2020 ASCO, 2023 NCCN, 2023 MASCC/ESMO, and 2019 CCO: a comparison of antiemetic guidelines for the treatment of chemotherapy-induced nausea and vomiting in cancer patients.

Chemotherapy-induced nausea and vomiting (CINV) is a common toxicity that may impair the quality of life of patients with various malignancies ranging from early to end stages. In light of frequent changes to the guidelines for optimal management of CINV, we undertook this narrative review to compare the most recent guidelines published by ASCO (2020), NCCN (2023), MASCC/ESMO (2023), and CCO (2019). The processes undertaken by each organization to evaluate existing literature were also described. Although ASCO, NCCN, MASCC/ESMO, and CCO guidelines for the treatment and prevention of CINV share many fundamental similarities, the literature surrounding low and minimal emetic risk regimens is lacking. Current data regarding adherence to these guidelines is poor and warrants further investigation to improve care.

The CCTG PA.7 phase II trial of gemcitabine and nab-paclitaxel with or without durvalumab and tremelimumab as initial therapy in metastatic pancreatic ductal adenocarcinoma.

Immunotherapy-based monotherapy treatment in metastatic pancreatic ductal adenocarcinoma (mPDAC) has shown limited benefit outside of the mismatch repair deficiency setting, while safety and efficacy of combining dual-checkpoint inhibitor immunotherapy with chemotherapy remains uncertain. Here, we present results from the CCTG PA.7 study (NCT02879318), a randomized phase II trial comparing gemcitabine and nab-paclitaxel with and without immune checkpoint inhibitors durvalumab and tremelimumab in 180 patients with mPDAC. The primary endpoint was overall survival. Secondary endpoints included progression-free survival and objective response rate. Results of the trial were negative as combination immunotherapy did not improve survival among the unselected patient population (p = 0.72) and toxicity was limited to elevation of lymphocytes in the combination immunotherapy group (p = 0.02). Exploratory baseline circulating tumor DNA (ctDNA) sequencing revealed increased survival for patients with KRAS wildtype tumors in both the combination immunotherapy (p = 0.001) and chemotherapy (p = 0.004) groups. These data support the utility of ctDNA analysis in PDAC and the prognostic value of ctDNA-based KRAS mutation status.

Cancer treatment-related financial toxicity experienced by patients in low- and middle-income countries: a scoping review.

PURPOSE: In the past decade, literature has called attention to financial toxicities experienced by cancer patients. Though studies have addressed research questions in high-income countries, there remains a paucity of in-depth reviews regarding low- and middle-income countries (LMICs). Our scoping review provides an overview of treatment-related financial toxicities experienced by cancer patients in LMICs. METHODS: A systematic search was conducted in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. English peer-reviewed articles that (a) explored patients' experience with financial toxicity due to cancer treatment (b) were specific to LMICs as defined by the World Bank and (c) focused on qualitative data were included. Details regarding participants and main findings were extracted and synthesized. RESULTS: The search yielded 6290 citations, and 42 studies across 3 low-income, 9 lower-middle-income and 8 upper-middle-income countries. Main themes identified included cancer patients encountered various material hardships, managed costs with different coping behaviours and experienced negative psychological responses to their financial burden. Higher levels of financial toxicities were associated with patient characteristics such as lower socio-economic status and lack of insurance, as well as patient outcomes such as lower quality of life. CONCLUSION: Cancer patients in LMIC experience deleterious financial toxicities as a result of treatment. This comprehensive characterization of financial toxicities will better allow health systems to adopt evidence-based mitigation strategies to reduce the financial burden on patients.

Copy number and transcriptome alterations associated with metastatic lesion response to treatment in colorectal cancer.

