Impact of Second-Generation Tyrosine Kinase Inhibitors As Second Line Treatment for Patients with Chronic Myeloid Leukemia,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3780-3780 ◽  
Author(s):  
J Valentin Garcia-Gutierrez ◽  
Pilar Herrera ◽  
Lorena L Abalo ◽  
Maria Dolores Rey ◽  
Maria Calbacho ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Second Generation ◽  
Kinase Inhibitors ◽  
Salvage Treatment ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Group 2 ◽  
Group 1

Abstract Abstract 3780 Background: Imatinib has shown an outstanding improvement in the prognosis of chronic myeloid leukemia (CML) patients. Nevertheless, some of them have proven to be resistant or intolerant to imatinib. For these patients, second-generation tyrosine kinase inhibitors (TKIs) are available. These drugs may be indicated in different circumstances as primary or second resistance, suboptimal responses or intolerance.The real benefits of second-generation TKIs as salvage treatment are surely in dependence with the indication in each case and are, therefore, difficult to evaluate. Second-generation TKIs are being evaluated as first line treatment compared to imatinib with quite favourable outcomes so long, but have not yet been compared with a strategy combining imatinib followed by second-generation TKIs for patients with previous unfavourable responses. Aims: Evaluate the real benefit of second-generation TKIs in second line treatment for CML patients regardless of the indication for its use. Study groups and methods: We have studied 98 patients treated with imatinib as first tyrosin kinase inhibitor (TKI) in our centre. These patients have been classified according whether second-generation TKIs were available or not. Group 1 includes 60 patients treated since 2001 to 2005, when the only salvage treatment was an increased imatinib dose, chemotherapy or allogenic stem cell transplantation. Group 2 includes 38 patients treated since 2005 until today. In the second group second-generation TKIs (dasatinib or nilotinib) were used according to the indications mentioned above. Follow up period was 39 months and 32 months for group 1 and 2 respectively. Sokal risk index was high in 14% and 16%; intermediate 42 % and 40%; and low in 44% and 44 % for group 1 and 2 respectively. Results: The use of second-generation TKIs as second line resulted in significant benefit to patients in terms of responses. Complete cytogenetic responses (CCR) at any time were achieved in 73% and 86% for patients in group 1 and 2 (p=.09). Probability of the achievement of mayor molecular responses (MMR) was 42% vs 71% for group 1 and 2 respectively [p=.009; ratio=0.3 (0.1–0.7)]. Response rates at the last follow up for group 1 and 2 were: MMR: 33% vs 62%; CCR: 68% vs 94% and failure 32% vs 6% (p=.008). Progression free survival (including all the patients who started treatment) was 88% vs 94% for group 1 and 2 respectively. We found no correlation among responses and some prognostic factors (Sokal index, mutations at the TK domain or imatinib plasma levels). Imatinib doses were increased in 21 patients (35%) in group 1 (reasons for increasing doses were failure in 14 patients and suboptimal responses in 7 patients). 10 patients (26%) in group 2 received second-line TKIs as second line treatment (4 because imatinib failure, 3 by suboptimal responses and 3 due to intolerance). Conclussions: The use of second-generation TKIs as salvage has improved the responses of CML patients treated with TKIs. Once the second-generation TKIs has shown benefit compared to imatinib in first line treatment, this therapeutic strategy should be compared vs the use of imatinib followed of second-line TKIs for patients without optimal responses to imatinib. Disclosures: Montalban: Red Temática de Investigación Cooperativa en Cancer (RETICC): Research Funding; Asociación Española contra el Cancer: Research Funding.

