Pulsed high-dose erlotinib with gemcitabine as second-line therapy for pancreatic adenocarcinoma.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 421-421
Author(s):  
Christopher Larson ◽  
Tony R. Reid

421 Background: The options for treatment of pancreatic cancer follow progression on first line therapy are limited and associated with significant toxicity. Erlotinib has been approved for treatment of pancreatic cancer in first-line therapy. We conducted a phase I dose-escalation trial of erlotinib in combination with gemcitabine for patients that had failed first-line therapy. Erlotinib was administered by a novel pulse-dose schedule where the drug was given orally for 3 days every two weeks. Purpose: Assess the safety and determine a recommended phase II dose for pulsed high dose erlotinib in combination with gemcitabine for pancreatic cancer, and obtain preliminary data on activity. Methods: Patients with pancreatic cancer that progressed on or after first-line therapy were treated in a dose escalation study with erlotinib at 750 to 2,000 mg daily for three days every two weeks in combination with weekly gemcitabine at 1,000 mg/m2 for three weeks on and one week off. Results: No dose limiting toxicities were encountered and erlotinib-induced rash was mild and transient. Median overall survival was 6.7 months and 12-month overall survival was 27%. Progression free survival but not overall survival was longer in patients who did not previously receive gemcitabine. Rash was not associated with longer survival. Conclusions: The recommended phase II dose is erlotinib 2,000 mg daily for three consecutive days every two weeks in combination with gemcitabine. Tolerability was excellent, and outcomes were better than expected for second-line therapy in pancreatic cancer. Further studies are warranted, both as therapy after first-line and as first-line therapy for patients unable to tolerate more aggressive regimens. Clinical trial information: NCT02154737.

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1507-1507
Author(s):  
Rami S Komrokji ◽  
Maria G. Corrales-Yepez ◽  
Najla H Al Ali ◽  
Eric Padron ◽  
Jeffrey E Lancet ◽  
...  

Abstract Introduction Lenalidomide (LEN) is the standard of care for treatment of transfusion dependent lower risk myelodysplastic syndromes (MDS) with chromosome 5q deletion (del 5q). In the MDS-002 study, 26% of lower risk transfusion dependent MDS patients became red blood cell transfusion independent after LEN treatment. National Comprehensive Cancer Network (NCCN) clinical guidelines list LEN as a second line treatment alternative for transfusion dependent anemia in lower risk non-del 5q MDS after azanucleosides failure. The response rate to LEN after azanucleosides failure, however, is not known given that the MDS-002 study preceded FDA approval of azanucleosides. To address the best sequence of LEN to optimize response potential in lower risk MDS, we examined the response rates to LEN in non-del 5q lower risk MDS when offered as first line after (erythroid stimulating agents) ESA's or after azacitidine failure. Methods This was a retrospective study conducted using the Moffitt Cancer Center (MCC) MDS database. We identified patients with lower risk MDS who received both LEN and azacitidine as first or second line therapy after erythroid stimulating agents. Lower risk MDS was defined according to the international prognostic scoring system (IPSS) Low or intermediate-1 (int-1) risk groups. The primary endpoint was to compare rates of erythroid hematological improvement (HI-E) between the group of patients who received LEN as first line therapy followed by azacitidine as second line (LEN 1st line group) and those who received LEN as second line therapy after azacitidine (LEN 2nd line group). HI was defined according to international working group criteria (IWG 2006). Chi- square test was used for categorical variables, T-test was used for continuous variables, and Kaplan Meier estimates for overall survival. All analyses were conducted using SPSS statistical software (IBM version 21) Results We identified 63 patients who received both azacitidine and LEN as first and second line where 37 patients were in group 1 (LEN 1st line) and 26 patients were in group 2 (LEN 2nd line). Baseline characteristics between the two groups are summarized in Table-1. There were no statistically significant differences between the 2 groups in terms of mean age at diagnosis, gender, WHO subtype, revised IPSS, or mean blood counts. The majority of patients had refractory cytopenia with multilineage dysplasia (RCMD) and had low risk revised IPSS . The rate of HI-E was 38% (n=14) among LEN 1st line group compared to 12% (n=3) in LEN 2nd line group. (p=0.04). There was no difference in overall survival (OS) among the two groups with a median OS of 104 months and 87 months, respectively, p=0.55. There was no difference in AML transformation rate, 5.4% (n=2) and 11% (n=3) among the two groups, respectively, p=0.33. There were no differences in response rates to azacitidine among the two groups. Among the Len 1st line group response to 2nd line azacitidine was 38% (n=14) compared to 35% (n=9) among those who received azacitidine as first line followed by LEN as 2nd line. (p=0.69). Conclusion LEN yields a higher rate of HI-E in non-del 5q lower risk MDS when used as first line therapy. If validated in a larger cohort, LEN should be considered for 1st line therapy after ESAs rather than after azacitidine failure. Responses to azacitidine were similar among the two groups, indicating no adverse effect of LEN on azacitidine response. Disclosures: Komrokji: Celgene: Research Funding, Speakers Bureau. Off Label Use: use of lenalidomide in non del 5q. Lancet:Celgene: Research Funding. List:Celgene: Research Funding.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1790-1790
Author(s):  
Petra Obrtlikova ◽  
Anna Jonasova ◽  
Magda Siskova ◽  
Eduard Cmunt ◽  
Adela Berkova ◽  
...  