BACKGROUND: Therapeutic resistance is the main cause of death in metastatic colorectal cancer. To investigate genomic plasticity, most specifically of metastatic lesions, associated with response to first-line systemic therapy, we collected longitudinal liver metastatic samples and characterized the copy number aberration (CNA) landscape and its effect on the transcriptome. METHODS: Liver metastatic biopsies were collected prior to treatment (pre, n = 97) and when clinical imaging demonstrated therapeutic resistance (post, n = 43). CNAs were inferred from whole exome sequencing and were correlated with both the status of the lesion and overall patient progression-free survival (PFS). We used RNA sequencing data from the same sample set to validate aberrations as well as independent datasets to prioritize candidate genes. RESULTS: We identified a significantly increased frequency gain of a unique CN, in liver metastatic lesions after first-line treatment, on chr18p11.32 harboring 10 genes, including TYMS, which has not been reported in primary tumors (GISTIC method and test of equal proportions, FDR-adjusted p = 0.0023). CNA lesion profiles exhibiting different treatment responses were compared and we detected focal genomic divergences in post-treatment resistant lesions but not in responder lesions (two-tailed Fisher's Exact test, unadjusted p ≤ 0.005). The importance of examining metastatic lesions is highlighted by the fact that 15 out of 18 independently validated CNA regions found to be associated with PFS in this study were only identified in the metastatic lesions and not in the primary tumors. CONCLUSION: This investigation of genomic-phenotype associations in a large colorectal cancer liver metastases cohort identified novel molecular features associated with treatment response, supporting the clinical importance of collecting metastatic samples in a defined clinical setting.

Safety and feasibility of initiating a hepatic artery infusion pump chemotherapy program for unresectable colorectal liver metastases: A multicenter, retrospective cohort study.

INTRODUCTION: Hepatic artery infusion pump (HAIP) chemotherapy is a specialized therapy for patients with unresectable colorectal liver metastases (uCRLM). Its effectiveness was demonstrated from a high volume center, with uncertainty regarding the feasibility and safety at other centers. Therefore, we sought to assess the safety and feasibility of HAIP for the management of uCRLM at other centers. METHODS: We conducted a multicenter retrospective cohort study of patients with uCRLM treated with HAIP from January 2003 to December 2017 at six North American centers initiating the HAIP program. Outcomes included the safety and feasibility of HAIP chemotherapy. RESULTS: We identified 154 patients with HAIP insertion and the median age of 54 (48-61) years. The burden of disease was >10 intra-hepatic metastatic foci in 59 (38.3%) patients. Patients received at least one cycle of systemic chemotherapy before HAIP insertion. Major complications occurred in 7 (4.6%) patients during their hospitalization and 13 (8.4%) patients developed biliary sclerosis during follow-up. A total of 148 patients (96.1%) received at least one-dose of HAIP chemotherapy with a median of 5 (4-7) cycles. 78 patients (56.5%) had a complete or partial response and 12 (7.8%) received a curative liver resection. CONCLUSION: HAIP programs can be safely and effectively initiated in previously inexperienced centers with good response.

Effect of sorafenib starting dose and dose intensity on survival in patients with hepatocellular carcinoma: Results from a Canadian Multicenter Database.

BACKGROUND: Sorafenib has been shown to improve survival in patients with advanced hepatocellular carcinoma (HCC), however, full dose can be difficult to tolerate. The aim of this study was to determine whether sorafenib starting dose and mean dose intensity affect survival. METHODS: Patients treated with sorafenib for HCC from January 2008 to July 2016 in several Canadian provinces were included and retrospectively analyzed. The primary end point was overall survival (OS) of patients starting on sorafenib full dose compared to reduced dose. Secondary analysis compared OS with different mean dose-intensity groups. Survival outcomes were assessed with Kaplan-Meier curves and Cox proportional hazards models. A propensity score analysis was performed to account for treatment bias and confounding. RESULTS: Of 681 patients included, sorafenib was started at full dose in 289 patients (42%). Median survival for starting full and reduced dose was 9.4 months and 8.9 months (P = .15) respectively. After propensity score matching and adjusting for potential confounders there was still no difference in survival (HR 0.8, 95% CI, 0.61-1.06, P = .12). Almost half of the patients (45%) received a dose intensity < 50%. Median survival for mean dose intensity > 75%, 50%-75%, and < 50% were 9.5 months, 12.9 months, and 7.1 months (P = .005) respectively. In multivariable models, starting dose(HR 1.16, 95% CI 0.93-1.44, P = .180) and mean dose intensity were not associated with survival. CONCLUSIONS: Starting HCC patients on a reduced dose of sorafenib compared to full dose may not compromise survival. Mean dose-intensity of sorafenib may also not affect survival.

Second-line treatment of hepatocellular carcinoma after sorafenib: Characterizing treatments used over the past 10 years and real-world eligibility for cabozantinib, regorafenib, and ramucirumab.