Frequency of Complete Molecular Response In Chronic Myeloid Leukemia Patients In Real Life Practice.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1227-1227
Author(s):  
Matthieu Decamp ◽  
Dina Istasi ◽  
Atchroue Johnsonansah ◽  
Oumedaly Reman ◽  
Xavier Levaltier ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Molecular Response ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Line Therapy ◽  
Ifn Treatment ◽  
Complete Molecular Response

Abstract Abstract 1227 Introduction: Scarce data are available on the frequency of complete molecular response (CMR) in chronic myeloid leukemia (CML) patients. The European Leukemia Net defined CMR lately as an undetectable transcript quantified by Real Time PCR and/or nested PCR in two consecutive blood samples of adequate quality, using strict sensitivity criteria (sensitivity > 10 4). CMR is the best response that we can achieve in CML patients. Generally it is obtained after hematopoietic stem cell transplantation (HSCT) but since the administration of tyrosine kinase inhibitors (TKI), the number of patients seen with CMR is continuously increasing. The aim of this study is to assess the frequency of CMR in CML patients, and study their characteristics. Methods: A retrospective study was conducted to collect epidemiological, clinical, therapeutic and laboratory data of CML patients followed in hospitals of the region of Basse Normandie in France. All CML patients who had been followed up, between 1999 and 2010, by molecular monitoring for their Bcr-Abl transcript level were included. Clinical and biological responses were defined according to the ELN 2009 recommendations. Results: 199 patients were included in this study, 154 were diagnosed during the study period. Median age at diagnosis was 54 years and 46% were females. 61.3% were diagnosed in the chronic phase while the accelerated and the blast crisis phase accounted for 10.5% and 0.02%. Among these patients, 2 had the p190 BCR-ABL transcript and 2 the p230 transcript type. 169 were still followed at the end of this study and the median follow up duration was 6,4 years. Out of these 199 patients 12 died and 18 were lost out of sight. Imatinb (IM) alone or Imatinib-based combined therapies in clinical trials, was administrated as a first line treatment in 51,2% of patients. Interferon (INF) alone or in association with other chemotherapy was the frontline therapy in 37,7%; 52% of them started IFN treatment before 2000 and 73% switched to IM. At the time of analysis 26.6% of patients achieved a complete molecular response and 39.7% obtained a major molecular response (MMR) as defined by the international scale; this figure is to be tempered by the fact that the follow up duration was less than 18 months for 9,5% of patients. CMR was obtained in 11 patients following HSCT. With IM as a first line therapy, 11 patients achieved CMR or had an undetectable transcript after a median duration of 43.3 months and lasted for 13.3 months. When IM was given as a second line therapy, 17 obtained a CMR or had an undetectable transcript, in this case the median time calculated starting from the second line treatment administration was 37,3 months and in half of them, it persisted for 28 months. Among these patients, two discontinued therapy and currently they are still on CMR, 24 and 18 months after IM arrest. There was no significant difference in the median CMR achievement duration between the first and second line IM therapy groups. CMR following IFN treatment had been observed in 8 patients, 7 of them stopped IFN and have been in CMR for more than 5 years since its discontinuation. Finally five patients achieved a CMR after administration of second generation TKI. Altogether, a total of 63 patients were followed up for undetectable BCR-ABL transcript. In 53, the transcript remained undetectable; whereas 10 had lost that level of molecular response; 7 of them had regressed to a MMR though they were under IM therapy; 2 lost the MMR, one of them after IM arrest and one progressed to acute leukemia. Conclusion: A significant proportion of patients is in CMR or at least had no detectable transcript. In case of TKI therapy, the response is obtained after continuous administration (median duration was 36 months) and is durable in most cases. In this study, few patients in CMR have discontinued treatment but maintained their CMR response. Unfortunately one stopped the treatment and relapsed rapidly. The maintenance of this level of response appears to be dependent on continued suppression of the Bcr-Abl clone by TKI. Disclosures: No relevant conflicts of interest to declare.