Abstract Abstract 1790 Background: The immunochemotherapy regimen composed of fludarabine, cyclophosphamide and rituximab (FCR) has emerged as highly effective frontline or second line therapy for chronic lymphocytic leukemia (CLL). This regimen may be however associated with prolonged cytopenia and the risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Aims and methods: In our retrospective single center analysis, we evaluated the efficacy and the toxicity of FC or FCR regimen in unselected population of CLL patients with treatment indication. The overall survival (OS) and progression free survival (PFS) was calculated for all patients as intent to treat analysis. The prolonged cytopenia was defined as cytopenia (grade 2–4 according to CTCAE v.4 ) developing during of after the last cycle of FC/FCR and persisting two or more months. Cytopenia was evaluated in patients with follow-up at least 6 months after this treatment. Patients were excluded from analysis of cytopenia if they underwent immediate other treatment (antibody maintenance, high dose therapy with autologous stem cell transplantation (ASCT) consolidation, or they received other therapy due to unsatisfactory response to FCR). Patients with missing laboratory data after FC(R) were also excluded. Kaplan Maier curves for PFS and OS were calculated and log rank test was used for survival comparison. Results: Altogether, 252 patients started the treatment with FC or FCR in the years 2000–2012 at our institution. There were 86 (34%) women and 166 (66%) men with a median age of 62 years (31–87) at the time of FC(R) therapy. 52 (21%) pts received FC regimen, including 40 pts treated in first line therapy and 12 pts in second line therapy. FCR therapy was administered in 200 pts (79%): 153 pts received FCR as first line therapy, 38 pts as second line therapy and 8 pts as third or fouth line therapy. The median number of FC cycles was 5 (1–8) with or without R. The estimated OS for the first line therapy was 87,5% in FCR group vs 80% at 3y in FC group (p ns) (Hallek,CLL8: 87% vs 83%) and PFS was 70% in FCR group vs 50% in FC group (p=0,004) with the median of follow-up 45 months. Altogether 184 pts fulfill the criteria for cytopenia analysis. The most frequent immediate subsequent therapy considered as exclusion for this analysis was ASCT consolidation (n 20). Out of 184 pts, 146 recieved FC(R) as 1st line treatment and 38 subsequent therapy. The prolonged cytopenia was observed in 54 pts (29%), 42 (29%) in 1st line group and 12 (32%) in subsequent line group. Median duration of cytopenia was 8 m (2–65), 29 out of 54 patients have had persistent cytopenia at the time of last follow up. The cumulative probability to develop cytopenia was 30.3% at 2y among all pts and 29.7% among first line FCR treated pts. There was no significant difference between FC and FCR treated pts. Eleven pts developed MDS/AML, 7 cases were observed in the followed group of 184 pts (with probability 6.1% at 6y), in all cases the cytopenia preceded the MDS onset, 6y probability to develop MDS was 25.2% for patients who develop prolonged cytopenia after FC(R). Moreover 2 MDS and 1 AML were observed among 20 pts treated with ASCT (6y probability 5.6%, 8y probability 22.5%). The OS probability from 1stcycle of FC(R) was significantly better for pts without cytopenia (75.5% vs 57.5% at 5y, p<0.005), nonsigificant trend was observed if only first line FCR pts were analyzed (88% vs 85%). The median survival for the MDS pts from the time of MDS dg was 6 months only. Conclusions: Although the FCR is the best available standard treatment option for CLL pts, it is associated with prolonged cytopenia in 30% of cases. These patients with prolonged cytopenia afte FC(R) have considerably high probability (25.2%) to develop MDS and they have worse OS compared to pts without cytopenia. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4237-4237
Author(s):  
Asim F Belgaumi ◽  
Asem Bukhari ◽  
Mohammed Al-Mahr ◽  
Amal Al-Seraihy ◽  
Hazem Mahmoud ◽  
...  

