Common Chemotherapy Regimens Research Articles

The Demographic, Clinical and Survival Rate of Classical Hogkings Lymphoma Patients in Oman, Retrospective Study

Background and ObjectivesHodgkin's lymphoma (HL) is a B cell lymphoma characterized by the presence of Reed-Sternberg cells. HL comprises 1% of all cancer cases and 14% of all lymphoma cases. The clinical presentation and survival rate of these patients have not been described in Oman. We, therefore, aimed to describe the clinical characteristics and survival rate of patients with classical Hodgkin's lymphoma.MethodsThis is a retrospective study that was conducted in a tertiary care centers in the Sultanate of Oman. All Omani adults with histopathological confirmed diagnosis of classical Hodgkin's lymphoma from 2000 to 2016 were included in this study. The demographic, clinical, and survival rate were recorded and analyzed.ResultsA total of 273 patients (45 % females and 55% males, mean age 32) fulfilled the inclusion criteria with histopathological confirmed diagnosis of classical Hodgkin's lymphoma. The commonest presenting feature was lymph node enlargement (83%); followed by fever (48%). The most common classical HL histological subtype was nodular sclerosing HL (NSHL) (71%). The most common stage was II 34%. The most common chemotherapy regimen used as the first line was doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) (89%). Five and 10-year survival rates were 93.8 % and 99.2%, respectively.ConclusionsThis is the first study that demonstrates the demographic, clinical and survival rate of HL patients in Oman, and provides a general picture of the HL patients in our country. DisclosuresNo relevant conflicts of interest to declare.

Hematopoietic Stem Cell Transplant in Novel Agent Era Is Associated with Improved Survival in Relapsed and Refractory Peripheral T-Cell Lymphoma

BackgroundConventional salvage chemotherapy has limited efficacy in relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL). In the last decade, several novel agents, including pralatrexate, an antifolate, brentuximab vedotin (BV), a CD30-directed antibody-drug conjugate, and romidepsin, a histone deacetylase inhibitor, have been introduced into clinical practice based on phase 2 data demonstrating efficacy in relapsed/refractory (R/R) diseases. Their impact on real world survival remains to be defined. In this single-center retrospective cohort study we assessed survival including outcomes after hematopoietic stem cell transplant (HSCT) with respect to novel agent exposure.MethodsPatients diagnosed with PTCL from 2012-2017 who consented for inclusion in the Weill Cornell lymphoma and bone marrow transplant databases with adequate treatment records were included. Medical records were reviewed for baseline characteristics, treatment course, and outcomes including overall survival and HSCT. Median follow-up time was estimated on overall survival by reverse Kaplan-Meier method. Overall Survival (OS) time was calculated from date of diagnosis to date of death or last follow-up. Kaplan-Meier estimator was used to estimate survival probability. Survival difference between groups was tested by log-rank test and Cox regression analysis for statistical significance.ResultsA total of 123 cases were reviewed with median follow-up of 34 months. The major PTCL subtypes were PTCL NOS (N=34, 27.6%), angioimmunoblastic T-cell lymphoma (N=21, 17%), adult T-cell leukemia/lymphoma (N=19, 15.4%), and anaplastic large cell lymphoma (N=14, 11.4%). The most common 1st line chemotherapy regimens were CHOP (N=34, 31.5%), EPOCH (N=21, 19.4%), or CHOEP (N=10, 9.3%). Ninety-two patients had relapsed or refractory disease, and the most common 2nd line therapies were DICE/ICE (N=17, 18.4%), gemcitabine-based regimens (N=6, 7.5%), bendamustine (N=5, 5.4%), hyperCVAD (N=5, 5.4%), or combinations of novel agents. Thirty-three R/R patients received a novel agent, including pralatrexate alone (N=3), BV (N=13), or romidepsin (N=17). Thirty-six R/R patients underwent HSCT, including 26 allogeneic and 10 autologous.Baseline characteristics at diagnosis including age, gender, Ann Arbor stage, ECOG status, and IPI were similar between R/R patients who received a novel agent and those who did not. Although no differences in OS were seen with novel agent use among patients with R/R disease, there was a significant difference in OS among patients who received HSCT and those who did not (p=0.012 by log-rank test). Compared to no HSCT, significantly improved survival was observed in patients receiving allogeneic HSCT (HR = 0.47, p = 0.03) as well as autologous HSCT (HR = 0.27, p= 0.03) by Cox regression survival analysis, both univariate and multivariate when adjusting for interaction with novel agents.ConclusionData from this single-center retrospective cohort study suggest that hematopoietic stem cell transplant, both autologous and allogeneic, was associated with overall survival benefit in R/R diseases in the novel agent era. The real world impact of novel agents use in PTCL subtypes warrants further study, preferably in a prospectively designed multicenter population study with larger sample size where disease subtypes, therapeutic targets of novel agents, and line of therapies can be sufficiently delineated for response and survival analysis. DisclosuresMartin:AstraZeneca: Consultancy; Gilead: Consultancy; Bayer: Consultancy; Janssen: Consultancy; Seattle Genetics: Consultancy; Kite: Consultancy. Allan:Acerta: Consultancy; Sunesis: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees. Furman:TG Therapeutics: Consultancy; Sunesis: Consultancy; Loxo Oncology: Consultancy; Incyte: Consultancy, Other: DSMB; Gilead: Consultancy; Genentech: Consultancy; Acerta: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy; Verastem: Consultancy; Janssen: Consultancy; AbbVie: Consultancy.