scholarly journals A Multicenter, Prospective Study for Pediatric Chronic Myeloid Leukemia in Chronic Phase: The JPLSG CML-08 Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3605-3605
Author(s):  
Hiroyuki Shimada ◽  
Akihiro Watanabe ◽  
Masaki Ito ◽  
Chikako Tono ◽  
Haruko Shima ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Myeloid Leukemia ◽  
Second Generation ◽  
Chronic Phase ◽  
Line Treatment ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
First Line Treatment

Abstract Background: Tyrosine kinase inhibitor (TKI) has been used in pediatric chronic myeloid leukemia (CML) for more than 10 years, but only a few prospective clinical studies have been conducted in pediatric patients with CML due to their rarity. We conducted the JPLSG CML-08 study to determine the efficacy and tolerability of TKIs in children and adolescents with newly diagnosed CML in chronic phase (CML-CP). Methods: The JPLSG CML-08 study was a prospective multicenter observational study (UMIN000002581). Patients under 18 years of age with untreated BCR-ABL1-positive CML-CP were eligible and treated according to the modified ELN-2009 recommendation, and the efficacy and safety of TKIs were evaluated. Results: From October 2009 until September 2014, 79 patients were enrolled in 46 hospitals in Japan. A total of 78 patients (49 males and 29 females) were eligible for inclusion. Median age at diagnosis was 11 years (range, 1-17). Median observational period for survivors was 82 months (range, 48-118). Median WBC, Hb and platelet counts were 275x10 9/L (range, 8-765), 9.6g/dL (range, 5.8-14.6) and 560x10 9/L (range, 110-2875), respectively. Splenomegaly was found in 76%. High risk of Sokal, Hasford, EUTOS, and ELTS scores were observed in 21, 13, 27, and 9%, respectively. Clonal chromosome abnormalities in Ph-positive cells occurred in 1 patient at diagnosis. Imatinib, dasatinib, and, nilotinib were used as a first-line treatment in 69 (88%), 7 (9%), and 2 (3%) patients, respectively. The median initial dose of imatinib, dasatinib, and nilotinib was 276, 63, and 262mg/m2, respectively. 5y-PFS and OS was 96.2% (95%CI, 88.6 to 98.7%) and 97.4% (95%CI, 90.1 to 99.4%), respectively. Deaths were observed in 2 patients due to transplant complications. Hematopoietic cell transplantation was conducted in 14 patients (18%). Nine patients (12%) discontinued TKI with the aim of treatment-free remission (TFR), and five of them achieved TFR. In 69 patients with first-line imatinib, complete hematologic response was achieved in 95.7% at 3 months, complete cytogenetic response in 75.4% at 12 months, major molecular response (MMR) in 40.1% at 18 months, and MR4.0 in 52.8% at 60 months; If a transplant was performed, the follow-up period was censored at the date of transplant. Of the 69 patients, 52% changed treatment from imatinib to another TKI or transplant due to poor response, and 20% did due to intolerance. The most common cause of intolerance to imatinib was musculoskeletal events. BCR-ABL1 (IS) <10% at 3 months strongly correlated with higher achievement of MMR, MR4.0, and MR4.5. The EUTOS score was significantly associated with achievement of IS <10% at 3 months. Patients with a first-line second-generation TKI had a higher cumulative incidence of MR4.5 (P = 0.0191) than patients with a first-line imatinib. Second-generation TKI was used as first-line therapy only in patients older than 9 years, but other clinical characteristics, including risk scores, did not differ significantly between the two groups. The incidence of grade 3/4 adverse events (≥ 10%) included neutropenia (47%), anemia (39%), leukopenia (13%), arthralgia (13%), and myalgia (11%) for imatinib, neutropenia (21%), anemia (13%), and thrombocytopenia (11%) for dasatinib, and neutropenia (14%), elevated ALT (14%), hyperbilirubinemia (14%), skin rash (14%), and high CPK (14%) for nilotinib. Gastrointestinal bleeding was an adverse event specific to dasatinib (11% in all grades). Conclusion: This clinical study extends and confirms previous data showing that first-line treatment with imatinib is effective in children and adolescents, with response rates similar to those seen in adults. Although longer follow-up is needed to fully assess the long-term toxic effects, adverse events with imatinib, dasatinib, and nilotinib have been acceptable. As reported in adults, there was an advantage in selecting second-generation TKI over imatinib as first-line therapy to achieve deep molecular remission (DMR). Since discontinuation of TKI after achieving DMR is the preferred strategy, second-generation TKI is expected to become the standard therapy for children and adolescents. Disclosures No relevant conflicts of interest to declare.