Abstract Abstract 4237 Although the outcome of first line therapy for childhood ALL has improved significantly, the results of second line therapy remains suboptimal. The most important predictive factors identified for second line therapy are timing and site of relapse; early relapse and bone marrow (BM) involvement invoking poorer outcomes. At our institution we have utilized a risk stratified therapeutic strategy for relapsed/refractory ALL which includes these factors. Re-induction for patients with first remission (CR1) duration of <18 months or those with remission failure was with high dose cytarabine (HDAraC) containing regimens, most often with idarubicin (Ida). For patients with CR1 >18 months, we utilized a standard 4-drug (prednisone, vincristine, daunomycin, asparaginase [PVDA]) induction regimen. Patients who relapsed in the BM while on chemotherapy or within 1 year of being off therapy were eligible for hematopoietic stem cell transplantation (SCT) after achieving CR, as were patients with isolated extra-medullary relapse with CR1 <18 months. Patients with late relapse were treated with post consolidation maintenance chemotherapy alone. Data collected prospectively in our database were reviewed. ALL patients who relapsed after receiving first line therapy at our institution and those who were referred to us at first relapse were included in this analysis. Only overall survival (OS) is presented as all patients who failed to achieve a CR or relapsed after achieving CR eventually died regardless of further therapeutic interventions. Fifty-nine patients with ALL failed their first line therapy between January 1, 2005 and May 31, 2011. There were four induction failures and 55 relapses. These 59 patients included 39 males; 53 of the patients had B-cell ALL and 6 had T-cell ALL. The age at original diagnosis ranged from 0.55 to 13.8 years (mean 6; median 4.8; SEM 0.50) whereas the age at first failure ranged from 0.68 to 16.4 years (mean 8.0; median 7.8; SEM 0.50). 36/55 (65.5%) relapses occurred on first line chemotherapy, 17 (30.9%) after completion of therapy and 2 (3.6%) following SCT. For the relapsed patients, the duration of CR1 ranged from 0.09 to 9 years (mean 2.0; median 1.7; SEM 0.22); 24 (44.4%) patients relapsed less than 18 months from CR1. 36 (61%) patients had isolated BM relapse, 13 (22.1%) had isolated extra-medullary (7 CNS; 6 testicular) and the remaining 10 had BM with other sites. Twenty four patients (40.7%) were re-induced with HDAraC/Ida (HIda), 28 (47.5%) with PVDA, 4 (6.8%) Fludarabine/AraC (FA) and 3 did not receive any second line therapy. For those who were treated 37 (62.7%) achieved a CR; 13 of the 19 patients who did not achieve CR with second-line therapy received third-line induction therapy (9 FA; 1 HIda; 1 VM26/AraC; 1 PVDA; 1 VP/CTX) and 7 (53.8%) achieved CR. The overall survival for all 59 patients at 2 years is 45.3%; for those who achieved CR the overall survival at 2 years is 64.7%. When we compared those patients who had CR1 durations >18 months with those who were induction failures or had CR1 duration <18 months, we found no significant difference in CR2 induction rates (76.7% v. 80%; p=1.0), nor in OS (56.9% v. 34.5% at 2 years; p=0.14). CR induction rates did not change when we further categorized CR1 duration into 18 months, 18–36 months and >36 months (80% v. 72.2% v. 80%; p=0.74). However, the OS was significantly higher for the >36 month group (83.3%; p=0.023) when compared to the other 2 groups (38.7% and 38.4%, respectively). In patients with <36 months of CR1, HSCT resulted in a significantly improved OS as compared to chemotherapy alone (51.4% v. 30.9 at 2 years; p=0.05). For those patients who achieved a CR2 there was no difference in the OS between those who underwent HSCT v. those who continued on chemotherapy (68% v. 58.5% at 2 years; p=0.33). Patients who achieved a CR after 2nd line therapy fared much better than those who achieved a CR after 3rd line therapy (25/36 [69.4%] alive v. 2/7 [28.6%] alive; OS at 2 years 68.3% v. 29.2%; p=0.06). In conclusion, we believe that this risk stratified approach to the treatment of relapsed/refractory ALL in children is effective. While the majority of the patients can be re-induced into remission, maintenance of the remission is dependent on the duration of CR1; patients with late relapse do as well as treatment naïve patients. Increased intensity induction therapy for early relapses and SCT for patients with <36 months of CR1 may be beneficial. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Vol 22 (3) ◽  
pp. 142-148
Author(s):  
L. V. Bolotina