P3.01-51 Outcomes with Systemic Chemotherapy in Advanced NSCLC Patients with Performance Status 2 and Above and without Driver Mutation

Platinum-based combination chemotherapy is recommended as the standard treatment for patients with advanced NSCLC, but its benefit is limited to patients with performance status (PS) of 0 or 1. However, it is not clear whether these benefits apply to patients with poor performance status ((PS 2 and above)). These patients have inferior outcomes and have been excluded from clinical trials. This population accounts for a significant portion (up to 30%) of patients of our practice and some of them have been treated with systemic chemotherapy based on clinician’s discretion. We have analyzed the outcome of these patients who have been treated with chemotherapy despite poor performance status. We performed a retrospective analysis of patients of advanced NSCLC with poor PS (ECOG PS 2 or more) registered at our lung cancer clinic between January 2016 and September 2017 and treated with systemic chemotherapy. Patients with driver mutations who were treated with first line TKIs were excluded. Hospital case records were reviewed for baseline characteristics, treatment details and outcome data. A total of 78 patients were found to be eligible for this analysis. Median age was 60 years (33-77 years) including 15% patients 70 years or above. At presentation out of these 78 patients, 48 (62.5%) were smokers, 24 patients (30%) had pleural effusion, 8 patients (10%) had brain metastasis and 30 patients (38%) had bone metastasis. Majority patients had ECOG PS 2 but 35 % had PS 3 or 4 also and 38(48%) had one or more associated comorbidities. The most common chemotherapy regimen used was weekly paclitaxel and carboplatin (50%) followed by pemetrexed and carboplatin (23%). Majority (61.5%) patients could complete 4 or more cycles of chemotherapy however 10 patients (13%) could receive only one cycle and 21 (27%) patients even received maintenance chemotherapy. Chemotherapy was interrupted or stopped due to toxicity in 33% patients. At least one point improvement in ECOG PS from baseline was observed in 44 patients (56%) after 2 cycles of chemotherapy. Objective response and disease control rates were 21 % and 48.6 % respectively. After a median follows up of 8.6 months, median progression free survival was 5.8 months. Systemic chemotherapy in modified doses and schedules in advanced NSCLC patients with PS 2 and above is feasible and may be associated with better symptom palliation with clinical benefit and improvement in survival. Further studies addressing this neglected subgroup are indicated.

Febrile neutropenia (FN) occurrence outside of clinical trials: occurrence and predictive factors in adult patients treated with chemotherapy and an expected moderate FN risk. Rationale and design of a real-world prospective, observational, multinational study

BackgroundFebrile neutropenia (FN) is a common occurrence during chemotherapy. Granulocyte colony-stimulating factors (G-CSFs) can significantly reduce the risk of FN. International guidelines recommend G-CSF for patients receiving chemotherapy with FN risk of ≥20% or 10% to 20% with defined risk factors. Prophylaxis is not typically recommended for FN risk of < 10%; however, few studies have investigated FN incidence in lower-risk patients in real-world settings and tried to identify higher-risk subgroups.MethodsThis real-world prospective, observational, multinational study aims to estimate the rate of development of FN with a chemotherapy line expected to be associated with a 10% to 20% risk of FN. Eligible patients (> 18 years of age) will have a solid tumour or Hodgkin/non-Hodgkin lymphoma and a planned chemotherapy regimen with expected risk of FN of 10% to 20% (according to published guidelines). Patients will be observed for the duration of the chemotherapy line (first cycle administered without FN prophylaxis). Primary endpoint is incidence of FN after the first chemotherapy cycle. Secondary outcomes include: FN-associated morbidity and mortality; time to first FN occurrence; other FN risk factors and impact of FN on quality of life. A risk model using occurrence of FN as a binary outcome will be developed. Data will be stratified by age, comorbidities and other risk factors.DiscussionThis study will provide insight into the real FN risk for common chemotherapy regimens and predictive factors for FN, including patients generally excluded from randomised clinical trials, from which reported FN rates have been variable. This study builds on knowledge of predictive factors from other research and will provide information on patients with 10% to 20% FN risk.

Efficacy of common salvage chemotherapy regimens in patients with refractory or relapsed acute myeloid leukemia: A retrospective cohort study.