Late Appearance of 14q32/IGH Translocation in Chronic Lumphocytic Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2429-2429
Author(s):  
Francesco Cavazzini ◽  
Gian Matteo Rigolin ◽  
Lara Rizzotto ◽  
Antonella Bardi ◽  
Elisa Tammiso ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clonal Evolution ◽  
Fish Analysis ◽  
Line Treatment ◽  
First Line ◽  
Group 2 ◽  
First Line Treatment ◽  
14Q32 Translocation ◽  
Group 1

Abstract Abstract 2429 Up to 80% of Chronic Lymphocytic Leukemia (CLL) harbour clonal chromosome aberrations having important clinical implications (i.e. 13q deletion, +12, 11q/ATM and 17p/TP53 deletions). 14q32/IGH rearrangements were recently found in 6–19% of CLL patients and were associated with therapy-demanding disease and inferior outcome. Whereas evidence was provided that some of the classical aberrations, such as 11q-, 17p-, may appear late in CLL clinical history, no information is presently available concerning 14q32/IGH translocations. The aim of this study was i) to analyze the incidence of 14q32/IGH translocations occurring at clonal evolution in CLL, ii) to analyze the clinicobiologic significance of late-appearing 14q32/IGH translocations. One hundred-five CLL cases seen at our institution in a 10-year period were submitted to FISH analysis at diagnosis or before 1st line treatment as part of routine diagnostic workup. In 47 patients with indolent disease (untreated or treated with 1 line without relapse, group 1) FISH analysis was repeated after 48–96 months (median 72). In 58 relapsed patients who started 2nd line treatment (group 2), FISH was performed sequentially before administration of the 2nd line and before each subsequent line of therapy. These 105 patients fulfilled the following criteria: a) diagnosis of bona fide CLL based on morphology and immunophenotyping (CD5/CD19+, CD23+ as minimal requirement), b) clinical records available for review, c) successful FISH analysis at diagnosis and during follow-up. Those cases with t (11;14)(q13;q32)/CCND1-IGH or other 14q32/IGH translocations present at diagnosis were excluded from this study. Sequential FISH studies were performed in all patients on peripheral blood (PB) samples using commercially available probes for the identification of deletions at 13q14, 11q22/ATM, 17p13/TP53, of trisomy 12 and of 14q32/IGH translocations. In 10 patients bone marrow (BM) aspiration and/or lymph node (LN) biopsy were studied by FISH as well. The patients were treated at disease progression as defined by NCI criteria. Refractory disease was defined by stable disease or progressive disease during treatment or disease progression within 6 months of from antileukemic treatment using fludarabine alone or in combination with other agents. Time to chemorefractoriness was measured from date of first line treatment to date of refractoriness to fludarabine containing regimen or date of last follow-up. Overall survival was measured from diagnosis to date of last follow-up or death and from initiation of first line treatment to the date of death or last follow-up. At diagnosis 39% of the cases had 13q-, 14% had +12, 7% had 11q- and 3% had 17p-. A late-appearing 14q32/IGH rearrangement was not detected among 47 patients in group 1, whereas 7/58 cases (12,1%) in group 2 showed a 14q32/IGH break in 16–25% of the cells. These 7 patients had the following aberrations at diagnosis: 13q- and 11q- in 1 case, 13q- in 2 cases; 11q- in 1 case, +12 in 2 cases, no aberrations 1 case. The 14q32 translocation appeared after a median time of 64 months (range 51–91). It was associated with the appearance of 17p- in 3/7 cases with one of these presenting also biallelic del13q. In two cases paired BM or LN sample and PB samples were available for FISH studies and the appearance of IgH translocation in the BM or in the LN sample preceded its appearance in PB by 13–58 months. All 7 cases with late appearing 14q32/IGH translocation developed chemorefractoriness to fludarabine regimen with a median TTC of 27 months (range 12–40 months), as compared with a TTC of 67 months (range 1–143 months) in 51 treated patients who did not develop the 14q32 translocation (p=0.0002). Overall survival did not differ significantly either when measured from diagnosis or from 1st line treatment in 7 patients with 14q32 translocation as compared with the appropriate control. We arrived at the following conclusions: i) a late-appearing 14q32/IGH translocation occurred at a relatively high incidence (12,1%) in patients with relapsing disease and not in patients with stable disease, ii) this aberration involved a minority of cells and, in approximately half of the cases, it was associated with other aberrations, reflecting complex clonal evolution, iii) in 2 assessable cases it first appeared first in the BM or LN; iv) the appearance of 14q32/IGH translocation was associated with shorter TTC. Disclosures: No relevant conflicts of interest to declare.