BACKGROUND: The CELESTIAL, RESORCE, and REACH-2 trials showed survival benefit of cabozantinib, regorafenib, and ramucirumab, respectively, in hepatocellular carcinoma (HCC) patients treated with sorafenib who had good performance status (ECOG 0-1) and liver function (Child-Pugh-A). This study characterizes subsequent treatments received by HCC patients after sorafenib, and determines the proportion of patients eligible for novel therapies if strict eligibility criteria (SEC) were utilized compared to more liberal modified eligibility criteria (MEC, including ECOG 2, Child-Pugh-B7). METHODS: HCC patients who received sorafenib between 2008 and 2017 were included from the Canadian HCC CHORD Database. Patients were classified as eligible or ineligible based on available CELESTIAL, RESORCE, and REACH-2 trial SEC or MEC. Median overall survival (mOS) was assessed using the Kaplan-Meier method. RESULTS: A total of 730 patients were identified; and 172 (23.6%) received subsequent treatment. Patients who received subsequent treatment had longer mOS than those who did not (12.1 vs 3.3 months; P < .001). Using SEC, only 13.1% of patients would be eligible for cabozantinib, regorafenib, or ramucirumab. Expanding eligibility to include patients who meet MEC increased the proportion of eligible patients to 31.7%. Higher ineligibility for regorafenib and ramucirumab was driven by trial-specific criteria, including sorafenib intolerance (28%) for RESORCE and AFP <400 (58.9%) for REACH-2. CONCLUSIONS: A small proportion of real-world HCC patients would be eligible for cabozantinib, regorafenib, or ramucirumab if SEC in clinical trials were followed, while more than double would be eligible if MEC were applied. Patients who received subsequent treatment had improved mOS, regardless of whether they met SEC or MEC.

Adjuvant treatment for resected pancreatic adenocarcinoma: A systematic review and network meta-analysis.

Adjuvant chemotherapy has significantly improved outcomes following surgical resection for pancreatic adenocarcinoma; however, the optimal adjuvant strategy remains unclear. This systematic review and network meta-analysis was conducted to provide indirect comparative evidence across adjuvant chemotherapies. Electronic searches of EMBASE, MEDLINE, Cochrane and ASCO databases were conducted to identify eligible randomized controlled trials (RCT). Direct pairwise meta-analysis was conducted for disease-free survival (DFS), overall-survival (OS) and adverse events (AE). Network meta-analysis of DFS and OS was conducted to evaluate indirect comparisons. Ten publications of eleven RCT met eligibility criteria. Indirect DFS comparison demonstrated superiority of mFOLFIRINOX versus gemcitabine-capecitabine, gemcitabine-erlotinib and gemcitabine-nab-paclitaxel. S-1 demonstrated a DFS benefit versus gemcitabine-capecitabine, gemcitabine-erlotinib, gemcitabine-nab-paclitaxel. OS benefits were demonstrated for mFOLFIRINOX verus gemcitabine-erlotinib and for S-1 versus gemcitabine-based combination with erlotinib, capecitabine and nab-paclitaxel. In conclusion, mFOLFIRINOX is the preferred approach for adjuvant therapy. For mFOLFIRINOX-ineligible patients no additional benefit is seen with gemcitabine-nab-paclitaxel.

Outcomes of extra-cranial stereotactic body radiotherapy for metastatic colorectal cancer: Dose and site of metastases matter.

BACKGROUND AND PURPOSE: To review the clinical outcomes following the use of stereotactic body radiotherapy (SBRT) in patients with metastatic colorectal cancer (mCRC) from a large academic institution. MATERIALS AND METHODS: Patients with mCRC treated with extracranial SBRT between 2008 and 2016 were identified from an institutional database. Treatment indications were oligometastases, oligoprogression, and local control of dominant tumors. Endpoints included local progression (LP), overall survival (OS), progression-free survival (PFS), and cumulative incidence of starting or changing systemic therapy (SCST). Univariate and multivariable analyses (MVA) were performed to identify predictive factors. RESULTS: One hundred and sixty-five patients (262 lesions treated) were included. The 2-year cumulative incidence of LP was 23.8%. Lower SBRT doses and tumor location in the liver were significant predictors of LP on MVA. Median OS was 49.3 months, 19.3 months, and 9.0 months for oligometastases, oligoprogression, and local control of dominant tumors, respectively. Primary tumor not in situ, smaller tumors, fewer lines of previous systemic therapy, lower CEA, and oligometastases treatment indications were significant predictors of higher OS on MVA. For the entire cohort, median PFS was 9.9 months, while oligometastatic patients had a median PFS of 12.4 months. 2-year cumulative incidence of SCST was 41.7%. CONCLUSIONS: Survival outcomes are favorable after SBRT for mCRC patients. A significant proportion of patients did not have a change in systemic therapy after SBRT. Higher doses are required to obtain the best local control. Efforts should be made to better optimize SBRT delivery for liver metastases given their higher local failure rate.