Throughout the last 10 years, liver cancer mortality rate in the Russian Federation consistently exceeded the morbidity rate, which is related to the complexity of early diagnostics, absence of effective screening and oncological alertness of allied-profession doctors. In the situation when late disease intelligence does not frequently allow radical treatment, palliative methods remain the only option of survivability enhancement and improving the patients quality of life. Lenvatinib was approved as the first-line drug in the treatment of unresectable hepatocellular carcinoma based on the data of the REFLECT trial, in which the drug demonstrated achieving the patients overall survival (OS) comparable to the activity of sorafenib (13.6 months for lenvatinib vs 12.3 months for sorafenib; hazard ratio HR 0.92; 95% confidence interval CI 0.791.06). At the same time, significant inferiority of lenvatinib was observed for secondary endpoints: progression-free survival PFS (7.4 months for lenvatinib vs 3.7 months for sorafenib; HR 0.66; 95% CI 0.570.77;р0.0001), time to progression (8.9 months for lenvatinib vs 3.7 months for sorafenib; HR 0.63; 95% CI 0.530.73;р0.0001) and objective response rate ORR (24.1% for lenvatinib vs 9.2% for sorafenib). The further analysis of the results of the REFLECT study revealed the additional factors impacting patients survival, such as the level of a-fetoprotein (AFP) before treatment, treatment ORR, performance of subsequent antitumor therapy and procedures after completion of the target first-line therapy. In patients responding to lenvatinib in the first line and further receiving any second-line therapy, the mOS was 25.7 months as compared with the median overall survival (mOS) of 22.3 months in patients responding to sorafenib and receiving further second-line therapy. Additionally, in responders switching from lenvatinib to sorafenib, the mOS was 26.2 months. In the recently published comparative study of lenvatinib and transarterial chemoembolization on the BCLC B stage, inferiority of lenvatinib was demonstrated in terms of OS, PFS and ORR in certain patient categories. Considering the data obtained in the REFLECT population, where in patients achieving the RR to the first-line treatment with lenvatinib and further receiving the local antitumor procedures the mOS increased to 27.2 months (95% CI 20.729.8), prescribing target and locoregional therapy in certain cases in this very sequence is possible. The recently published data about administration of lenvatinib outside of the inclusion criteria for the REFLECT trial, have proved the efficacy and safety of this drug administration in real clinical practice, thus significantly expanding our understanding of the key role of lenvatinib in the first-line treatment of unresectable hepatocellular carcinoma.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2936-2936
Author(s):  
Mark Danese ◽  
Robert Griffiths ◽  
Michelle Gleeson ◽  
Tapashi Dalvi ◽  
Jingyi Li ◽  
...  

