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Background: Regorafenib at different dosing strategies and TAS-102 are treatment options for refractory metastatic colorectal cancer (mCRC). We aimed to evaluate the comparative effectiveness evidence supporting these different strategies., Materials and Methods: We searched different databases for randomized controlled trials evaluating TAS-102 or regorafenib in patients with refractory mCRC who failed prior oxaliplatin, irinotecan, and fluoropyrimidine. Outcomes of interest included overall survival (OS) and progression-free survival (PFS). The overall effect was pooled using the DerSimonian random effects model. We conducted network meta-analysis based on White's multivariate meta-regression to pool evidence from direct and indirect comparisons., Results: Six trials at low risk of bias (2,445 patients) were included. Direct comparisons showed that Rego 160 and TAS-102 as monotherapy were superior to best-supportive care (BSC) in terms of PFS (Rego 160: hazard ratio [HR], 0.4; 95% confidence ratio [CI], 0.26-0.63; TAS-102: HR, 0.46 CI, 0.40-0.52) and OS (Rego 160: HR, 0.67; CI, 0.48-0.93; TAS-102: HR, 0.67; CI, 0.57-0.80). Network analysis showed no statistically difference in PFS or OS between Rego 160 and TAS-102. Rego 80+ was superior to BSC in terms of OS (HR, 0.44; CI, 0.23-0.84) and PFS (HR, 0.37; CI, 0.21-0.66). Rego 80+ was associated with statistically nonsignificant improvement in OS and PFS compared with TAS-102 and Rego 160., Conclusion: Regorafenib 160 and TAS-102 appear to have similar efficacy. Rego 80+ is shown to be superior to BSC. A trend for improved OS was observed with Rego 80+ versus Rego 160 or TAS 102., Implications for Practice: Regorafenib at a dose of 160 mg and TAS-102 appear to have similar efficacy in patients with refractory metastatic colorectal cancer. Regorafenib with a dose escalation strategy is superior to best-supportive care. Given its tolerability and the observed trend in survival benefit compared with regorafenib 160, dose escalation strategy of regorafenib (80+) may be the preferred option in this setting., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2019.) more...

Autologous stem cell transplantation (SCT) is the standard of care for all transplantation-eligible patients diagnosed with multiple myeloma (MM). Various studies have compared clinical outcomes with frontline SCT ("early SCT") versus standard-dose therapy (SDT) alone, with or without salvage SCT ("SDT/late SCT"). In this meta-analysis, we compare overall survival (OS) and progression-free survival (PFS) outcomes between these 2 treatment approaches. Twelve studies were identified, including a total of 3633 patients, of whom 1811 received early SCT and 1822 received SDT/late SCT. In our analysis of all 12 studies, OS was not significantly different between the 2 groups (hazard ratio [HR], .86; 95% confidence interval [CI], .70 to 1.04), but PFS was better with early SCT (HR, .67; 95% CI, .54 to .82). In a subgroup analysis of 3 studies in which novel agents were used for induction, OS again was similar in the 2 groups, and PFS was favorable with early SCT (HR, .50; 95% CI, .36 to .70). This analysis shows that over the years, early SCT has been associated with prolonged PFS, but this did not consequently translate into prolonged OS in patients with newly diagnosed MM. The benefit of early SCT in terms of OS is less clear in the era of novel agents, given the limited follow-up of these studies., (Copyright © 2018 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.) more...

Background: There are limited therapeutic options for treatment-refractory pancreatic ductal adenocarcinoma (PDAC), with a paucity of data to support the best option after progression on gemcitabine-based regimens. The authors performed a meta-analysis to determine the effectiveness of adding oxaliplatin (OX) or various irinotecan formulations to a fluoropyrimidine (FP) after first-line treatment progression in patients with PDAC., Methods: Different databases, including PubMed, EMBASE, and Cochrane, were searched to identify randomized controlled trials comparing FP monotherapy versus FP combination therapy that included either oxaliplatin (FPOX) or various irinotecan formulations (FPIRI) in patients with PDAC who progressed after first-line treatment. Secondary analyses were planned to assess the effectiveness of FPOX and FPIRI compared with FP. Outcomes of interest included overall survival (OS) and progression-free survival (PFS)., Results: Five studies with 895 patients were identified. Patients randomized to receive FPIRI/FPOX had a significantly improved PFS and a trend toward improved OS compared with those who received FP monotherapy. When comparing FPIRI with FP, there was an improvement in both PFS (hazard ratio, 0.64; 95% confidence interval, 0.47-0.87; P = .005) and OS (hazard ratio, 0.70; 95% confidence interval, 0.55-0.89; P = .004) in patients who received the combination. Conversely, FPOX produced only a modest improvement in PFS with no improvement in OS., Conclusions: Combination chemotherapy with OX or various IRI formulations appears to improve PFS compared with single-agent FP. FPIRI, but not FPOX, appears to confer an OS advantage. The combination of FP with irinotecan formulations appears to be the appropriate next line of treatment upon progression after gemcitabine-based chemotherapy regimens. Cancer 2017;123:4680-4686. © 2017 American Cancer Society., (© 2017 American Cancer Society.) more...