Determinants of first-line treatment selection in advanced pancreatic ductal adenocarcinoma (PDAC).

468 Background: Chemotherapy options currently available for the first-line treatment of advanced PDAC include FOLFIRINOX (FX), gemcitabine with nab-paclitaxel (GP) and single agent gemcitabine (Gem). GP was introduced most recently and funded for clinical use in British Columbia (BC) in September 2014. In this retrospective analysis, we explore the impact of GP availability on first-line treatment selection and overall survival (OS) in advanced PDAC. Methods: The BC Cancer Agency provincial pharmacy database was used to identify patients (pts) who started FX, GP or Gem between January and August 2014 (pre-GP) or January and August 2015 (post-GP). Pts were eligible for inclusion if they received at least one cycle of first-line therapy for locally advanced or metastatic PDAC. Clinical data were extracted from electronic medical records. OS was defined as time from diagnosis of advanced PDAC to death and compared by treatment era, adjusting for age, ECOG, comorbidities, disease extent and baseline CA19-9. Results: 286 pts fulfilled eligibility criteria: 88 (31%) with locally advanced and 198 (69%) with metastatic disease. 131 and 155 pts were treated in the pre- and post-GP eras respectively. Prior to GP approval, 44% and 49% of pts received Gem and FX; this decreased to 21% and 33% after GP funding, with 46% of pts receiving GP in the latter period. Nine (7%) pts received GP in the pre-GP era, either through self-pay or addition of nab-paclitaxel after approval. There were no significant differences in pt characteristics across both eras. 46% of pts who received GP post approval had ECOG ≥ 2. The proportion of pts receiving second-line therapy was lower in the post-GP era (22% vs. 38%). Median OS in the post-GP era was 8.1 vs. 10.1 months in the pre-GP era; adjusted HR 1.28 (95% CI 0.96–1.71). Pts with ECOG ≥ 2 who received GP had a median OS of 6.5 months. Conclusions: After GP was funded, it became the preferred first-line regimen for advanced PDAC. Its more frequent use instead of FX did not appear to compromise overall survival even though a substantial proportion of pts were ECOG ≥ 2 and few pts received second-line therapy.

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Lenvatinib as the key component of first-line therapy for patients with unresectable hepatocellular carcinoma

Modern Oncology ◽

10.26442/18151434.2020.3.200353 ◽

2020 ◽

Vol 22 (3) ◽

pp. 142-148

Author(s):

L. V. Bolotina

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy ◽

Unresectable Hepatocellular Carcinoma ◽

First Line Treatment

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.

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Persistent Head and Neck Cancer Following First-Line Treatment

Cancers ◽

10.3390/cancers10110421 ◽

2018 ◽

Vol 10 (11) ◽

pp. 421 ◽

Cited By ~ 4

Author(s):

Teresa Steinbichler ◽

Madeleine Lichtenecker ◽

Maria Anegg ◽

Daniel Dejaco ◽

Barbara Kofler ◽

...

Keyword(s):

Overall Survival ◽

Head And Neck Cancer ◽

Median Overall Survival ◽

Complete Response ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Persistent Disease ◽

Line Therapy ◽

First Line Treatment

Background: Following first-line treatment of head and neck cancer (HNC), persistent disease may require second-line treatment. Methods: All patients with HNC treated between 2008 and 2016 were included. Second-line treatment modalities and survival of patients were analyzed. Results: After first-line therapy, 175/741 patients had persistent disease. Of these, 112 were considered eligible for second-line treatment. Second-line treatment resulted in 50% complete response. Median overall survival of patients receiving second-line therapy was 24 (95% CI: 19 to 29) months; otherwise survival was 10 (9 to 11; p < 0.0001) months. Patients receiving second-line surgery had a median overall survival of 45 (28 to 62) months, patients receiving second-line radiotherapy had a median overall survival of 37 (0 to 79; p = 0.17) months, and patients receiving systemic therapy had a median overall survival of 13 (10 to 16; p < 0.001) months. Patients with persistent HNC in the neck had a better median survival (45 months; 16 to 74 months; p = 0.001) than patients with persistence at other sites. Conclusion: Early treatment response evaluation allows early initiation of second-line treatment and offers selected patients with persistent disease a realistic chance to achieve complete response after all. If possible, surgery or radiotherapy are preferable.