Abstract Background DLBCL is the most common subtype of non-Hodgkin's lymphoma. Approximately 50% of DLBCL patients are over age 65. Patterns of care and outcomes in older patients receiving second-line therapy for DLBCL have not been well-characterized. Objective We analyzed patterns of care, overall survival and costs of care in a cohort of older DLBCL patients receiving second-line therapy. Methods Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we identified a cohort age ≥66 with DLBCL diagnosed between 2000 and 2007. Patients had to receive first-line therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or a CHOP-like regimen, with or without rituximab. Second-line treatment was defined as either (a) ≥1 new agents < 90 days after discontinuing all first-line agents (refractory disease), or (b) ≥1 agents (including first-line agents) ≥90 days after completion of first-line therapy (relapsed disease). Rituximab monotherapy was excluded (n=736). Patients were enrolled from 12 months prior to diagnosis and followed through 12/31/2009. Observation ended at death, change from coverage, or 12/31/2009. We reviewed the therapies of each patient and classified them into 1 of 3 groups: aggressive, conventional, or palliative. Direct costs to Medicare were calculated using paid amounts over the 24-month period after initiating second-line therapy, weighted to account for censoring, and inflated to 2009 US dollars. Results There were 5,716 first-line DLBCL patients of whom 632 (11%) received second-line therapy (206 refractory and 426 relapsed). The most common aggressive regimens were methotrexate (n=60), [carboplatin, cyclophosphamide and etoposide (n=54)] and [cisplatin, cytarabine, and etoposide (n=23)]. The most common conventional regimens were [cyclophosphamide, doxorubicin, and vincristine (n=74)], [cyclophosphamide and etoposide (n=31)]. The most common palliative regimens were etoposide (n=68), [cyclophosphamide and vincristine (n=56)], fludarabine (n=26), and gemcitabine (n=25). Median survival was 13.4 months. Overall, survival was not statistically significantly different among the different treatment approaches in multivariate-adjusted survival models. However, patient characteristics differed significantly between these treatment groups with patients receiving aggressive treatment being younger than in the palliative treatment group (>80 years: 9.1% vs 30.6%; p<0.0001). Similarly refractory patients were more frequent in the aggressive vs. conventional treatment group (53.4% vs. 11.3%; p<0.0001). Significant factors affecting survival included female gender (hazard ratio [HR] 0.65, 95% CI 0.53-0.80), absence of B symptoms at diagnosis (HR 0.69, 95% CI 0.53-0.89), and presence of anemia at diagnosis (HR 1.26, 95% CI 1.02-1.55. Multivariate adjusted, cumulative 24-month costs for the reference group for all model variables was $117,442 (95% CI $78,270 to $156,615). Significant factors that modified this cost were age 75-79 (relative to age 66-69; $-28,860), age ≥80 ($-42,262), extranodal involvement at diagnosis ($-15,421), and anemia at diagnosis ($+23,047). Conclusions Second-line therapy for refractory and relapsed DLBCL was associated with high mortality and costs in the Medicare population. While selection bias limits comparison of aggressive vs. conventional therapies, our findings suggest a substantial unmet need in the second-line setting. Disclosures: Danese: Genentech: Consultancy, Research Funding; Medimmune: Consultancy, Research Funding; Amgen: Consultancy, Research Funding. Griffiths:Amgen, Inc.: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; MedImmune: Consultancy, Research Funding. Gleeson:Amgen, Inc.: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; MedImmune: Consultancy, Research Funding. Dalvi:Medimmune: Employment, stock Other. Li:Medimmune: Employment, stock Other. Deeter:Medimmune: Consultancy, Employment, stock Other.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S680-S681
Author(s):  
Carly Heck ◽  
Judith Martin ◽  
Marcia Kurs-Lasky