Aflibercept Plus FOLFIRI for Second-line Treatment of Metastatic Colorectal Cancer: Observations from the Global Aflibercept Safety and Health-Related Quality-of-Life Program (ASQoP).

BACKGROUND: The objectives of this study were to evaluate the safety profile of aflibercept and health-related quality of life (HRQL) in patients with metastatic colorectal cancer (mCRC) provided with aflibercept access before marketing authorization. PATIENTS AND METHODS: Patients received aflibercept followed by FOLFIRI (fluorouracil, leucovorin, irinotecan) on day 1 of a 2-week cycle until disease progression, unacceptable toxicity, death, or patient/investigator decision to discontinue. Treatment-emergent adverse events (TEAEs) were evaluated, and HRQL was assessed at baseline, cycle 3, and every other cycle using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-CR29, and EuroQol 5-Dimensions 3-Levels questionnaires (NCT01571284). RESULTS: Overall, 779 adult patients with mCRC, who received ≥ 1 prior oxaliplatin-based regimen and had disease progression during or following their last administration of oxaliplatin-based chemotherapy, were enrolled. At data cutoff, all patients had discontinued treatment, mainly owing to disease progression (51.7%). The most common TEAEs of any grade were diarrhea (61.6%), hypertension (48.4%), and nausea (43.3%). The most common grade 3/4 TEAEs were hypertension (24.1%), neutropenia (23.1%), and diarrhea (15.3%). Clinically meaningful changes in HRQL were reported for all measures. Most patients either had an improvement in their HRQL scores or remained stable during the treatment period based on patient-reported outcomes. CONCLUSION: The data from this study support the tolerability of the combination of aflibercept and FOLFIRI in a setting that more closely approximates real life in patients with mCRC who failed to respond to oxaliplatin-based chemotherapy, and also suggest an improvement in HRQL.

Prognosis of patients with hepatocellular carcinoma treated with sorafenib: a comparison of five models in a large Canadian database.

Several systems (tumor-node-metastasis [TNM], Barcelona Clinic Liver Cancer [BCLC], Okuda, Cancer of the Liver Italian Program [CLIP], and albumin-bilirubin grade [ALBI]) were developed to estimate the prognosis of patients with hepatocellular carcinoma (HCC) mostly prior to the prevalent use of sorafenib. We aimed to compare the prognostic and discriminatory power of these models in predicting survival for HCC patients treated with sorafenib and to identify independent prognostic factors for survival in this population. Patients who received sorafenib for the treatment of HCC between 1 January 2008 and 30 June 2015 in the provinces of British Columbia and Alberta, and two large cancer centers in Toronto, Ontario, were included. Survival was assessed using the Kaplan-Meier method. Multivariate Cox regression was used to identify predictors of survival. The models were compared with respect to homogeneity, discriminatory ability, monotonicity of gradients, time-dependent area under the curve, and Akaike information criterion. A total of 681 patients were included. 80% were males, 86% had Child-Pugh class A, and 37% of patients were East Asians. The most common etiology for liver disease was hepatitis B (34%) and C (31%). In all model comparisons, CLIP performed better while BCLC and TNM7 performed less favorably but the differences were small. The utility of each system in allocating patients into different prognostic groups varied, for example, TNM poorly differentiated patients in advanced stages (8.7 months (m) (95% CI 6.5-11.5) versus 8.4 m (95% CI 7.0-9.6) for stages III and IV, respectively) while ALBI had excellent discrimination of early grades (15.6 m [95% CI 13.0-18.4] versus 8.3 m [95% CI 7.0-9.2] for grades 1 and 2, respectively). On multivariate analysis, hepatitis C, alcoholism, and prior hepatic resection were independently prognostic of better survival (P < 0.01). In conclusion, none of the prognostic systems was optimal in predicting survival in sorafenib-treated patients with HCC. Etiology of liver disease should be considered in future models and clinical trial designs.

A Randomized Phase II Study of FOLFOX6/Bevacizumab With or Without Pelareorep in Patients With Metastatic Colorectal Cancer: IND.210, a Canadian Cancer Trials Group Trial.