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Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline

Journal of Clinical Oncology ◽

10.1200/jco.20.02672 ◽

2020 ◽

Vol 38 (36) ◽

pp. 4317-4345 ◽

Cited By ~ 1

Author(s):

John D. Gordan ◽

Erin B. Kennedy ◽

Ghassan K. Abou-Alfa ◽

Muhammad Shaalan Beg ◽

Steven T. Brower ◽

...

Keyword(s):

Phase Iii ◽

Advanced Hepatocellular Carcinoma ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Advanced Hcc ◽

First Line Therapy ◽

Line Therapy ◽

First Line Treatment

PURPOSE To develop an evidence-based clinical practice guideline to assist in clinical decision making for patients with advanced hepatocellular carcinoma (HCC). METHODS ASCO convened an Expert Panel to conduct a systematic review of published phase III randomized controlled trials (2007-2020) on systemic therapy for advanced HCC and provide recommended care options for this patient population. RESULTS Nine phase III randomized controlled trials met the inclusion criteria. RECOMMENDATIONS Atezolizumab + bevacizumab (atezo + bev) may be offered as first-line treatment of most patients with advanced HCC, Child-Pugh class A liver disease, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1, and following management of esophageal varices, when present, according to institutional guidelines. Where there are contraindications to atezolizumab and/or bevacizumab, tyrosine kinase inhibitors sorafenib or lenvatinib may be offered as first-line treatment of patients with advanced HCC, Child-Pugh class A liver disease, and ECOG PS 0-1. Following first-line treatment with atezo + bev, and until better data are available, second-line therapy with a tyrosine kinase inhibitor may be recommended for appropriate candidates. Following first-line therapy with sorafenib or lenvatinib, second-line therapy options for appropriate candidates include cabozantinib, regorafenib for patients who previously tolerated sorafenib, or ramucirumab (for patients with α-fetoprotein ≥ 400 ng/mL), or atezo + bev where patients did not have access to this option as first-line therapy. Pembrolizumab or nivolumab are also reasonable options for appropriate patients following sorafenib or lenvatinib. Consideration of nivolumab + ipilimumab as an option for second-line therapy and third-line therapy is discussed. Further guidance on choosing between therapy options is included within the guideline. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

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MYD88 (L265P) Mutation Confers Very Poor Response and Outcome after Second-Line Therapy in Patients with Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽

10.1182/blood.v124.21.1690.1690 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1690-1690 ◽

Cited By ~ 1

Author(s):

Antonio Salar ◽

Francesc Garcia-Pallarols ◽

Concepcion Fernández-Rodríguez ◽

Blanca Sánchez-González ◽

Mari Carmen Vela ◽

...

Keyword(s):

B Cell ◽

Poor Response ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Line Therapy ◽