To assess treatment response and overall survival (OS) in refractory or relapsed acute myeloid leukemia (R/R AML) patients treated by different common salvage chemotherapy regimens.Medical records data from 142 R/R AML patients were reviewed in this retrospective study. Patients were treated with regimens based on the following drugs: cytarabine, granulocyte colony-stimulating factor (G-CSF), and fludarabine (FLAG) (n = 46); cytarabine and G-CSF in addition to aclarubicin or daunorubicin (CAG/DAG) (n = 30); cytarabine, G-CSF, and cladribine (CLAG) (n = 27); cytarabine, etoposide, and mitoxantrone (MEA) (n = 17); cytarabine plus idarubicin, daunorubicin, or mitoxantrone (IA/DA/MA) (n = 12); and homoharringtonine, cytarabine, and aclarubicin or daunorubicin (HAA/HAD) (n = 10).A total of 43 (35.2%) patients achieved complete remission (CR), 60 (49.2%) patients achieved overall remission rate (ORR), and 18 (14.8%) patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CR. Median OS was 8.0 (95% CI 6.6-9.4) months with a 1-year OS rate of (29.9 ± 3.9)% and 3-year OS rate of (11.1 ± 3.6)%. No difference of CR (P = .621), ORR (P = .385), and allo-HSCT (P = .537) achievement was observed among different chemotherapy regimens. Interestingly, we observed that the CLAG-based regimen did not affect CR (P = .165), while it achieved a numerically higher ORR (P = .093) and was an independent factor for prolonged OS (P = .016). No other regimens were determined to be correlated with CR, ORR, or OS.FLAG-, CAG/DAG-, CLAG-, MEA-, IA/DA/MA- and HAA/HAD-based regimens were found to achieve similar CR rates, while the CLAG-based regimen achieved numerically higher ORR rates and significant favorable OS. Therefore, CLAG-based regimens should be a prioritized treatment option for R/R AML patients.

Transitioning historically inpatient chemotherapy regimens for hematologic malignancies to the ambulatory care setting.

With an increasing focus on patient-centric delivery of care and growing financial constraints on healthcare, several common oncology chemotherapy regimens traditionally administered in the inpatient setting have been considered and evaluated in the ambulatory care setting. Although most solid

Metastatic Gastric cancer: Real world scenario from a developing country.

Aim:Data on epidemiology and outcome in metastatic stomach carcinoma patients from India are scarce. We aimed to evaluate clinical features and treatment outcome in patients treated at our center.Materials and Methods:This is a single institutional review of metastatic gastric carcinoma patients treated between May 2011 and October 2016. Patients who received at least one cycle of chemotherapy were included for modified intent-to-treat survival analysis.Results:total of 143 patients were diagnosed with metastatic stomach carcinoma with a median age of 56 years (range: 29–86). The most common symptoms were abdominal pain in 112 (78%) patients. The most common site was body in 81 (57%) patients. Common site of metastasis was peritoneum in 86 (60%) and liver in (62%). Seventy-one (50%) patients were eligible for survival analysis. Common chemotherapy regimens were capecitabine-cisplatin in 27 (38%) and EOX in 22 (31%) patients. Survival status could not be assessed in 29 (41%) patients who lost to follow-up. After a median follow-up 9.7 months (range: 0.5–37.7), median progression-free survival (PFS) was 7.9 months (range: 0.5–23.9) and median overall survival (OS) was 12.2 months (range: 0.5–37.7). The Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2 and the presence of linitis plastica showed a trend toward inferior PFS (P = 0.052 and 0.053, respectively) only in univariate analysis. Female sex and ECOG PS ≥2 predicted inferior OS in both univariate and multivariate analysis (P = 0.012, 0.02 and 0.03 and 0.05, respectively).Conclusions:Platinum-based doublet chemotherapy was used in the majority of patients. The overall outcome was comparable to that of the available literature. Female sex and ECOG PS ≥2 predicted the inferior outcome.

Rationale and Design of the Strain Surveillance of Chemotherapy for Improving Cardiovascular Outcomes: The SUCCOUR Trial

ObjectivesThis study sought to evaluate the hypothesis that global longitudinal strain (GLS) guidance of cardioprotective therapy would improve cardiac function of at-risk patients undergoing potentially cardiotoxic chemotherapy, compared with usual care. BackgroundThe conventional criteria for diagnosis of chemotherapy-related cardiac dysfunction (CTRCD) are dependent on the recognition of heart failure symptoms and/or changes in left ventricular ejection fraction. However, the measurement variability of left ventricular ejection fraction necessitates broad diagnostic ranges, with the consequence of low sensitivity for CTRCD. Observational data have shown GLS to be a robust and sensitive marker to predict CTRCD and thereby guide the initiation of cardioprotective therapy, but these data are insufficient to justify changing the diagnostic criteria for CTRCD. MethodsThe SUCCOUR (Strain sUrveillance of Chemotherapy for improving Cardiovascular Outcomes) trial is an international multicenter prospective randomized controlled trial. Patients who are taking cardiotoxic chemotherapy (n = 320) with at least 1 risk factor will be randomly allocated into GLS- and ejection fraction–guided strategies. All participants will be followed over 3 years for the primary endpoint (change in 3-dimensional ejection fraction) and other secondary endpoints. ResultsAmong the first 185 patients (age 54 ± 13 years; 93% women) from 23 international sites, 88% had breast cancer, 9% had lymphoma, and 3% had other cancers. Heart failure risk factors were prevalent: 34% had hypertension and 10% had diabetes mellitus. The most common chemotherapy regimen during this study was the combination of anthracycline and trastuzumab. The baseline 3-dimensional left ventricular ejection fraction was 61 ± 4%, and GLS was 20.3 ± 2.5%. Of 93 patients followed up in the first year of the study, 10 had to withdraw for noncardiac reasons. Of 40 patients randomized to the GLS-guided arm, 15 have been started on cardioprotective therapy, whereas 4 of 46 patients in the ejection fraction–guided arm have been started on therapy. ConclusionsThe SUCCOUR trial will be the first randomized controlled trial of GLS and will provide evidence to inform guidelines regarding the place of GLS for surveillance for CTRCD. (Strain sUrveillance of Chemotherapy for improving Cardiovascular Outcomes [SUCCOUR]; ANZ Clinical Trials ACTRN12614000341628)

Comparison of the incidence of febrile neutropenia in obese and normal weight breast cancer patients receiving myelosuppressive chemotherapy and prophylactic pegfilgrastim.

