Additional Line Of Therapy Research Articles

PCN33 - Real-World Costs of Increasing Complexity of Cancer Care

Treating cancer is an important health care outcome but it is costly. Increasing numbers of anti-cancer treatments are becoming available. These new treatments can be used as new additional lines of therapy - where treatments are used in succession after the failure of previous treatments. Randomised controlled trials rarely involve multiple lines of therapy. Therefore, the relationship between treatments, cost and the effectiveness require real-world data. This study estimates the cost per month for lines of therapy in the Australian health system. An analysis of the cost per month of a prospective advanced cancer Australian cohort (228 patients) was undertaken. Activity was identified from reimbursement and administrative databases and costed. Lines of therapy were estimated from medical notes. A panel of multiple observations for individuals over time was constructed. Multivariate regression was undertaken to control for confounders. Price changes were calculated to maintain the cost as estimated in the initial line of therapy. The total cost of the cohort was $AUD 19,000,000. The mean cost per month was $4,384. The cost in the first line was approximately $4,000 and increased to $8,000 per month for later lines of therapy. The results of the multivariate analysis suggested cost rose by $1,700 per month in the second line to $2,400 per month in the fifth line of therapy after adjusting for confounders. It was estimated that price reductions of 28% (95% CI 14 to 40%) would be required to return the cost per month to original levels. Real-world data is not easy to obtain, and analyses need careful adjustment for confounding. This information is required to ensure that the relationship between costs and survival is understood, appropriate policies introduced and the impacts of the policies are able to be monitored. The results of this study need to be confirmed in other cohorts.

Ten-year follow-up of pentostatin combined with cyclophosphamide, and rituximab in previously untreated indolent B-cell lymphoma.

e19040 Background: Frontline regimens for indolent lymphoma are effective, but patients still suffer from relapse. From 2005 to 2007 we enrolled previously untreated patients on a phase II trial to investigate response rate and efficacy of pentostatin combined with cyclophosphamide and rituximab (PCR). PCR is an effective frontline therapy in chronic lymphocytic leukemia. We report the final analysis with a median follow up of nearly ten years. Methods: Patients were treated with 6 cycles of therapy with additional 3 cycles in case of not attaining a CR/CRu. All patients received Pentostatin (4 mg/m2), Cyclophosphamide (600 mg/m2), and Rituximab (375 mg/m2) on day one and every 21 days. Results: Of the 83 patients, five were considered unevaluable for response, but are included as non-responders in our intent-to-treat analysis. Diagnoses included FL (43.4%), SLL (38.5%), and MZL (18.1%). 78.3% had Ann Arbor stage IV lymphoma and 63.9% had bone marrow (BM) involvement. For all 83 patients, the overall response was 92%, and most toxicity events were hematologic, with grade ≥3 neutropenia in 68 of 509 cycles of chemotherapy administered. Long term toxicity includes secondary malignancies in 14 patients. Two patients developed treatment related MDS/AML and both occurred after additional lines of therapy. PFS at 10 years for FL, MZL, and SLL was 71%, 67% and 15%, respectively. PFS was affected by clinicopathologic characteristics. 10-year PFS rates for those with pretreatment β2M < 2.2 and > 2.2 mg/l were 71 % and 21 % respectively. Patients without BM involvement had 10-year PFS of 72% versus 29% for those with BM involvement. The median OS has not been reached. The overall survival rate was 87% at 5 years and 64% at 10 years. The difference in OS rate was statistically significant based on histology, 94% for FL, 66% for MZL, and 39 % for SLL. Conclusions: Long term follow up confirms that PCR is an effective, robust and tolerable treatment regimen for indolent B-cell lymphomas with 34 of 36 patients with FL alive at 10 years with 27 remaining in remission. Clinical Trial Information NCT00496873 Clinical trial information: NCT00496873.

Clinical outcomes of adolescents and young adults (AYA) with advanced solid tumors participating in phase I trials.