Myd88 L265p Mutation ◽

Myd88 L265p ◽

First Line Treatment

Abstract BACKGROUND Somatic mutations in the myeloid differentiation primary response gene 88 (MYD88) have been described in B-cell lymphomas, including DLBCL. Our group has confirmed the remarkable site-specific occurrence of MYD88 mutations at some immune-privileged locations and, in addition, has described that DLBCL patients are at high risk of progression and death after first-line treatment, with independence of other well-known clinical prognostic factors (Leukemia 2014). AIMS To further analyze the clinical responsiveness and outcome after second-line treatment in DLBCL patients carrying MYD88 L265P. METHODS A series of 175 patients with DLBCL diagnosed at our institution between 2000 and 2013 were included. Inclusion criteria were: full clinical data available, treatment with remission intention, enough material for DNA extraction and absence of HIV infection. The presence of MYD88 L265P mutation was assessed by allele-specific oligonucleotides (ASO)-PCR in DNA samples extracted from FFPE tissue. RESULTS In 129 patients (74%) treatment consisted on rituximab plus CHOP or CHOP-like schedules, while the remaining cases received other treatments depending on their clinical requirements. With a median follow-up time of 57 months, progression free survival (PFS) at 5 years after first-line treatment was 57%. Twelve of these patients (9.3%) had MYD88 L265P mutation, and these patients had a significantly worse PFS that patients who did not (18% vs 59%, p=0.018). Overall survival (OS) at 5 years after first line treatment was 65% (17% vs 72%, with vs without MYD88 mutation, respectively; p=0.001). We further analyzed the outcome after second-line treatment in 32 cases: 6 patients had refractory disease (0 with MYD88 mutation) and 26 patients were in first relapse. Three out of 5 patients carrying MYD88 mutation and 25 out of 27 patients without MYD88 mutation were treated with chemotherapy. Only one out of 5 cases (20%) with MYD88 mutation responded to second-line therapy whereas response was observed in 16 out of 27 cases (59%) without MYD88 mutation(p=0.106). PFS at 4 years from starting second-line therapy was 0 % in cases with MYD88 DLBCL and 34% in those without MYD88 mutation (p=0.092). Moreover, OS at 4 years from starting second-line therapy was 0 % in cases with MYD88 DLBCL and 37% in those without MYD88 mutation (p=0.019)(Figure 1). CONCLUSION Our study shows that MYD88 L265P in DLBCL patients is not only associated to worse respond after first -line therapy, but also to a very poor response to second-line therapy, and consequently to a dismal outcome. New treatments are urgently needed for these patients. Acknowledgments: This study was supported in part by 2014SGR567 Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Comparison Between Lymphoglobuline- and Thymoglobuline-Based Immunosuppressive Therapy as First-Line Treatment for Patients with Aplastic Anemia.

Blood ◽

10.1182/blood.v114.22.3194.3194 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3194-3194 ◽

Cited By ~ 12

Author(s):

Carlos Vallejo ◽

Pau Montesinos ◽

Ana Rosell ◽

Salut Brunet ◽

Raul Córdoba ◽

...

Keyword(s):

Hemoglobin Level ◽

Study Group ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Therapeutic Protocol ◽

Line Therapy ◽

Spanish Study ◽

First Line Treatment