Common breast cancer chemotherapy regimens are associated with a risk of febrile neutropenia, so prophylactic colony-stimulating factors are incorporated for high-risk patients. Filgrastim utilizes weight-based dosing; however, its sustained-release formulation utilizes fixed dosing. The purpose of this study is to determine whether obese breast cancer patients who receive pegfilgrastim are at increased risk of developing febrile neutropenia. This study is a single-center, retrospective chart review. Breast cancer patients were categorized as normal weight (body mass index < 30), overweight (body mass index 30-39), or obese (body mass index ≥ 40). A total of 442 eligible patients were identified between 1 July 2012 and 19 May 2016. Twenty-eight were included in the obese group. Twenty-eight patients from each non-obese group were randomly selected to make up the overweight and normal weight groups. Incidence of febrile neutropenia was 1, 2, and 2 of 28 in the normal weight, overweight, and obese research groups, respectively. Increased use of antibiotics was observed in the obese group as compared to the normal and overweight groups (2, 1, 1, respectively; p = 0.0005). Median number of days on antibiotics was statistically significantly higher in the obese group at 10 days compared to the normal and overweight groups at seven days ( p = 0.03). Obese patients are not at increased risk of febrile neutropenia. However, they may have a lower threshold for febrile neutropenia and require more antibiotics after chemotherapy. Clinical significance of these results cannot be determined given the small sample size, so further multicenter studies are required.

Maintaining Dose Intensity of Adjuvant Chemotherapy in Older Patients With Breast Cancer

IntroductionMaintaining the relative dose intensity (RDI) of adjuvant chemotherapy at ≥ 85% has been associated with improved treatment outcomes in early-stage breast cancer (ESBC). Increasing evidence has suggested that patients aged ≥ 65 years can maintain the optimal RDI for standard chemotherapy regimens. The present study investigated the RDI of newer adjuvant chemotherapy regimens in this demographic. Patients and MethodsWe retrospectively analyzed the data from 281 patients aged ≥ 65 years with a diagnosis of ESBC who had received adjuvant chemotherapy across 3 sites in Queensland, Australia from 2010 to 2015. The primary endpoint was the proportion of patients who had received an RDI of ≥ 85%. ResultsThe median age at diagnosis was 68 years (range, 65-85 years), with 36.3% aged > 70 years. The patient characteristics included tumor stage T3 or T4 in 17% and node-positive disease in 60%. The common chemotherapy regimens included docetaxel/cyclophosphamide (23%), 5-fluorouracil/epirubicin/cyclophosphamide plus docetaxel or paclitaxel (17%); Adriamycin/cyclophosphamide/weekly paclitaxel (38%); and docetaxel/carboplatin/trastuzumab (11%). Primary (15%) and secondary (54%) granulocyte colony-stimulating factor (G-CSF) was used. An RDI of ≥ 85% was achieved in 63% of the patients. Significant associations were noted between a reduced RDI and age ≥ 70 years (P < .001), Charlson comorbidity index ≥ 1 (P = .043), initial dose reductions (P = .01), secondary G-CSF use (P = .45), hospital admission (P < .001), and febrile neutropenia (P = .007). Treatment-related toxicities were the most common reason for noncompletion, with high rates of hospital admissions (46%) and febrile neutropenia (22%). ConclusionOur findings suggest that patients aged ≥ 65 years with ESBC can maintain an optimal RDI with modern chemotherapy regimens. Appropriate geriatric assessment and the use of supportive measures such as G-CSF could better assist select groups to maintain an optimal dose intensity.

Resveratrol, a natural polyphenol, prevents chemotherapy-induced cognitive impairment: Involvement of cytokine modulation and neuroprotection

Chemotherapy-induced cognitive impairment, also known as “chemobrain,” is a common side effect. The purpose of this study was to examine whether resveratrol, a natural polyphenol that has nootropic effects, could prevent chemobrain and its underlying mechanisms. Mice received three injections of docetaxel, adriamycin, and cyclophosphamide (DAC) in combination, a common chemotherapy regimen, at two-day intervals within one week. Resveratrol (50 and 100 mg/kg per day) was orally administered for three weeks, beginning one week before the DAC treatment. Water maze test and manganese-enhanced magnetic resonance imaging were used to evaluate animals' cognitive performance and brain neuronal activity, respectively. Blood and brain tissues were collected for measurement of cytokines, cytokine regulators, and biomarkers for neuroplasticity. DAC treatment produced a striking cognitive impairment. Cotreatment with 100 mg/kg resveratrol ameliorated DAC-induced cognitive impairment and decreases in prefrontal and hippocampal neuronal activity. Mice co-treated with both doses of resveratrol displayed significantly lower levels of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), but markedly higher levels of the anti-inflammatory cytokines IL-4 and IL-10 in several sera and brain tissues than those co-treated with vehicle. Resveratrol modulated the cytokine-regulating pathway peroxisome proliferator activated receptor (PPAR)-γ/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and protected against DAC-induced decreases in the expression of the neuroplasticity biomarkers, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), amino acid neurotransmitter receptors, and calmodulin-dependent protein kinase II (CaMKII). These results demonstrate the efficacy of resveratrol in preventing chemobrain and its association with cytokine modulation and neuroprotection.