10536 Background: AYA cancer patients are relatively under-represented in clinical trials, with no published data regarding their outcomes in phase I studies. Trials utilizing novel therapeutic agents are often considered in these patients, due to their tendency to have good organ reserve, and ability to tolerate additional lines of therapy. This study describes the experience of AYA patients with advanced solid tumors treated in a specialized drug development unit. Methods: Patient characteristics and clinical outcomes of AYA patients (defined as age 15 to 39 years at time of initial cancer diagnosis) treated at the Drug Development Unit, Royal Marsden Hospital, United Kingdom, between 2002 and 2016, were captured and analyzed from case and trial records. Results: From a database of 2631 patients treated on phase I trials, 219 AYA patients (8%) were identified. Major tumor types included gynaecological cancer (24%), sarcoma (18%), gastrointestinal (16%) and breast cancer (11%). Patients had a median of 3 previous lines of systemic chemotherapy (range 0 – 6), and 19% participated in 2 or more phase I studies. Twenty (9%) had a known hereditary cancer syndrome (most commonly BRCA), 27% had a family history (FH) of cancer, 15% no FH and 49% no FH documented. Molecular characterization of tumors (n = 45) identified mutations most commonly in p53 (33%) , PI3KCA (18%) and KRAS (9%) . Major trial categories included DNA damage repair (16%), PI3K (16%) and anti-angiogenesis (15%) agents. Grade 3/4 toxicities were experienced in 25% of patients (10% hematological). Of the 214 evaluable patients, objective response rate was 12%, with clinical benefit rate at 6 months of 22%. Median progression free survival was 2.3 months (95% CI: 1.9 to 2.8), median OS was 7.6 months (95% CI: 6.3 to 9.5), and 2-year OS was 11%. Of patients with responses, 35% were matched to phase I trials based on germline or somatic genetic aberrations. Conclusions: A sub-group of AYA patients with advanced solid tumors derive considerable benefit from participating in trials involving novel therapeutics. Future research must focus on predictive biomarkers and molecular profiling to identify those that would benefit from novel therapies.

Outcomes of metastatic adrenocortical carcinoma (ACC): A 16-year single institutional experience.

e16088 Background: ACC is a rare malignancy with limited data to guide management of metastatic disease. Prior research regarding survival has focused on pts with locoregional disease, but has not offered insight into the management and outcomes of pts with metastatic disease. Methods: We retrospectively reviewed patients (pts) with metastatic ACC who were treated with systemic therapy between January 2000 and October 2016 at The Ohio State University Comprehensive Cancer Center. Kaplan-Meier and Cox proportional hazards regression models were used for survival analysis. Results: A total of 18 pts received systemic therapy for distant metastatic disease. Median age at diagnosis was 51 (range 31 – 72). Median overall survival (OS) from time of diagnosis of ACC was 15.5 months (95% CI 4.8 – 28.2), and from time of systemic treatment (ST) was 7.1 months (95% CI 3.3 – 26). A germline variant of uncertain significance in MSH2 (c.138C > G) was identified in one patient. Baseline FDG-PET scans were obtained in 11/18 pts, and demonstrated avidity in all patients. Maximum SUV ranged from 4.1 to 47.6, with a median of 15. First line therapy was etoposide, doxorubicin, cisplatin, and mitotane (EDPM) in 13/18 pts and clinical trial with IMC-A12 (IGF-1 receptor antibody) in four pts. Median duration of first line therapy was 1.8 months (95% CI 0.9 – 2.8). Survival was not statistically different for patients receiving EDPM as first or second line therapy (median OS 23.3 vs 12.0 months, p = 0.96). Additional lines of therapy included EDPM, IMC-A12, AT-101, mifepristone, OSI-906 (IGF-1R inhibitor), and nivolumab. Median lines of therapy given were 2. The presence of bone metastases (p = 0.69) or lung metastases (p = 0.21) at the time of initiation of ST was not associated with OS from ST. Conclusions: In our experience, the prognosis of pts with metastatic ACC receiving systemic therapy is poor with most pts receiving ≤ 2 lines of therapy. Patients receiving first or second line EDPM seemed to have worse outcomes than noted in previously published trials, possibly due to our patients being sicker at baseline. Metastasis to the lung or bone at initiation of ST did not impact OS.

