the PC4‐knockdown NSCLC cells. In addition, PC4 knockdown inhibited XLF expression by transcriptionally suppressing of XLF. Moreover, PC4 expression correlated with radiosensitivity and was an independent prognostic factor of progression‐free survival (PFS) in patients with NSCLC. These findings suggest that PC4 could be used as a promising therapeutic target for NSCLC. [ABSTRACT FROM AUTHOR]