Prognostic significance of nutritional risk index in patients with metastatic esophageal squamous cell cancer.

156 Background: It has been suggested that nutritional indicators predict the prognosis of esophageal cancer. Nutritional risk (NR) as prognostic factor evaluated by NR index (NRI) in metastatic esophageal squamous cell cancer (ESCC) has not been clarified. Methods: We retrospectively reviewed the data of consecutive patients (pts) with metastatic ESCC who received chemotherapy (CTx) as initial treatment at Shizuoka Cancer Center between April 2008 and December 2015. The selection criteria were as follows: histologically confirmed squamous cell carcinoma; no indication for curative resection or definitive chemoradiotherapy (dCRT); adequate organ function; no prior CTx, radiotherapy (RT) or chemoradiotherapy; no other advanced malignancies. NR was calculated by following formula: NRI = (1.489*serum albumin) + (41.7*present body weight [BW] / ideal BW). NR was classified into 4 groups according to NRI: major (NRI &lt; 83.5), moderate (NRI = 83.5-97.5), mild (NRI = 97.5-100), none (NRI &gt; 100). Multivariate analysis was carried out using cox proportional hazard to estimate the hazard ratio for overall survival (OS). Results: The patients’ characteristics of 138 pts who met the selection criteria were as follows: median age (range), 67 (33-86) years; male/female, 123/15; performance status (PS) 0/1/2, 62/68/8; number of metastatic sites 1/2/3/4, 55/56/23/4; smoking history -/+, 19/119; previous esophagectomy -/+, 118/20; median skeletal muscle index (range), 44.5 (27.8-63.2); median body mass index (range), 20.3 (14.3-27.4); NR major/moderate/mild/none 22/37/26/53; median serum C-reactive protein (CRP) level (range), 0.75 (0.01-20.48) mg/dL. The most common chemotherapy regimen used was fluoropyrimidine plus cisplatin (93%), and 70 patients (50%) received concomitant RT. Median OS was 4.6 months in pts with major NR and 11.8 months in others (p &lt; 0.001). Multivariate analysis for OS identified PS 2, female sex, metastatic sites &gt; 2, CRP ≥ 1mg/dL, and major NR independently associated with poor survival. Conclusions: Major NR calculated by NRI formula associated with poor survival in pts with metastatic ESCC.

SAPPHIRE: A randomized phase II study of mFOLFOX6 + panitumumab versus 5-FU/LV + panitumumab after 6 cycles of frontline mFOLFOX6 + panitumumab in patients with colorectal cancer.

729 Background: FOLFOX therapy, an infusion of 5-fluorouracil (5-FU) with leucovorin in combination with oxaliplatin (OXA), is a common first-line chemotherapy regimen for unresectable, advanced or recurrent colorectal carcinoma (CRC). However, long-term administration of OXA is associated with peripheral neuropathy (PN); decreasing treatment length of OXA may be beneficial without reducing its efficacy. Methods: Chemotherapy-naïve pts aged ≥20 yrs with RAS wild-type advanced/recurrent CRC were enrolled to receive 6 cycles of panitumumab (Pmab) + mFOLFOX6 once every 2 wks. Pts who completed 6 cycles of Pmab + mFOLFOX6 and confirmed no progressive disease were subsequently randomized 1:1 to continue to receive Pmab + mFOLFOX6 (arm 1) or Pmab + 5-FU/LV (arm 2). The primary endpoint was progression-free survival (PFS) rate at 9 mos after randomization. The threshold PFS rate was defined as 30%, and the expected rate was set at 50%, with a 90% power and a 1-sided alpha value of 0.10. In the primary analysis, a binomial test was conducted separately for each arm. This study was designed as a phase II randomized screening comparison study which does not use direct comparison for the primary analysis. Results: Of 164 enrolled pts who received initial Pmab + mFOLFOX6 treatment, 56 were randomized to arm 1 and 57 to arm 2. PFS rates at 9 mos after randomization were significantly higher than the defined threshold at 44.6% (80% CI, 36.4–53.2) in arm 1 and 47.4% (39.1–55.8) in arm 2. Median PFS after randomization was 9.1 (8.6–11.2) and 9.3 (6.0–13.0) mos, respectively. Grade ≥2 PNs occurred in 6 (10.7%) and 1 (1.8%) pts in arms 1 and 2, respectively. Serious AEs occurred in 14 (25.0%) pts in arm 1 and in 9 (16.7%) pts in arm 2. Conclusions: The results of this trial suggest that Pmab + 5-FU/LV after 6 fixed-cycles of Pmab + mFOLFOX6 may be a treatment option in pts with RAS wild type chemotherapy-naïve advanced/recurrent CRC. Pts treated with Pmab + 5-FU/LV had a lower occurrence of grade ≥2 PNs compared with Pmab + mFOLFOX6. Clinical trial information: NCT02337946.