Real-World Treatment Patterns in Relapsed or Refractory Multiple Myeloma: Evidence from a Medical Chart Review in the United Kingdom

Abstract INTRODUCTION: Despite advancements in induction and maintenance therapies leading to improved response rates and overall survival (OS), virtually all patients with multiple myeloma (MM) eventually relapse. Improvement in outcomes in relapsed and/or refractory multiple myeloma (RRMM) remains an area of unmet need, yet there is a shortage of data describing typical treatment patterns in these patients in real-world practice settings. Such data may help inform future health technology assessments and other regulatory evaluations of current and new therapies in RRMM. To help address this information gap, we analyzed retrospective data from a cohort of RRMM patients in the United Kingdom (UK). METHODS: A retrospective medical record review was conducted in a cohort (n = 216) of patients with RRMM in the UK. Patients were selected (based on randomly generated first letter of last name) from the caseloads of 41 hematology/oncology providers across the UK. Specific inclusion criteria were: ≥18 years of age at initial MM diagnosis; first determined to have RRMM between January 1, 2009 and December 31, 2011, where RRMM was defined by (1) receipt of a first-line (induction) treatment regimen of chemotherapy with or without stem cell transplant (SCT) and with or without post-induction/SCT maintenance therapy and (2) disease progression while on or at any time after completion of first-line therapy. Patients were retrospectively assessed on second- and third-line treatment regimens received, treatment duration, and reasons for treatment discontinuation from date of first relapse or progression (study index date). All analyses were descriptive and exploratory in nature. RESULTS: Demographic and clinical characteristics of the study sample are presented in Table 1. Mean (SD) age at study index (first relapse, or RRMM diagnosis) was 65.6 (8.7) years, with approximately half of patients (53%) having advanced age (≥65 years). The study sample was 62.5% male and more than two-thirds of patients (69%) were still alive at the time of the medical record review. Among the 216 patients studied, 208 (97%) received ≥1 additional line of systemic chemotherapy after first relapse (Table 2); 94 patients (43%) received ≥2 additional lines of therapy (i.e., at least second- and third-line therapy) during the observation period. The most common second-line regimen was bortezomib + dexamethasone with or without other agents (66% of second-line initiators), followed by lenalidomide + dexamethasone with or without other agents (20%). Median duration of second-line treatment was 6 cycles over a median of 5.4 months. Among the 98% of patients who discontinued second-line treatment, a majority (62%) stopped therapy due to reaching complete response with no additional benefit expected; 33 patients (16%) discontinued second-line treatment due to disease progression and 8% discontinued due to toxicities. Lenalidomide + dexamethasone with or without other agents was the predominant third-line regimen (67% of third-line initiators); bortezomib + dexamethasone with or without other agents was the next most common third-line regimen (14%). Among the 94 patients receiving third-line treatment, median duration was 6 cycles over a median of 5.7 months. The leading reason for third-line discontinuation was disease progression (48%); 30% of patients discontinued because they reached complete response with no anticipated additional benefit, and 20% discontinued because of loss or lack of response to therapy. CONCLUSIONS: In the RRMM cohort reviewed here, bortezomib-containing regimens were the predominant second-line therapy and lenalidomide + dexamethasone was the most common third-line regimen. The most common reasons for discontinuation of RRMM treatments were disease progression and physician-judged achievement of complete response with no additional benefit expected. While the most common reason for therapy discontinuation in second-line treatment was reaching complete response with no additional benefit expected, in third-line therapy it was disease progression. With growing evidence in the RRMM literature that treatment to progression may be superior to a fixed duration of therapy, as well as evidence of premature discontinuation being associated with inferior outcomes, the relatively short second-line duration reported here ( Download : Download high-res image (280KB) Download : Download full-size image Download : Download high-res image (383KB) Download : Download full-size image Disclosures Lin: Takeda: Employment. Davis: Takeda: Research Funding. Kaye: Takeda: Research Funding. Luptakova: Takeda Oncology: Employment. Nagar: Takeda: Research Funding. Seal: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership.