Abstract Background Background: Antibiotic resistance is a major public health concern. A modifiable intervention is outpatient antibiotic stewardship. The goal of this study was to review the electronic health records (EHR) of children diagnosed with community acquired pneumonia (CAP) to compare patients who received non-guideline concordant therapy with those prescribed recommended therapy. Methods Methods: This was a retrospective chart review of 300 children (6 months to 6 years old) with an outpatient diagnosis of CAP between July 2017 and June 2019. 45 Children’s Hospital of Pittsburgh (CHP) and UPMC Children’s Community Pediatrics (CCP) practices were included. CHP practices are academic-based with trainees involved in visits, while CCP practices do not include trainees. First-line recommended therapy was defined as amoxicillin, second-line therapy as azithromycin or amoxicillin-clavulanate, and all other prescriptions were defined as other. Patients prescribed first-line therapy were compared to patients with second-line therapy or other. If first-line therapy was not prescribed, the EHR was manually reviewed for justification. If drug allergy was listed, the medication allergy and type of reaction were recorded. Results Results: In this study the minority of children (43%) were prescribed first-line therapy. This group was younger (57 vs. 63 months of age), more likely to be Non-white (80%), and seen at the CHP locations than those prescribed non-guideline concordant therapy. The average symptom duration was shorter, heart rate and respiratory rate were higher and the presence of fever was more common in the first-line therapy group. Justification for non-guideline therapy was most often reported as to provide coverage for atypical organisms. The most common drug allergy recorded was amoxicillin, and urticaria with unknown timing was the most common type of reaction. Demographics Comparison Results Justification for Second-line / Other Therapy and Drug Allergy Results Conclusion This project observed a high proportion of children being prescribed non-guideline concordant therapy for a diagnosis of CAP. Age, race, practice location, and severity of illness measures showed a statistically significant difference between groups. This study highlights the importance of education which reviews the current guidelines and the most likely pathogens for children with CAP. Disclosures All Authors: No reported disclosures


2004 ◽  
Vol 22 (7) ◽  
pp. 1209-1214 ◽  
Author(s):  
Axel Grothey ◽  
Daniel Sargent ◽  
Richard M. Goldberg ◽  
Hans-Joachim Schmoll

Purpose Fluorouracil (FU)-leucovorin (LV), irinotecan, and oxaliplatin administered alone or in combination have proven effective in the treatment of advanced colorectal cancer (CRC). Combination protocols using FU-LV with either irinotecan or oxaliplatin are currently regarded as standard first-line therapies in this disease. However, the importance of the availability of all three active cytotoxic agents, FU-LV, irinotecan, and oxaliplatin, on overall survival (OS) has not yet been evaluated. Materials and Methods We analyzed data from seven recently published phase III trials in advanced CRC to correlate the percentage of patients receiving second-line therapy and the percentage of patients receiving all three agents with the reported median OS, using a weighted analysis. Results The reported median OS is significantly correlated with the percentage of patients who received all three drugs in the course of their disease (P = .0008) but not with the percentage of patients who received any second-line therapy (P = .19). In addition, the use of combination protocols as first-line therapy was associated with a significant improvement in median survival of 3.5 months (95% CI, 1.27 to 5.73 months; P = .0083). Conclusion Our results support the strategy of making these three active drugs available to all patients with advanced CRC who are candidates for such therapy to maximize OS. In addition, our findings suggest that, with the availability of effective salvage options, OS should no longer be regarded as the most appropriate end point by which to assess the efficacy of a palliative first-line treatment in CRC.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-15
Author(s):  
Ali McBride ◽  
Daniel O. Persky