Novel Agents Versus Conventional Drugs for the Treatment of Relapsed Multiple Myeloma Patients: Experience of a Single Center over the Last 25 Years

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5385-5385
Author(s):  
Sara Grammatico ◽  
Elisabetta Lisi ◽  
Laura Cesini ◽  
Maria Letizia Vallone ◽  
Saveria Capria ◽  
...  
Keyword(s):  
Real Life ◽  
Novel Agents ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Number Of Patients ◽  
Group 2 ◽  
Group 1

Abstract Background: New active classes of drugs such as proteasome inhibitors (e.g., bortezomib) and immunomodulatory drugs-IMiDs (e.g., thalidomide and lenalidomide) are nowadays the standard treatment for multiple myeloma (MM) patients, alone or in association with old agents. The achievement of deeper responses, using novel agents instead of conventional treatment, is a significant prognostic factor for the outcome of these patients, resulting in an improved overall survival (OS) and progression-free survival (PFS). Here, we report the single center real life comparison between the outcome achieved with old agents with that obtained with novel agents in young MM patients treated at first relapse over a 25-year period. Patients and Methods: We analyzed a cohort of 258 young (median age 55 years; range 19-69) newly diagnosed MM patients treated at our Center between August 1989 and November 2014. All patients received old or novel agents followed by autologous hematopoietic stem cell transplantation (single or tandem) as first line treatment. Of the 258 patients, 144 experienced a progression of disease after a median of 34 months (range 7-195) and received old or novel agents as second line therapy. Old agents used as first and second line treatment were prevalently vincristine, doxorubicin and dexamethasone (VAD), melphalan and prednisone (MP) or cyclophosphamide and dexamethasone (CD); novel agents included velcade-based or IMiD-based regimens. Our cohort was divided into four different groups: 1) 51 patients treated with old agents as first and second line therapy (35.4%);2) 79 patients treated with old agents as first line therapy and novel agents as second line therapy (54.8%);3) 2 patients treated with novel agents in induction therapy and subsequently with old agents as second line therapy (1.4%);4) 12 patients treated with novel agents both in first and second line (8.3%). Our analysis focused on groups 1 and 2; group 3 was not considered for the small number of patients and because the choice of treatment was based exclusively on a worsening of the clinical condition; group 4 was not included for the small number of patients and because of the short follow-up. Our aim was to compare the results obtained in patients treated only with old agents both as first and second line treatment with the outcome of patients who received old agents as first treatment and novel agents as second line treatment, to assess the impact of novel agents in real life MM patients' management. Results: The OS at 5 years for patients of group 2 was significantly higher than that of group 1 patients (41.6% vs 14.1%); even at 10 years, the OS was significantly better for group 2 (20.4% vs 2.4%, p<0.0001); median OS was 4.1 years for group 2 and 1.4 years for group 1. The PFS was superior for patients treated with novel agents as second line treatment both at 5 years (12% vs 6.9%) and at 10 years (10% vs 2.3%) (p=0.02); median PFS was 1.4 years for group 2 and 0.7 for group 1. PFS2, considered as the interval from the start of first line treatment to the date of second relapse, showed also significantly better results for group 2 patients compared to group 1 patients both at 5 (61.8% vs 33.3%) and 10 years (25.7% vs 9.2%). Median PFS2 was 6.8 years for group 2 and 3.7 years for group 1(p=0.0002). Conclusions: We analyzed the effect of the introduction of novel agents in a cohort of young MM patients treated at our Center over a 25-year period, between 1989 and 2014. Patients treated in the earlier years received old agents both as first and second line treatment, while in more recent years all patients who experienced a relapse were treated with novel agents as second line treatment. Our analysis underlines that patients receiving novel agents witnessed a significantly better OS and PFS compared to patients treated only with old agents. When focusing on PFS2, we could determine that the duration of response obtained with proteasome inhibitors and IMiDs was significantly longer than that obtained with conventional chemotherapy. This currently ongoing study and a longer follow-up in a larger number of group 4 patients will allow to conclusively define the true real life impact of novel agents when used both as first and second line treatment for the management of young MM patients. Disclosures Petrucci: Celgene, Janssen-Cilag, Amgen, Mundipharma, BMS: Honoraria.