Real-World Treatment Patterns in Relapsed or Refractory Multiple Myeloma: Evidence from a Cohort Review in the United Kingdom

INTRODUCTION: Despite advancements in induction and maintenance therapies leading to improved response rates and overall survival (OS), virtually all patients with multiple myeloma (MM) eventually relapse. Improvement in outcomes in relapsed and/or refractory multiple myeloma (RRMM) remains an area of unmet need, yet there is a shortage of data describing typical treatment patterns in these patients in real-world practice settings. Such data may help inform future health technology assessments and other regulatory evaluations of current and new therapies in RRMM. To help address this information gap, we analyzed retrospective data from a cohort of RRMM patients in the United Kingdom (UK).METHODS: A retrospective medical record review was conducted in a cohort (n = 216) of patients with RRMM in the UK. Patients were selected (based on randomly generated first letter of last name) from the caseloads of 41 hematology/oncology providers across the UK. Specific inclusion criteria were: ≥18 years of age at initial MM diagnosis; first determined to have RRMM between January 1, 2009 and December 31, 2011, where RRMM was defined by (1) receipt of a first-line (induction) treatment regimen of chemotherapy with or without stem cell transplant (SCT) and with or without post-induction/SCT maintenance therapy and (2) disease progression while on or at any time after completion of first-line therapy. Patients were retrospectively assessed on second- and third-line treatment regimens received, treatment duration, and reasons for treatment discontinuation from date of first relapse or progression (study index date). All analyses were descriptive and exploratory in nature.RESULTS: Demographic and clinical characteristics of the study sample are presented in Table 1. Mean (SD) age at study index (first relapse, or RRMM diagnosis) was 65.6 (8.7) years, with approximately half of patients (53%) having advanced age (≥65 years). The study sample was 62.5% male and more than two-thirds of patients (69%) were still alive at the time of the medical record review. Among the 216 patients studied, 208 (97%) received ≥1 additional line of systemic chemotherapy after first relapse (Table 2); 94 patients (43%) received ≥2 additional lines of therapy (i.e., at least second- and third-line therapy) during the observation period. The most common second-line regimen was bortezomib + dexamethasone with or without other agents (66% of second-line initiators), followed by lenalidomide + dexamethasone with or without other agents (20%). Median duration of second-line treatment was 6 cycles over a median of 5.4 months. Among the 98% of patients who discontinued second-line treatment, a majority (62%) stopped therapy due to reaching complete response with no additional benefit expected; 33 patients (16%) discontinued second-line treatment due to disease progression and 8% discontinued due to toxicities. Lenalidomide + dexamethasone with or without other agents was the predominant third-line regimen (67% of third-line initiators); bortezomib + dexamethasone with or without other agents was the next most common third-line regimen (14%). Among the 94 patients receiving third-line treatment, median duration was 6 cycles over a median of 5.7 months. The leading reason for third-line discontinuation was disease progression (48%); 30% of patients discontinued because they reached complete response with no anticipated additional benefit, and 20% discontinued because of loss or lack of response to therapy.CONCLUSIONS: In the RRMM cohort reviewed here, bortezomib-containing regimens were the predominant second-line therapy and lenalidomide + dexamethasone was the most common third-line regimen. The most common reasons for discontinuation of RRMM treatments were disease progression and physician-judged achievement of complete response with no additional benefit expected. While the most common reason for therapy discontinuation in second-line treatment was reaching complete response with no additional benefit expected, in third-line therapy it was disease progression. With growing evidence in the RRMM literature that treatment to progression may be superior to a fixed duration of therapy, as well as evidence of premature discontinuation being associated with inferior outcomes, the relatively short second-line duration reported here (<6 months) further highlights a potential unmet need in this disease area. [Display omitted] [Display omitted] DisclosuresLin:Takeda: Employment. Davis:Takeda: Research Funding. Kaye:Takeda: Research Funding. Luptakova:Takeda Oncology: Employment. Nagar:Takeda: Research Funding. Seal:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership.