Introduction: The choice of initial therapy in follicular lymphoma can be a key determinant in future therapy, as irreversible toxicities with first line regimens can impact the patient's ability to tolerate future treatment. Minimizing drug exposure will result in less frequent occurrence of significant adverse events and associated treatment costs. In the era of COVID-19 pandemic, there is additional benefit to minimizing the number of patient visits and hospital admissions. Limited information exists related to the outcomes and associated costs of existing treatment sequences. Additionally, treatment administration at different types of clinical sites results in varied reimbursement models, making informed evaluation of clinical and financial evidence challenging. Methods: The current study applies a budget impact model methodology in order to describe the associated impact of treatment selection and sequencing on outcomes and costs in the treatment of relapsed or refractory low-grade follicular lymphoma in first line therapy followed by Consolidation and also in first line therapy to second line therapy. Key model inputs included: Number of treatment cycles, number of days a treatment was received, duration of response (DOR), rate of side effects and associated costs, and total treatment costs, including drugs, medical treatment, laboratory testing and adverse event costs. Treatment outcomes were based on the published literature that summarized the overall response rate, median DOR, and toxicity. Treatment regimen costs were evaluated based on payer pricing, Wholesale Acquisition Cost (WAC), Average Selling Price (ASP) and Average Wholesale Price (AWP) and modified to adjust for weight-based dosing and negotiate payer reimbursement rates. Associated medical costs for medical treatment and supportive care were estimated using current Medicare fee schedule rates. Included were seven options for first line therapy of follicular lymphoma from 2020 NCCN Guidelines - (Bendamustine + rituximab (BR); Bendamustine + Obinutuzumab (OB); CHOP rituximab (RCHOP); CHOP + Obinutuzumab (OCHOP); CVP+ rituximab (RCVP); CVP + Obinutuzumab (OCVP); Lenalidomide + rituximab (R2)), followed by three for Consolidation (Rituximab maintenance (RM); Obinutuzumab maintenance (O); Radioimmunotherapy (RIT with 90 Y-ibritumomab tiuxetan (Y90-IT, Zevalin)) and three Second Line therapy options (RIT; Lenalidomide only; Lenalidomide + Obinutuzumab (LO)). Results: The treatment sequence of first line BR followed by Consolidation with RIT Y90 (Zevalin) had the longest predicted DOR (2586 days). The associated treatment sequence costs were $212,485 for BR followed by Y90-IT, compared with $233, 388 for BR followed by rituximab maintenance, which had a predicted DOR of 2478 days. The predicted DOR for treatment sequences starting with OCHOP, OCVP and RCHOP and followed by RIT with Y90-IT was approximately 1000 days less than BR followed by Y90-IT for a cost difference of $4,421, $12,914 and $25,826, respectively. The treatment sequence of first line BR followed by Second Line RIT Y90-IT had the second longest predicted DOR of 2586 days at costs of $212,485, compared to 2778 days for BR followed by LO, at a total sequence costs of $796,695. Conclusion: The use of Y90-IT in Consolidation or Second Line treatment demonstrated desired patient outcomes at one of the lowest cost profiles. Additionally, Y90-IT administration can be completed in only two clinic visits, reducing patient travel and contact, improving safety in an era of COVID-19 precautionary measures and reducing cost. Figure 1. Duration of Response and Total Sequence Costs for Twelve First Line to Consolidation and First Line to Second Line Treatment Regimens. Disclosures McBride: Merck: Speakers Bureau; Coherus BioSciences: Consultancy, Speakers Bureau; Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy; MorphoSys: Consultancy; Sandoz: Consultancy.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hironaga Satake ◽  
Koji Ando ◽  
Eiji Oki ◽  
Mototsugu Shimokawa ◽  
Akitaka Makiyama ◽  
...  

Abstract Background FOLFOXIRI plus bevacizumab is used as a first-line therapy for patients with unresectable or metastatic colorectal cancer. However, there are no clear recommendations for second-line therapy after FOLFOXIRI plus bevacizumab combination. Here, we describe our planning for the EFFORT study to investigate whether FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC. Methods EFFORT is an open-label, multicenter, single arm phase II study to evaluate whether a FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC. Patients with unresectable or metastatic colorectal cancer who received FOLFOXIRI plus bevacizumab as a first-line therapy will receive aflibercept and FOLFIRI (aflibercept 4 mg/kg, irinotecan 150 mg/m2 IV over 90 min, with levofolinate 200 mg/m2 IV over 2 h, followed by fluorouracil 400 mg/m2 bolus and fluorouracil 2400 mg/m2 continuous infusion over 46 h) every 2 weeks on day 1 of each cycle. The primary endpoint is progression-free survival (PFS). To achieve 80% power to show a significant response benefit with a one-sided alpha level of 0.10, assuming a threshold progression-free survival of 3 months and an expected value of at least 5.4 months, we estimated that 32 patients are necessary. Secondary endpoints include overall survival, overall response rate, safety, and exploratory biomarker analysis for differentiating anti-VEGF drug in 2nd-line chemotherapy for unresectable or metastatic colorectal cancer. Discussion This is the first study to investigate whether FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for unresectable or metastatic colorectal cancer. Switching to a different type of anti-VEGF drug in second-line therapy after FOLFOXIRI plus bevacizumab appears to be an attractive treatment strategy when considering survival benefit. It is expected that this phase II study will prove the efficacy of this strategy and that a biomarker for drug selection will be discovered. Trial registration Japan Registry of Clinical Trials jRCTs071190003. Registered April 18, 2019.


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