Epidemiology of Clostridium difficile infection Among Patients with Newly Diagnosed or Relapsed Acute Leukemia: A Single-center Experience

BackgroundPatients undergoing treatment for hematologic malignancy are at a higher risk for developing Clostridium difficile infection (CDI). We sought to determine the epidemiology of toxigenic C. difficile (TCD) carriage and CDI incidence among patients undergoing with newly diagnosed or relapsed acute leukemia.MethodsSerial stool samples were collected from 92 patients with new or relapsed acute leukemia admitted at Memorial Sloan Kettering Cancer Center between August 26, 2011 to January 22, 2013. Only the first hospitalization during this time period was included. Screening was performed by toxigenic culture and polymerase chain reaction for tcdB gene regardless of symptoms of diarrhea. Genotyping was done by Multi Locus Sequence Typing (MLST). Acquisition of TCD, development of CDI, and associated clinical variables were recorded.ResultsA total of 92 patients were enrolled in the study. The mean age was 54.3 (median 57.5, range 21–86), 51 were male (55%). The majority (86, 93%) had newly diagnosed acute leukemia and 7% had relapsed disease. 60 patients (65%) had recent healthcare-related exposure, among these were 35 (38%) patients newly referred another facility. The most common chemotherapy regimen was Daunorubicin + Cytarabine in 71 subjects (77%). Systemic antibiotics of any duration during the same hospitalization were used in 89 patients (97%). Median length of stay (LOS) was 30.5 days (range 6–140 days).Among the 92 subjects, 17 developed CDI within 90 days (18%), 12 (71%) had CDI during the index admission. Five among these 12 had known TCD colonization, genotyping of colonizing and CDI strains from the same patients were identical for all patients. CDI in subsequent hospitalizations occurred in 5 patients, 4/5 were new acquisitions. One patient with TCD colonization never developed CDI.53 subjects (58%) underwent stem cell transplant at a median time of 4 months (range 2–19 months), 8 (15%) developed CDI within 30 days of the transplant admission.ConclusionCDI is exceedingly common among patients with acute leukemia. Acquisition of TCD and CDI occurs early in the treatment course. Approximately half of infections occur in patients with known TCD colonization. Extended LOS and high antibiotic usage are contributors to the high burden of CDI among this population.Disclosures All authors: No reported disclosures.

Metastatic stomach cancer: Real world scenario from a developing country.

e15569 Background: Data on epidemiology and outcome in metastatic stomach carcinoma patients from resource poor country is scarce. We aimed to evaluate clinical features and treatment outcome in patients treated at our center. Methods: This is a single institutional review of metastatic stomach carcinoma patients treated between May’2011 and October’2016. Patients with past history of adjuvant treatment were also included when they developed metastasis. Progression-free survival (PFS) was calculated from date of diagnosis of metastasis to date of disease progression. Patients who received at least one cycle of chemotherapy were included for a modified intent-to-treat survival analysis. Results: Total 143 patients were diagnosed with metastatic stomach carcinoma with median age of 56 years (range: 29-86) and male:female ratio of 92:51. Twenty-five (17%) patients received prior adjuvant therapy before developing metastasis. Commonest symptoms were abdominal pain in 112 (78%), weight loss in 72 (50%) and gastric outlet obstruction in 33 (24%) patients. Primary sites were proximal stomach in 44 (30%), body in 81 (57%) and distal stomach-pyloric region in 18 (13%) patients. Site of metastasis was peritoneum in 86 (60%), liver in 62 (43%), lung &amp; pleura in 22 (15%), ovary in 14 (10%), and bone in 12 (8%) patients, and 104 (75%) patients had &gt; 1 site of metastasis. Seventy-one (50%) patients were eligible for survival analysis. Common chemotherapy regimens were capecitabine-cisplatin in 27 (38%) and EOX in 22 (31%) patients. Survival status couldn’t be assessed in 29 (41%) patients who lost to follow-up. After a median follow-up 9.7 months (range: 0.5-37.7), median PFS was 7.9 months (range: 0.5 – 23.9) and median OS was 12.2 months (range: 0.5-37.7). ECOG performance status (PS) ≥2 and presence of linitis plastica showed a trend towards inferior PFS (p = 0.052 and 0.053, respectively) only in univariate analysis. Female sex and ECOG PS≥2 predicted inferior OS in both univariate and multivariate analysis (p = 0.012, 0.02 and 0.03 &amp; 0.05, respectively). Conclusions: Platinum based doublet chemotherapy was used in majority of patients. Overall outcome was comparable to that of the available literature. Female sex and ECOG PS≥2 predicted inferior outcome.

Describing the value of the most common first line NSCLC regimens in a real world setting.