Prolonged Progression-Free Survival Is Possible in Patients with Diffuse Large B-Cell Lymphoma Receiving > 1 Salvage Therapies before Autologous Stem Cell Transplant

IntroductionWhile 50-60% of patients with diffuse large B-cell lymphoma (DLBCL) are cured with initial chemoimmunotherapy such as R-CHOP, many patients will relapse and require additional therapy. Historically, autologous stem cell transplant (ASCT) has been utilized in chemo-sensitive patients with relapsed DLBCL although the role of ASCT in patients who require > 1 salvage treatment to achieve remission is less defined due to concerns about the likelihood of long-term remission in that population. We evaluated the outcome of ASCT in patients who required >1 salvage therapy.MethodsWe included all patients undergoing ASCT for relapsed/refractory DLBCL at our site between 2005-2016 who received > 1 salvage treatment before transplant, with radiation therapy considered a salvage treatment if given after relapse but before ASCT. We collected demographic, clinical, laboratory and pathologic data on all patients. We defined progression-free survival (PFS) as time from ASCT to date of progression or death from any cause and overall survival (OS) as time from ASCT to date of death from any cause. Living patients were censored at the time of their last follow up. Univariate Cox proportional hazards models of PFS and OS were fit and Kaplan-Meier plots were developed to estimate the impact of variables of interest on survival.ResultsOut of 259 patients undergoing ASCT for DLBCL, 43 received > 1 salvage treatment, the median age was 51 years and 23 patients were male. Twenty patients had stage III/IV disease at diagnosis. The median time to relapse from the time of diagnosis was 9.3 months, and 42% of patients experienced a relapse > 12 months after diagnosis. Twenty-six patients (60%) received radiation as one of their salvage therapies, 25 patients (58%) received R-ICE as their first salvage therapy and 10 (23%) patients received R-ICE as their second salvage treatment. All patients received either 2 (n=39) or 3 (n=4) salvage therapies before ASCT, and the response to the initial salvage therapy received was CR in 4 patients, PR in 14 patients, SD in 1 patient, and PD in 14 patients, with initial response to salvage therapy missing in 10 patients. The median PFS for all patients was 15.9 months and the median OS was 57.2 months (Figure 1a). Receipt of radiation and having disease sensitive to treatment at the time of ASCT were the only factors associated with prolonged PFS and OS. Median PFS has not been achieved in patients who received radiation while patients who did not receive radiation had a median PFS of 4.2 months (HR = 0.36, p = 0.014; Figure 1b). Patients who had a chemo sensitive disease status at transplant had a median PFS of 22.6 months; however, patients with refractory disease at transplant only achieved a median PFS of 3.6 months (HR = 0.30, p=0.008). Remaining factors including conditioning regimen, time to relapse, and number of salvage therapies were not significantly associated with PFS or OS.ConclusionsASCT can result in prolonged PFS/OS in patients requiring > 1 salvage therapy especially in the case of sensitive disease. Radiation as an additional line of therapy is associated with improved PFS/OS, suggesting this can be included to induce remission in patients who fail to achieve CR with initial salvage treatment. While uncommon, patients with chemo-refractory disease can also have durable survival and should not be excluded from transplant. [Display omitted] [Display omitted] DisclosuresCalzada:Seattle Genetics: Research Funding. Flowers:Spectrum, Janssen, Infinity, AbbVie, Acerta, Pharmacyclics, TG Therapeutics: Research Funding; Celgene Corporation: Consultancy, Honoraria; Optum Rx, Seattle Genetics, Genentech/Roche: Consultancy; Gilead: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Seattle Genetics: Research Funding. Cohen:Bristol-Myers Squibb: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium/Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Multiple myeloma: patient outcomes in real-world practice.

SummaryWith increasing number of therapies available for the treatment of multiple myeloma, it is timely to examine the course of patients' journeys. We investigated patient characteristics, treatment durations and outcomes, and symptom burden across the treatment pathway in Belgium, France, Germany, Italy, Spain, Switzerland and the UK. In total, 435 physicians retrospectively reviewed 4997 patient charts. Profiles of patients diagnosed with multiple myeloma during the last 12 months were similar across countries; bone pain was the most common presentation. Median duration of first‐line therapy was 6 months, followed by a median treatment‐free interval of 10 months; both these decreased with increasing lines of therapy, as did time to progression. Depth of response, as assessed by the treating physician, also decreased with each additional line of therapy: 74% of patients achieved at least a very good partial response at first line, compared with only 11% at fifth line. Deeper responses were associated with longer time to progression, although these were physician‐judged. Toxicities and co‐morbidities increased with later treatment lines, and were more likely to have led to discontinuation of treatment. These real‐world data provide an insight into patient outcomes and treatment decisions being made in clinical practice.