Abstract Abstract 3194 Poster Board III-131 Background Immunosuppressive therapy (IST) is considered to be the first-line treatment in patients with severe aplastic anemia (AA) who are not eligible for hematopoietic stem cell transplantation (HSCT). Most IST schemes are based on the combination of anti-thymocyte globulin (ATG) plus cyclosporine A (CsA). Differently from other countries, two ATGs have been approved in Spain for AA from 2003 to 2007: Lymphoglobuline (LG) (raised in the sera of horses) and Thymoglobuline (TG) (produced in rabbits). So, during this period of time, the standard therapeutic protocol of the Spanish study group for AA included both options, and the physicians chose LG or TG based on their own wishes. Most published studies in AA are with LG, which is no longer manufactured. Recent limited data have confirmed therapeutic efficacy of TG, but no randomized studies have been performed comparing both products' activity. The aim of this report is to communicate the outcomes of a group of patients with AA who received either a LG- or TG-based scheme as first-line treatment. Patients and methods we retrospectively investigated the outcome of 110 patients with AA treated with IST at front line between 2003 and 2008. Thirty-five patients (32%) got LG (15 mg/kg/day/x5 days), and 75 patients (68%) got TG (2.5 mg/kg/day/x5 days). All patients also received methylprednisolone and CsA. Response rate (RR) was assessed at post-IST day +90, day +180, and day +365. If complete response (CR) was not reached, patients received a second course of IST, a second-line therapy (HSCT or androgens), or no treatment. When a second course of IST was employed, it included LG at the same dose as in the first course (15 mg/kg/day/x5 days), or TG at a higher dose (3.5 mg/kg/day/x5 days). CR was defined as a neutrophil count >1.5×109/L, a platelet count >100 ×109/L, and a hemoglobin level >120 g/L. Partial response (PR) was defined as a neutrophil count >0.5×109/L, a platelet count >20 ×109/L, and a hemoglobin level >80 g/L. Subgroup analyses were conducted and differences in response were tested using the chi-square statistic test. Results After the first course of IST, CR was achieved in 31 patients (28%) (group A), and PR in 20 patients (18%). Overall response (OR) was similar for both globulins (LG: 49%, TG: 45%). Thirty-five of the patients who did not reach CR after the first IST course, received a second course of IST (6 with LG and 29 with TG) (group B), and 44 patients underwent a different approach (second-line therapy or no treatment) (group C). After the second course of IST, 14 patients achieved CR (40%) and 11 patients PR (31%). OR was similar for LG (67%) and TG (72%). If we exclude patients in group C, the RR among the remaining 66 patients (who underwent 1 or 2 courses of IST) was 85% (68% CR, and 17% PR). No major drug-related toxicities were reported in the whole group of patients. Conclusions ATG-based schemes with both LG and TG were well tolerated as treatment of patients with AA. OR after first course of IST was similar in the LG and in the TG group (49% versus 45%). RR after second course of IST was also similar when LG and TG were employed (67% versus 72%). After excluding those patients who, not having reached CR after the first course, underwent an approach different from a second course of IST, RR to IST was 85%, with 68% of CR. No statistical differences were found based on the type of ATG administered. The results of this study show that TG is, at least, as effective as LG for the treatment of AA patients. Based on these and other recently published data, the current standard therapeutic protocol of the Spanish study group for AA includes TG at the dose of 3.75 mg/kg/day/x5 days for both the first and, if necessary, second course of IST. To our knowledge, no reports are available in the medical literature comparing the outcome of patients with AA who received LG or TG as the first-line therapy for AA. So, in spite of the fact that our study is retrospective and not randomized, we think our data are unique and very useful for helping physicians in switching from LG to TG. Disclosures No relevant conflicts of interest to declare.