9046 Background: We aim to describe clinical and economic outcomes of common chemotherapy regimens for first line therapy of metastatic non-small cell lung cancer (mNSCLC).The data are intended to help clinicians and patients understand the real world results for patients like themselves. Methods: This retrospective analysis used clinical data obtained from a prior authorization (PA) program for chemotherapy linked with administrative claims data from 6/1/2015 to 5/31/2016 from a large national managed care organization. Clinical data included cancer type, stage at diagnosis, biomarkers, treatment line and evidence of progression/relapse. Eligible patients were commercially insured members with a PA request for commonly used NCCN recommended regimens for first line therapy of mNSCLC. Outcomes, including duration of therapy, % of patients hospitalized and total cost of care were tracked from first claim for chemotherapy until end of treatment due to discontinuation, death or start of a second line, with remaining patients censored at 5/31/2016 or end of enrollment. Results: Of 830 mNSCLC patients, 498 (60%) completed first line therapy during the study period. 345 initiated one of the following: Carbo/cisplatin + pemetrexed (CA), Carbo/cisplatin + paclitaxel (CP), Carbo/cisplatin + bevacizumab + pemetrexed (CBA), nivolumab (N), and docetaxal (D). Outcomes are summarized in the Table. Conclusions: Patients treated with the five most commonly prescribed first line therapies for mNSCLC have much shorter duration of therapies (52-76 days) than reported in published clinical trials with a significant risk of hospitalization (18% -30%) and at substantial cost ($34,971 - $108,100). These data are an important consideration for the patient and clinician making treatment decisions in routine clinical practice and will become more valuable as the database grows over time. [Table: see text]

A stakeholder-driven approach to improve the informed consent process for palliative chemotherapy

ObjectivePatients often anticipate cure from palliative chemotherapy. Better resources are needed to convey its risks and benefits. We describe the stakeholder-driven development and acceptability testing of a prototype video and companion booklet supporting informed consent (IC) for a common palliative chemotherapy regimen. MethodsOur multidisciplinary team (researchers, advocates, clinicians) employed a multistep process of content development, production, critical evaluation, and iterative revisions. Patient/clinician stakeholders were engaged throughout using stakeholder advisory panels, featuring their voices within the intervention, conducting surveys and qualitative interviews. A national panel of 57 patient advocates, and 25 oncologists from nine US practices critiqued the intervention and rated its clarity, accuracy, balance, tone, and utility. Participants also reported satisfaction with existing chemotherapy IC materials. ResultsFew oncologists (5/25, 20%) or advocates (10/22, 45%) were satisfied with existing IC materials. In contrast, most rated our intervention highly, with 89–96% agreeing it would be useful and promote informed decisions. Patient voices were considered a key strength. Every oncologist indicated they would use the intervention regularly. ConclusionOur intervention was acceptable to advocates and oncologists. A randomized trial is evaluating its impact on the chemotherapy IC process. Practice implicationsStakeholder-driven methods can be valuable for developing patient educational interventions.

Cost minimization analysis of capecitabine versus 5-fluorouracil-based treatment for gastric cancer patients in Hong Kong

Background: EOX (epirubicin, oxaliplatin, Xeloda; capecitabine) and FOLFOX4 (5-fluorouracil (5-FU), leucovorin, oxaliplatin) are the common chemotherapy regimens used in the treatment of advanced gastric cancer (aGC) in Hong Kong. This study aimed to compare the costs of these therapies for aGC patients from both the healthcare and societal perspectives. It should be noted that, while FOLFOX4 is routinely administered in an outpatient setting in North America and Europe, inpatient setting is adopted in Hong Kong instead, incurring hospitalization cost as a result.Methods: Fifty-eight patients were identified from the electronic records in two public tertiary hospitals, with 45 and 13 receiving EOX and FOLFOX4 regimens, respectively. Healthcare cost was direct medical costs including drugs, clinic follow-up, hospitalization, diagnostic laboratories, and radiographs. Societal cost refers to indirect costs such as patient time and travel costs. Cost items were further classified as “expected” or “unexpected”. All cost data was expressed in US dollars.Results: Patients in the EOX and FOLFOX4 arm received an average of 5.3 and 7.8 cycles of treatment, respectively. The capecitabine-based regimen group had a higher expected medication cost per cycle when compared to the 5-FU-based treatment group (US$290.3 vs US$66.9, p < .001), but lower expected hospitalization costs (US$76.9 vs US$1,269.2, p < .001). The total healthcare cost and total societal cost per patient was reduced by 67.2% (US$5,691.9 vs US$17,357.4, p < .001) and 25.3% (US$3,090.5 vs US$4,135.1, p = .001), respectively, in the capecitabine-based regimen group. Sensitivity analyses based on full cycle regimen costs and net capecitabine or 5-FU/leucovorin costs still showed EOX to be less costly than FOLFOX4.Conclusion: The capecitabine-based regimen, EOX, was found to generate significant cost saving from both the healthcare and societal perspectives in regions in which FOLFOX4 is given in an inpatient setting.

Abstract P2-11-01: Non interventional study with netupitant/ palonosetron (NEPA) as CINV prophylaxis in highly or moderately emetogenic chemotherapy