Abstract 3588: Emergence of multiple EGFR extracellular mutations during cetuximab treatment in colorectal cancer

Abstract Colorectal cancer (CRC) patients who respond to the anti-EGFR antibody cetuximab often develop resistance within several months of initiating therapy. To design new lines of treatment the molecular landscape of resistant tumors must be ascertained. We investigated the role of mutations in the EGFR signalling axis on the acquisition of resistance to cetuximab in patients and cellular models. Mutational profiling was performed on both biopsies collected from 37 CRC patients who became refractory to cetuximab and on a collection of cetuximab-resistant derivatives obtained from CRC cells sensitive to EGFR blockade. The genetic profile of tumor specimens obtained after cetuximab treatment revealed the emergence of a complex pattern of mutations in EGFR, KRAS, NRAS, BRAF and PIK3CA genes, including two novel EGFR ectodomain mutations. Mutational profiling of cetuximab resistant cells recapitulated the molecular landscape observed in clinical samples and revealed three additional EGFR ectodomain alleles. Structural modelling showed that these mutations are located in the cetuximab-binding region, except for one mutant. Functionally, EGFR ectodomain mutations prevent binding to cetuximab but a subset is permissive for interaction with panitumumab. In conclusion, we reported that colorectal tumors evade EGFR blockade by constitutive activation of downstream signalling effectors and through mutations affecting receptor-antibody binding. Both mechanisms of resistance may occur concomitantly. Our data have implications for designing additional lines of therapy for CRC patients who relapse upon treatment with anti-EGFR antibodies. Citation Format: Luca Lazzari, Sabrina Arena, Beatriz Bellosillo, Giulia Siravegna, Alejandro Martínez, Israel Cañadas, Noelia Ferruz, Mariangela Russo, Sandra Misale, Iria González, Mar Iglesias, Elena Gavilan, Giorgio Corti, Sebastijan Hobor, Giovanni Crisafulli, Marta Salido, Juan Sánchez, Alba Dalmases, Joaquim Bellmunt, Gianni De Fabritiis, Ana Rovira, Federica Di Nicolantonio, Joan Albanell, Alberto Bardelli, Clara Montagut. Emergence of multiple EGFR extracellular mutations during cetuximab treatment in colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3588. doi:10.1158/1538-7445.AM2015-3588

Treatment patterns and cost for colorectal cancer by line of therapy and metastasis status.

e14658 Background: Patterns and cost of care are thought to vary substantially as patients with colorectal cancer (CRC) progress from first to third line therapy and in the presence of metastatic disease. Our aim was to compare patterns and cost of care in these patients. Methods: A retrospective analysis was performed using claims from the Optum Oncology Research Database. Patients 18 years and older, diagnosed with CRC and received chemotherapy or biologic therapy between Jul 1, 2004 and Dec 31, 2010, who were insured by a commercial health plan were included. Chemotherapy combinations were assessed in patients receiving first, second and third line of therapy for CRC; and for patients with/without metastatic disease. Inpatient, outpatient, chemotherapy, biologic-related, and total median annual costs were compared by the Kruskal-Wallis test. Results: 1039 patients were included. FOLFOX and fluorouracil monotherapy were the most common first-line therapies, each accounting for approximately 27% of patients who received any chemotherapy. Oxaliplatin-based regimens were the most common second-line therapy (45% of patients). Irinotecan-based regimens were the most common third line therapy (35% of patients). Biologic therapy was much more common in patients with metastases (39% vs. 5%; p&lt;0.0001) and in patients receiving third line therapy (65% vs. 8%, p&lt;0.0001). The total cost of care increased significantly for patients receiving first ($25,782), second ($36,951), and third ($86,944) line therapy (p&lt;0.0001 for all pairwise comparisons). Costs were significantly greater (p&lt;0.0001) for patients receiving third versus first line therapy for outpatient care ($39,952 vs. $15,521), inpatient care ($3,668 vs. $1,721), chemotherapy ($14,059 vs. $3,662) and biologic therapy ($28,824 vs. $4,899). Total costs were significantly greater for patients with metastases ($39,001) compared with those without ($8,989; p&lt;0.0001). Conclusions: Treatment patterns vary significantly by line of therapy in patients with CRC. The total cost of care increased significantly as patients received additional lines of therapy and for patients with metastases. Biologics appear to be the most significant driver of these increased costs.