BACKGROUND: Oncolytic reovirus pelareorep might preferentially infect and destroy rat sarcoma (RAS)-activated cells, and has preclinical and early clinical activity against colorectal cancer (CRC). PATIENTS AND METHODS: After a 6-patient safety run-in, 103 patients with metastatic CRC were randomly assigned to standard first-line leucovorin/5-FU/oxaliplatin (FOLFOX6)/bevacizumab (FOLFOX/BEV) every 2 weeks with (n = 51) or without (n = 52) pelareorep 3 × 1010 tissue culture infective dose 50 on days 1 to 5 (cycles 1, 2, 4, and alternate cycles thereafter). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), quality of life, and correlative analyses. RESULTS: At 13 months' median follow-up, PFS was inferior in the pelareorep arm (median 7 vs. 9 months; hazard ratio [HR], 1.59 [80% confidence interval (CI), 1.18-2.15]; P = .046). There was no statistical difference in OS (median, 19.2 vs. 20.1 months; HR, 1.22; P = .38). An increased ORR was observed with pelareorep (adjusted odds ratio, 2.52 [80% CI, 1.44-4.41]; P = .03), but with a shorter median duration of response (5 vs. 9 months; P = .028). Pelareorep patients experienced more hypertension and proteinuria, and were more likely to omit bevacizumab before progression. A trend to lower dose intensity and shorter oxaliplatin and bevacizumab treatment duration was observed with pelareorep. CONCLUSION: Combination pelareorep with FOLFOX/BEV was tolerable with an increased ORR, but PFS was inferior. Subgroup analysis of baseline variables including Kirsten rat sarcoma oncogene did not identify subgroups with PFS benefit. Decreased treatment intensity with standard agents likely contributed to the lack of benefit with pelareorep. Future studies might consider alternate pelareorep/chemotherapy strategies or combination therapy with novel agents.

Perfusion imaging of colorectal liver metastases treated with bevacizumab and stereotactic body radiotherapy.

Stereotactic body radiotherapy (SBRT) and bevacizumab are used in the treatment of colorectal liver metastases. This study prospectively evaluated changes in perfusion of liver metastases in seven patients treated with both bevacizumab and SBRT. Functional imaging using dynamic contrast-enhanced CT perfusion and contrast-enhanced ultrasound were performed at baseline, after bevacizumab, and after SBRT. After bevacizumab, a significant decrease was found in permeability (-28%, p < .05) and blood volume (-47%, p < .05), while SBRT led to a significant reduction in permeability (-22%, p < .05) and blood flow (-37%, p < .05). This study demonstrates that changes in perfusion can be detected after bevacizumab and SBRT.

A Comparison of Regorafenib and TAS-102 for Metastatic Colorectal Cancer: A Systematic Review and Network Meta-analysis.

BACKGROUND: Regorafenib and TAS-102 have shown to be superior to placebo in refractory metastatic colorectal cancer. However, no studies have directly compared both drugs. Giving the lack of standard options in this scenario, a systematic review to compare the efficacy and safety of regorafenib and TAS-102 was performed. MATERIALS AND METHODS: A systematic review using the PubMed, Medline, Embase, Scopus, and Cochrane databases to identify published and unpublished studies up to November 2015 for randomized controlled trials for patients with metastatic colorectal cancer, involving regorafenib or TAS-102, was performed. Data including overall survival, progression-free survival, and toxicity were extracted. Pairwise direct meta-analyses (regorafenib vs. placebo and TAS-102 vs. placebo) and indirect comparison (regorafenib vs. TAS-102) using network meta-analyses methods to preserve randomization were performed using random effects. RESULTS: Three randomized controlled trials fulfilled eligibility criteria (regorafenib monotherapy for previously treated metastatic colorectal cancer [CORRECT]: an international, multicentre, randomised, pacebo-controlled, phase 3 trial, regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer [CONCUR]: a randomised, double-blind, placebo-controlled, phase 3 trial, and randomized trial of TAS-102 for refractory metastatic colorectal cancer [RECOURSE] trials) involving 1764 patients (regorafenib, 641; TAS-102, 534; placebo, 589). Subgroups of patients (1659) who had not received prior regorafenib or TAS-102 were used to perform meta-analyses for efficacy. In the indirect comparison, no statistically significant differences were observed between regorafenib and TAS-102 in overall survival (hazard ratio, 0.96; 95% confidence interval [CI], 0.57-1.66; P = .91) or progression-free survival (hazard ratio, 0.85; 95% CI, 0.40-1.81; P = .67). However, regorafenib has statistically more all grade any toxicity (risk difference, 0.31; 95% CI, 0.25-0.38; P = .001) compared with TAS-102. Subgroup analysis of adverse events showed a different toxicity profile between both drugs. CONCLUSION: In this indirect comparison, regorafenib and TAS-102 appeared to have similar efficacy. However, regorafenib was associated with more toxicity compared with TAS-102.