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Patterns Of Care, Survival, and Costs Of Second-Line Treatment In Medicare Beneficiaries With Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽

10.1182/blood.v122.21.2936.2936 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2936-2936

Author(s):

Mark Danese ◽

Robert Griffiths ◽

Michelle Gleeson ◽

Tapashi Dalvi ◽

Jingyi Li ◽

...

Keyword(s):

Overall Survival ◽

Research Funding ◽

Patterns Of Care ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy ◽

Significant Factors

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.

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Activity of Idelalisib in High-Risk Follicular Lymphoma with Early Relapse Following Front Line Immunochemotherapy

Blood ◽

10.1182/blood.v126.23.2744.2744 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2744-2744 ◽

Cited By ~ 6

Author(s):

Ajay K Gopal ◽

Brad S Kahl ◽

Christopher Flowers ◽

Peter Martin ◽

Brian K Link ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

Research Funding ◽

Progression Free Survival ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Free Survival ◽

Line Therapy ◽

First Line Treatment

Abstract Background: Follicular lymphoma (FL) is the most common indolent NHL with a heterogenous natural history of disease and a median survival of 8 to 12 y, albeit ranging between 1 to 20 y. Casulo et al. (2015) identified a high-risk FL cohort of patients with progression of disease (POD) at ≤24 months following initiation of immunochemotherapy with R-CHOP. Idelalisib (Zydelig) is a first-in-class, highly selective, oral inhibitor of PI3Kd which is indicated for relapsed FL or SLL following receipt of at least two lines of systemic chemotherapy. Retrospective subgroup analysis of the idelalisib registrational trial NCT01282424 (101-09) of a cohort with early POD following immunochemotherapy was performed to assess possible activity of idelalisib in this population. Methods: A subset of 46 patients enrolled in study 101-09 were identified as having been diagnosed with FL and having received first-line immunochemotherapy, of which 37 experienced early POD, defined as starting second-line treatment within 24 months of initial first-line treatment. For the latter group, descriptive statistics of demographic and baseline characteristics and inter-treatment intervals in months as well as Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) following initiation of immunochemotherapy and idelalisib were calculated. Population: Demographic characteristics of these 37 patients included median (range) age at initiation of idelalisib of 64 (33-84) y and 18 (48.6%) females. Histologic grade at diagnosis included 33 (89.2%) with grades 1 or 2 as well as 4 (10.8%) with grade 3A, while 21 (56.8%) patients had a FLIPI score ≥3. The mean (s.d.) number of prior therapies was 3.4±1.4, with a range of 2 to 8, while first-line therapies included 21 (56.8%) patients who received R-CHOP-based regimens, 7 (18.9%) who received BR, and 5 (13.5%) who received R-CVP. Mean (s.d.) inter-treatment intervals included 12.5±6.1 months between first- and second-line for all patients, 9.7±9.3 months between second- and third-line for all patients, 11.9±12.0 months between third- and fourth-line for 24 (64.9%) patients, and 11.8±7.6 months between fourth- and fifth-line for 15 (40.5%) patients. Median (range) time from first-line therapy to idelalisib initiation was 30.3 (8.9-94.7) months; no patient received idelalisib as second-line therapy. Results: Best responses included 5 (13.5%) patients with CR, 16 (43.2%) with PR, 2 (5.4%) with SD, and 1 (2.7%) with PD; median duration of response for those with CR or PR was 11.8 months (95% CI: 3.8 months, not evaluable). There were 7 (18.9%) deaths and 21 (56.8%) PFS events in this group. Estimated probabilities of survival (s.e.) and progression-free status at 2 y following initiation of idelalisib were 79%±7% and 29%±10%, respectively. Median PFS was 11.1 months (95% CI: 5.5, 19.3 months). Estimated probability of survival (s.e.) at 5 years following initiation of first-line treatment was 79%±8%. Median overall survival from both initiation of first-line immunochemotherapy as well as with idelalisib was not reached during the course of this study. Conclusions: Idelalisib may have significant clinical activity in high-risk and doubly-refractive FL following early relapse status post first-line immunochemotherapy. Given the small size of the studied subset population which may not be representative, further characterization in additional patients is warranted to ensure the generalizability of this finding, including consideration of further investigational protocols featuring targeted therapies employed both as single agents and in combination. Figure 1. Overall Survival From Initiation of First-line Treatment Figure 1. Overall Survival From Initiation of First-line Treatment Figure 2. Overall Survival From Initiation of Idelalisib Figure 2. Overall Survival From Initiation of Idelalisib Figure 3. Progression-Free Survival From Initiation of Idelalisib Figure 3. Progression-Free Survival From Initiation of Idelalisib Disclosures Gopal: Gilead, Spectrum, Pfizer, Janssen, Seattle Genetics: Consultancy; Spectrum, Pfizer, BioMarin, Cephalon/Teva, Emergent/Abbott. Gilead, Janssen., Merck, Milennium, Piramal, Seattle Genetics, Giogen Idec, BMS: Research Funding; Millennium, Seattle Genetics, Sanofi-Aventis: Honoraria. Kahl:Roche/Genentech: Consultancy; Seattle Genetics: Consultancy; Millennium: Consultancy; Cell Therapeutics: Consultancy; Celgene: Consultancy; Infinity: Consultancy; Pharmacyclics: Consultancy; Juno: Consultancy. Flowers:Infinity Pharmaceuticals: Research Funding; Genentech: Research Funding; Spectrum: Research Funding; Millennium/Takeda: Research Funding; Seattle Genetics: Consultancy; Spectrum: Research Funding; Pharmacyclics: Research Funding; AbbVie: Research Funding; AbbVie: Research Funding; Gilead Sciences: Research Funding; Pharmacyclics: Research Funding; Onyx Pharmaceuticals: Research Funding; Celegene: Other: Unpaid consultant, Research Funding; OptumRx: Consultancy; Gilead Sciences: Research Funding; Janssen: Research Funding; Acerta: Research Funding; Millennium/Takeda: Research Funding; Acerta: Research Funding; Infinity Pharmaceuticals: Research Funding; Janssen: Research Funding; Onyx Pharmaceuticals: Research Funding. Martin:Janssen: Consultancy, Honoraria; Acerta: Consultancy; Gilead: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Bayer: Consultancy. Link:Genentech: Consultancy, Research Funding; Kite Pharma: Research Funding. Ansell:Bristol-Myers Squibb: Research Funding; Celldex: Research Funding. Ye:Gilead: Employment. Koh:Gilead: Employment. Abella:Gilead: Employment. Barr:Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Abbvie: Consultancy; Gilead: Consultancy. Salles:Calistoga Pharmaceuticals, Inc.; Celgene Corporation; Genentech, Inc.; Janssen Pharmaceutica Products, L.P.; Roche: Consultancy; Celgene Corporation; Roche and Gilead Sciences: Research Funding; Celgene Corporation; Roche: Speakers Bureau.