Metastatic Colon Cancer, Version 3.2013

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, patient surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Colon Cancer Panel meets annually to review comments from reviewers within their institutions and to reevaluate and update their recommendations. In addition, the panel has interim conferences as new data necessitate. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel's discussions surrounding metastatic colorectal cancer for the 2013 update of the guidelines. Importantly, changes were made to the continuum of care for patients with advanced or metastatic disease, including new drugs and an additional line of therapy.

Tandem Autologous Hematopoietic Progenitor Cell Transplantation (AHPCT) for High-Risk Hodgkin Lymphoma: Mature Results of a Prospective Trial

Abstract 1990▪▪This icon denotes a clinically relevant abstractThe efficacy of high-dose chemotherapy (HDC) and AHPCT is inferior for Hodgkin lymphoma patients (pts) with high-risk features, commonly defined as primary induction failure (PIF) or early relapse (within 1 year of achieving remission). Phase II studies have suggested that tandem courses of HDC with AHPCT may improve transplant outcomes. We therefore evaluated this approach in a single-center, prospective, phase II study. The primary endpoint of the trial was relapse-free survival (RFS). The intention-to-treat (ITT) analysis included 42 subjects with PIF or early relapse (within 1 year) who signed consent, of whom 37 underwent both transplants in 2002–2010 (3 were denied insurance coverage for tandem AHPCT, 1 had inadequate HPC harvest, and 1 withdrew). These subjects were compared retrospectively with 96 control pts who met eligibility criteria for the trial and underwent a single AHPCT from 1995–2009. HPC mobilization was with etoposide/filgrastim in all tandem AHPCT subjects, and in 55% of controls. Tandem pts received melphalan 150 mg/m2 with AHPCT. After a median of 52 days, tandem pts then received CBV (N=30) or busulfan, etoposide, and cyclophosphamide (BuCyVP; N=7, due to carmustine shortage) with AHPCT. Controls received BuCyVP (N=95) or CBV (N=1) with AHPCT. There were no clinically significant baseline differences between the tandem and control groups.With a median 54 months follow-up at the time of analysis among tandem AHPCT survivors, 23 tandem pts and 47 controls were alive at the time of analysis. Causes of death among tandem AHPCT recipients included relapse (N=13), pulmonary (N=1), secondary malignancy (N=3), other (N=2). For controls, causes of death included relapse (N=37), pulmonary (N=2), secondary malignancy (N=2), other (N=8). Among tandem pts who received both transplants, 100-day mortality did not occur; there were 7 deaths within 100 days post AHPCT among controls (P=0.09). Median RFS was 15.5 months for tandem pts and 26.3 months for controls (P=0.28). Median overall survival (OS) was 54.9 months for tandem pts vs. 73.1 months for controls (P=0.76). [Display omitted] In multivariable analysis, factors associated with survival included race (non-Caucasian vs. Caucasian, HR 2.68, 95% CI 1.30–5.54, P=0.008), extent of prior chemotherapy (per 1 regimen increase, HR 2.54, 95% CI 1.71–3.77, P<0.001), and disease bulk (>10 cm vs. < 10 cm, HR 2.76, 95% CI 1.57–4.84, P<0.001). For RFS, prognostic factors included extent of prior chemotherapy (HR 2.15, 95% CI 1.47–3.13, P<0.001), disease bulk (HR 1.89, 95% CI 1.14–3.15, P=0.014), and disease status at transplant (relapsed/refractory vs. CR/PR, HR 1.91, 95% CI 1.14–3.20, P=0.014).In conclusion, tandem AHPCT provides no demonstrable advantage over a single course of HDC with AHPCT in our analysis. More effective treatments are needed for pts with high-risk Hodgkin lymphoma, particularly ethnic minorities or those with bulky disease at transplant. Transplant outcomes suffered with additional lines of therapy before AHPCT, as shown in other published studies; thus, AHPCT should be prioritized over other interventions whenever feasible, at the time of induction failure or first relapse. Disclosures:No relevant conflicts of interest to declare.