Abstract Background Nausea and Vomiting due to cancer therapy is still a problem for patients and physicians and therefore an ongoing item of research in oncology. International antiemetic guidelines (ASCO, NCCN, MASCC/ESMO) have been published and new drugs are introduced into the market. The fixed oral combination of the NK1-receptor antagonist (RA) netupitant and the 5-HT3-RA palonosetron (NEPA) was recently approved in US and EU for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) in cancer patients receiving cisplatin-based highly emetogenic (HEC) or moderately emetogenic chemotherapy (MEC). The MASCC guidelines 2016 recommend a triple combination of 5-HT3- and NK1-RA and dexamethasone given on day 1 for patients receiving HEC, anthracycline / cyclophosphamide (AC)-containing chemotherapy as well as for carboplatin-based MEC for the prevention of chemotherapy-induced nausea and vomiting (CINV). Objectives The primary endpoint of this non interventional study is the evaluation of quality of life in adult cancer patients receiving NEPA for CINV prevention in MEC or HEC. Secondary endpoints are efficacy and safety of NEPA. Methods This non-interventional study evaluates CINV prophylaxis with NEPA and QoL in 2500 cancer patients receiving single day or two day MEC or HEC in an ambulatory setting in German cancer hospitals and specialized cancer practices. NEPA is prescribed in accordance with the EU marketing authorization. Quality of life is recorded by FLIE questionnaires. Efficacy - measured as complete response (CR, no vomiting, no rescue medication) –as well as additional medication, safety and adverse events (AEs) are documented by an online questionnaire filled by the physician and a patient diary. 3 consecutive chemotherapy cycles are documented online using the ODM QuaSi documentation system. All specifications in the online documentation must be verifiable. Results 700 patients from 175 centers (93 gynaecologic oncology, 79 medical oncology, 3 urologic oncology) are included to date. The majority of patients were women (88.7%). 71% of all patients had breast cancer. 92.6% had an ECOG performance status of 0-1. 77.6% received (neo)adjuvant chemotherapy. Most common chemotherapy regimens were AC-based regimens (53.9%), carboplatin-based regimens (15.9%) and cisplatin-based regimens (12%). Efficacy data are available for 486 patients in cycle 1 and 350 patients over 3 cycles. During 3 consecutive chemotherapy cycles, 89% of patients had a CR on day 1 as recorded by patient diaries. In the delayed phase (days 2-5), 85% of patients had a CR. 93% recorded no vomiting during the entire 5 days at risk following chemotherapy and 69% reported no or only mild nausea. &amp;gt; 90% of the medical staff rated the efficacy of the CINV-prophylaxis with NEPA as good or very good over 3 cycles. Adverse events (AE), mostly constipation were rare and mild and only of grade 1 or 2. No serious AEs were observed. Summary NEPA is a safe and efficacious option for the prophylaxis of nausea and vomiting in highly and moderately emetogenic chemotherapy. Citation Format: Schilling JP, Karthaus M, Klare P, Guth D, Ortner PA. Non interventional study with netupitant/ palonosetron (NEPA) as CINV prophylaxis in highly or moderately emetogenic chemotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-11-01.

Two randomized, placebo-controlled phase 3 studies of ruxolitinib (Rux) + capecitabine (C) in patients (pts) with advanced/metastatic pancreatic cancer (mPC) after failure/intolerance of first-line chemotherapy: JANUS 1 (J1) and JANUS 2 (J2).

343 Background: The JAK-STAT pathway plays a role in the pathogenesis of PC. In a phase 2 study, the JAK1/2 inhibitor Rux + C improved OS vs C alone in mPC pts with evidence of systemic inflammation. Methods: In two phase 3 studies, advanced/mPC pts with only 1 prior chemotherapy regimen and C-reactive protein &gt; 10mg/L were randomized to 21-day cycles of Rux 15 mg BID + C 2000 mg/m2/d (day 1-14) vs placebo (Pb) BID + C 2000 mg/m2/d (day 1-14). The primary endpoint was OS. The studies were terminated early based on efficacy findings of a planned interim analysis for J1, with J2 enrollment incomplete. Results: 321 pts were randomized in J1 and 86 in J2. The median age was similar between groups (Rux + C vs Pb + C): J1, 68 vs 67 yrs; J2, 68 vs 69 yrs. The most common prior chemotherapy regimens were gemcitabine (gem) + nab-paclitaxel (J1: 50% vs 51%, J2: 42% vs 37%), gem alone (J1: 24% vs 21%, J2: 28% vs 33%). Median study treatment durations were 42 d for both Rux and Pb in J1; 40 d for Rux and 43 d for Pb in J2. Discontinuations were mainly due to disease progression (J1: 62% vs 65%, J2: 51% vs 58%), AEs (J1: 4% vs 10%, J2: 12% vs 12%) or death (J1: 8% vs 5%, J2: 7% vs 5%). Rux + C did not show a benefit over C alone in OS or PFS (see Table). Overall response rates were &lt; 5% in each treatment group (NS).The most common grade 3/4 non-hematologic AEs were abdominal pain (J1: 7% vs 14%; J2: 14% vs 5%), palmar-plantar erythrodysesthesia syndrome (J1: 7% vs 4%; J2: 0% vs 12%), pulmonary embolism (J1: 4% vs 3%; J2: 10% vs 5%), dyspnea (J1: 2% vs 2%; J2: 10% vs 2%) and vomiting (J1: 5% vs 5%; J2: 2% vs 12%). The most common new/worsening hematologic labs abnormalities of grade 3/4 included: anemia (J1: 20% vs 6%; J2: 11% vs 8%) and lymphopenia (J1: 17% vs 9%; J2: 16% vs 8%). Conclusions: When added to C, Rux was well tolerated but did not improve clinical outcomes in the second-line treatment of mPC pts. Clinical trial information: NCT02117479 and NCT02119663. [Table: see text]