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Eligibility for second-line therapy in patients with advanced hepatocellular carcinoma (aHCC): A BC Cancer population-based study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.491 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 491-491

Author(s):

Erica S. Tsang ◽

Janine Marie Davies ◽

Jonathan M. Loree ◽

Howard John Lim ◽

Daniel John Renouf ◽

...

Keyword(s):

Real World ◽

Cox Regression ◽

High Rate ◽

Advanced Hepatocellular Carcinoma ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Line Therapy ◽

First Line Treatment

491 Background: Evidence supporting second-line therapies has become available for aHCC, including regorafenib, cabozantinib, ramucirumab, and nivolumab. The optimal second-line treatment regimen is unknown, and there remains limited real-world data about the eligibility of patients for second-line therapies in aHCC. We aimed to characterize the real-world eligibility and use of second-line therapies post sorafenib. Methods: We identified all patients with aHCC who received ≥1 cycle of first-line sorafenib between January 1, 2014 and December 31, 2017 across 6 centers in British Columbia (BC), Canada. All patients were required to be Child-Pugh class A for initiation of sorafenib in BC. Baseline characteristics and clinical outcomes were reviewed. Eligibility for second-line therapy was determined using the RESORCE and CELESTIAL study entry criteria. Results: Of 144 patients with advanced HCC who received ≥1 cycle of first-line sorafenib, median age was 65.3 years (range 32.2-83.4) and 85% were male. Median duration of sorafenib was 2.6 months. 12 patients (8%) went on to receive second-line treatment. 37 patients (26%) were deemed eligible for second-line systemic therapy. Primary reasons for ineligibility included ECOG ≥2 (58%), and deterioration to Child-Pugh status B (28%). On Cox regression, improved survival was associated with better ECOG and recurrent disease. (Table). Kaplan-Meier analysis demonstrated that eligibility for second-line treatment was associated with improved median overall survival from end of first-line treatment (8.5 vs. 5.1 months; p<0.01). Conclusions: Only a minority of real-world patients with aHCC were eligible for second-line therapies based on second-line trial criteria. Given the high-rate of attrition, improved first-line treatment options are urgently needed. [Table: see text]

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Efficacy and Toxicity of Addition of Bevacizumab to Chemotherapy in Patients with Metastatic Colorectal Cancer

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207322666190119162352 ◽

2019 ◽

Vol 21 (10) ◽

pp. 718-724 ◽

Cited By ~ 2

Author(s):

Wen-Cong Ruan ◽

Yue-Ping Che ◽

Li Ding ◽

Hai-Feng Li

Keyword(s):

Colorectal Cancer ◽

Adverse Event ◽

Metastatic Colorectal Cancer ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Clinical Prognosis ◽