Cost-Effectiveness Analysis of Systemic Therapies in Advanced Pancreatic Cancer in the Canadian Health Care System.

OBJECTIVES: To assess the cost-effectiveness of gemcitabine (G), G + 5-fluorouracil, G + capecitabine, G + cisplatin, G + oxaliplatin, G + erlotinib, G + nab-paclitaxel (GnP), and FOLFIRINOX in the treatment of advanced pancreatic cancer from a Canadian public health payer's perspective, using data from a recently published Bayesian network meta-analysis. METHODS: Analysis was conducted through a three-state Markov model and used data on the progression of disease with treatment from the gemcitabine arms of randomized controlled trials combined with estimates from the network meta-analysis for the newer regimens. Estimates of health care costs were obtained from local providers, and utilities were derived from the literature. The model estimates the effect of treatment regimens on costs and quality-adjusted life-years (QALYs) discounted at 5% per annum. RESULTS: At a willingness-to-pay (WTP) threshold of greater than $30,666 per QALY, FOLFIRINOX would be the most optimal regimen. For a WTP threshold of $50,000 per QALY, the probability that FOLFIRINOX would be optimal was 57.8%. There was no price reduction for nab-paclitaxel when GnP was optimal. CONCLUSIONS: From a Canadian public health payer's perspective at the present time and drug prices, FOLFIRINOX is the optimal regimen on the basis of the cost-effectiveness criterion. GnP is not cost-effective regardless of the WTP threshold.

Cetuximab plus irinotecan versus panitumumab in patients with refractory metastatic colorectal cancer in Ontario, Canada.

The addition of irinotecan to an epidermal growth factor receptor (EGFR) antibody has previously been shown to improve tumor response rate and time to progression but not overall survival (OS) for refractory metastatic colorectal cancer (mCRC). We assessed the "real-world" effectiveness and toxicity of the combination versus monotherapy. In Ontario, Canada, universal public funding is available for either cetuximab plus irinotecan (Cmab + I) combination therapy or panitumumab (Pmab) monotherapy, only in patients with refractory nonmutated RAS mCRC. All patients diagnosed before December 2012 and treated with an EGFR antibody for mCRC were identified from the Ontario drug database and linked to the Ontario Cancer Registry and other administrative databases to ascertain baseline characteristics, health services utilization, and outcomes. Multivariable Cox and logistic models were constructed to compare the time to treatment discontinuation (TTD), OS, emergency department (ED) or hospital visits between Cmab + I and Pmab. Observable confounders were adjusted for using propensity score methods. One thousand and eighty-one patients were identified (Cmab + I: 278, Pmab: 803). Patients receiving Cmab + I were younger (mean age 61 vs 64 years) and had a longer duration of prior irinotecan treatment. The use of Cmab + I as compared to Pmab alone was associated with a prolonged TTD [median: 3.8 months vs 2.8 months] and an improved OS [median: 8.8 months vs. 5.9 months] with an adjusted HR of 0.62 [95% CI 0.53-0.73, p < 0.001]. Both treatment regimens afforded similar 14-day mortality and incidence of ED or hospital visits. The findings for patients over and below the age of 65 were similar.

A Bayesian network meta-analysis on second-line systemic therapy in advanced gastric cancer.