Efficacy of rituximab in primary immune thrombocytopenia: an analysis of adult pretreated patients from everyday hematological practice

Although rituximab has seen increasing use in the treatment of immune thrombocytopenia (ITP) for many years, its therapeutic role in this disease remains unclear. We retrospectively analyzed data of all patients with ITP treated with rituximab (375 mg/m(2) once weekly for four consecutive weeks) and consecutively entered the findings into the databases of six large academic centers in the Czech Republic. A total of 114 patients were included in the analysis. All of the patients received rituximab as a second or additional line of therapy. The overall response rate (ORR) after rituximab therapy was 72 % [48 % complete response (CR), 24 % partial response (PR)] at month 6, and 69 % (45 % CR, 24 % PR) at month 12. For the group of patients with newly diagnosed (acute) ITP, the results of treatment were significantly better than for the group of patients with persistent or chronic ITP; nonetheless, this group of patients was far too small (n = 18) for our findings to be generalized. Multivariate analysis revealed that the ORR was significantly influenced primarily by the number of therapies prior to rituximab (the more previous therapies, the worse treatment response). The results of our analysis "from everyday hematological practice" confirm the high efficiency of rituximab treatment in pretreated adult patients with ITP.

An additional line of therapy with pegylated interferon and ribavirin after rituximab in a patient with hepatitis C virus-related mixed cryoglobulinaemia and indolent non-Hodgkin's lymphoma previously treated with interferon.

It is known that hepatitis C virus (HCV) infection is involved in development of indolent lymphomas due to chronic antigenic stimulation of B-cell lymphocytes1. The type II mixed cryoglobulinaemia syndrome is characterised by the production of monoclonal antibodies of the IgM type with rheumatoid factor activity. The typical clinical features of this disease are purpura, vasculitis of small and medium vessels, arthralgia, asthenia and renal and neurological involvement. Many patients affected by HCV and mixed cryoglobulinaemia (MC-HCV) also have a clonal B-cell expansion1. In the last few years, the therapeutic approach to MC-HCV has changed radically as a result of the introduction of rituximab in combination with ribavirin and pegylated interferon2–4. Here we report the case of a patient with MC-HCV-related vasculitis and indolent non-Hodgkin’s lymphoma (NHL), previously treated with interferon, who then received therapy with anti-CD20 monoclonal antibody (rituximab), pegylated-interferon and ribavirin in sequence. The 20-year follow-up of this patient from the initial onset of disease is described.

Gefitinib: a consideration of cost

Cancer care is one of the most significant healthcare costs in the USA. The National Institute of Health (NIH) estimates healthcare spending at US$171.6 billion (2002), with lung cancer estimated as the diagnosis with the second highest cost. As additional lines of therapy and newer targeted agents are incorporated into the treatment of lung cancer, these costs will further increase. Gefitinib, an EGF receptor tyrosine kinase inhibitor, is well established in Asia for the treatment of advanced non-small-cell lung cancer. Although not widely available in the West, encouraging data have recently been reported from a large, global Phase III study of gefitinib in advanced non-small-cell lung cancer. This paper reviews the data supporting the use of gefitinib in the treatment of advanced non-small-cell-lung cancer and considers its potential economic impact, as well as quality-of-life outcomes, compared with cytotoxic chemotherapy.

Cytotoxic chemotherapy for advanced, non-resectable colorectal cancer

The past decade has seen a step-change in the treatment of advanced, inoperable colorectal cancer. The choice of fluoropyrimidine extends beyond 5-FU to orally available analogues, which have been shown to be equivalent in activity to intravenous 5-FU. The emergence of two additional active chemotherapy agents, irinotecan and oxaliplatin, has improved prognosis of these patients by providing additional lines of therapy. However, this has resulted in an increasing number of regimens, combinations and sequences available to clinicians and patients. In this review we summarise the evidence supporting the use of all active chemotherapy agents, as appropriate, to improve the survival of patients with mCRC, with particular attention to mature phase III trials. The role of novel biological therapies is reviewed elsewhere and will not be covered. Ultimately, the choice of regimen and sequence will depend on patient-specific factors, patient and clinician choice, volume of disease, aims of therapy and, in time, biological markers which may predict for response to a particular drug of combination.