Line Therapy ◽

Significant Difference

Background: Pre-treated patients with first-line treatment can be offered a second treatment with the aim of improving their poor clinical prognosis. The therapy of metastatic colorectal cancer (CRC) patients who did not respond to first-line therapy has limited treatment options. Recently, many studies have paid much attention to the efficacy of bevacizumab as an adjuvant treatment for metastatic colorectal cancer. Objectives: We aimed to evaluate the efficacy and toxicity of bevacizumab plus chemotherapy compared with bevacizumab-naive based chemotherapy as second-line treatment in people with metastatic CRC. Methods: Electronic databases were searched for eligible studies updated to March 2018. Randomized-controlled trials comparing addition of bevacizumab to chemotherapy without bevacizumab in MCRC patients were included, of which, the main interesting results were the efficacy and safety profiles of the addition of bevacizumab in patients with MCRC as second-line therapy. Result: Five trials were eligible in the meta-analysis. Patients who received the combined bevacizumab and chemotherapy treatment in MCRC as second-line therapy showed a longer overall survival (OS) (OR=0.80,95%CI=0.72-0.89, P<0.0001) and progression-free survival (PFS) (OR=0.69,95%CI=0.61-0.77, P<0.00001). In addition, there was no significant difference in objective response rate (ORR) (RR=1.36,95%CI=0.82-2.24, P=0.23) or severe adverse event (SAE) (RR=1.02,95%CI=0.88-1.19, P=0.78) between bevacizumab-based chemotherapy and bevacizumabnaive based chemotherapy. Conclusion: Our results suggest that the addition of bevacizumab to the chemotherapy therapy could be an efficient and safe treatment option for patients with metastatic colorectal cancer as second-line therapy and without increasing the risk of an adverse event.

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Characteristics, treatment patterns, and economic burden of patients with metastatic cervical cancer receiving systemic anticancer therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.39.28_suppl.51 ◽

2021 ◽

Vol 39 (28_suppl) ◽

pp. 51-51

Author(s):

Xiaoyun Pan ◽

Lincy S. Lal ◽

John White ◽

Seyed Hamidreza Mahmoudpour ◽

Christian Valencia

Keyword(s):

Cervical Cancer ◽

Economic Burden ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Duration Of Treatment ◽

Second Line Therapy ◽

Treatment Regimens ◽

Line Therapy

51 Background: In 2021, 14,480 patients are estimated to be diagnosed with cervical cancer in the US; 16% of patients are expected to have metastatic disease for whom the 5-year survival rate is 17.6% per SEER estimates. Patients with metastatic cervical cancer (mCC) are treated mainly with systemic therapy. This study aims to describe the clinical characteristics, demographics, treatment patterns, and economic burden of patients with mCC receiving systemic therapy. Methods: Eligible women had been diagnosed with cervical cancer, as evidenced by >2 outpatient or >1 inpatient claim in the Optum Research Database from January 2014 through January 2020. Patients were included if they had metastasis within 6 months before or after cervical cancer diagnosis, with evidence of systemic treatment on or after the latter of a claim date for cervical cancer disease or metastatic disease. The index date was the first-line treatment initiation date. Patients were required to have ≥6 months of pre-index continuous enrollment. The top 3 treatment regimens and median treatment duration by line of therapy were described. All-cause per-patient-per-month (PPPM) costs (2019 US dollars), including plan and patient paid amounts, were reported for full follow-up period from first-line and second-line therapy initiation. Results: The study sample consisted of 778 patients (mean age, 59 years; commercial, 58%; Medicare Advantage, 42%). The mean (median) follow-up period was 14 (9) months. Top baseline comorbidities were diseases of the urinary system (71%) and diseases of the female genital organs (70%), and the median Charlson comorbidity index was 7. In the first line, 80% of patients received platinum-based therapy and 23% received bevacizumab (bev). Of 778 patients, only 294 (38%) received second-line therapy, with 34% receiving bev. Top first-line treatment regimens were carboplatin + paclitaxel (27%), cisplatin (21%), and bev + carboplatin + paclitaxel (10%); the median (95% CI) duration of treatment was 3.4 (3.1-3.7) months. Top second-line treatment regimens were bev + carboplatin + paclitaxel (13%), carboplatin + paclitaxel (11%), and pembrolizumab (6%); the median duration of treatment was 3.8 (3.1-4.2) months. Mean all-cause total PPPM costs were $19,519 from first-line and $22,660 second-line therapy initiation (table). Conclusions: This study indicates that real-world mCC patients have short treatment durations and significant economic burden with first-line and second-line therapy. Novel therapies associated with greater clinical benefits in patients with mCC may provide economic benefit.[Table: see text]

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