BACKGROUND: It is unclear which regimen is the most efficacious among the available therapies for advanced gastric cancer in the second-line setting. We performed a network meta-analysis to determine their relative benefits. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) through the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases and American Society of Clinical Oncology abstracts up to June 2014 to identify phase III RCTs on advanced gastric cancer in the second-line setting. Overall survival (OS) data were the primary outcome of interest. Hazard ratios (HRs) were extracted from the publications on the basis of reported values or were extracted from survival curves by established methods. A Bayesian network meta-analysis was performed with WinBUGS to compare all regimens simultaneously. RESULTS: Eight RCTs (2439 patients) were identified and contained extractable data for quantitative analysis. Network meta-analysis showed that paclitaxel plus ramucirumab was superior to single-agent ramucirumab [OS HR 0.51, 95 % credible region (CR) 0.30-0.86], paclitaxel (OS HR 0.81, 95 % CR 0.68-0.96), docetaxel (OS HR 0.56, 95 % CR 0.33-0.94), and irinotecan (OS HR 0.71, 95 % CR 0.52-0.99). Paclitaxel plus ramucirumab also had an 89 % probability of being the best regimen among all these regimens. Single-agent ramucirumab, paclitaxel, docetaxel, and irinotecan were comparable to each other with respect to OS and were superior to best supportive care. CONCLUSIONS: This is the first network meta-analysis to compare all second-line regimens reported in phase III gastric cancer trials. The results suggest the paclitaxel plus ramucirumab combination is the most effective therapy and should be the reference regimen for future comparative trials.

PANCREOX: A Randomized Phase III Study of Fluorouracil/Leucovorin With or Without Oxaliplatin for Second-Line Advanced Pancreatic Cancer in Patients Who Have Received Gemcitabine-Based Chemotherapy.

Purpose The standard of care for second-line therapy in patients with advanced pancreatic cancer after gemcitabine-based therapy is not clearly defined. The CONKO-003 phase III study reported a survival benefit with second-line fluorouracil (FU) and oxaliplatin using the oxaliplatin, folinic acid, and FU (OFF) regimen. 1 PANCREOX was a phase III multicenter trial to evaluate the benefit of FU and oxaliplatin administered as modified FOLFOX6 (mFOLFOX6; infusional fluorouracil, leucovorin, and oxaliplatin) versus infusional FU/leucovorin (LV) in this setting. Patients and Methods Patients with confirmed advanced pancreatic cancer who were previously treated with gemcitabine therapy and with an Eastern Cooperative Oncology Group performance status of 0-2 were eligible. A total of 108 patients were randomly assigned to receive biweekly mFOLFOX6 or infusional FU/LV until progression. Progression-free survival (PFS) was the primary end point. Results Baseline patient characteristics were similar in both arms. No difference was observed in PFS (median, 3.1 months v 2.9 months; P = .99). Overall survival (OS) was inferior in patients assigned to mFOLFOX6 (median, 6.1 months v 9.9 months; P = .02). Increased toxicity was observed with the addition of oxaliplatin, with grade 3/4 adverse events occurring in 63% of patients who received mFOLFOX6 and 11% of those who received FU/LV. More patients in the mFOLFOX6 arm withdrew from study due to adverse events than in the FU/LV arm (20% v 2%), whereas the use of postprogression therapy was significantly higher in the FU/LV arm (25% v 7%; P = .015). No significant differences were observed in time to deterioration on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 global health scale. Conclusion No benefit was observed with the addition of oxaliplatin, administered as mFOLFOX6, versus infusional FU/LV in patients with advanced pancreatic cancer previously treated with first-line gemcitabine.

The impact of additional malignancies in patients diagnosed with gastrointestinal stromal tumors.

A higher incidence of additional malignancies has been described in patients diagnosed with gastrointestinal stromal tumors (GIST). This study aimed to identify risk factors for developing additional malignancies in patients diagnosed with GIST and evaluate the impact on survival. Individuals diagnosed with GIST from 2001 to2009 were identified from the SEER database. Logistic regression was used to identify predictors of additional malignancies and Cox-proportional hazards regression used to identify predictors of survival. In the study period, 1705 cases of GIST were identified, with 181 (10.6%) patients developing additional malignancies. Colorectal cancer was the most common cancer developing within 6 months of GIST diagnosis (30%). The median time to diagnosis of a malignancy after 6 months of GIST diagnosis was 21.9 months. Older age (p < 0.0001) and extraoesophagogastric GIST (p = 0.0027) were significant prognostic factors associated with additional malignancies. The overall 5-year survival was 65%, with the presence of additional malignancies within 6 months of GIST diagnosis associated with poor overall survival (54%, HR 1.55 1.05-2.3 95% CI, p = 0.04). Predictive factors of additional malignancies in patients diagnosed with GIST are increasing age and the primary disease site. Developing additional malignancies within 6 months of GIST diagnosis is associated with poorer overall survival. Targeted surveillance may be warranted in patients diagnosed with GIST that are at high risk of developing additional malignancies.