A REVIEW ON THE ROLE OF TYROSINE KINASE INHIBITORS AVAILABLE FOR THE MANAGEMENT OF CHRONIC MYELOID LEUKEMIA

2020 ◽  
Vol 7 (2) ◽  
pp. 205-211
Author(s):  
Kaynat Fatima ◽  
Syed Tasleem Raza ◽  
Ale Eba ◽  
Sanchita Srivastava ◽  
Farzana Mahdi
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Protein Kinases ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

The function of protein kinases is to transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Many of these kinases are linked to the initiation and development of human cancer. The recent development of small molecule kinase inhibitors for the treatment of different types of cancer in clinical therapy has proven successful. Significantly, after the G-protein-coupled receptors, protein kinases are the second most active category of drug targets. Imatinib mesylate was the first tyrosine kinase inhibitor (TKI), approved for chronic myeloid leukemia (CML) treatment. Imatinib induces appropriate responses in ~60% of patients; with ~20% discontinuing therapy due to sensitivity, and ~20% developing drug resistance. The introduction of newer TKIs such as, nilotinib, dasatinib, bosutinib, and ponatinib has provided patients with multiple options. Such agents are more active, have specific profiles of side effects and are more likely to reach the necessary milestones. First-line treatment decisions must be focused on CML risk, patient preferences and comorbidities. Given the excellent result, half of the patients eventually fail to seek first-line treatment (due to discomfort or resistance), with many of them needing a third or even further therapy lines. In the present review, we will address the role of tyrosine kinase inhibitors in therapy for chronic myeloid leukemia.

Etiology of Cartilage Lesions Does Not Affect Clinical Outcomes of Patellofemoral Autologous Chondrocyte Implantation

Cartilage ◽  
2021 ◽  
pp. 194760352110309
Author(s):  
Alexandre Barbieri Mestriner ◽  
Jakob Ackermann ◽  
Gergo Merkely ◽  
Pedro Henrique Schmidt Alves Ferreira Galvão ◽  
Luiz Felipe Morlin Ambra ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Autologous Chondrocyte Implantation ◽  
Second Generation ◽  
Cartilage Lesion ◽  
Chondrocyte Implantation ◽  
Group 3 ◽  
Group 2 ◽  
Autologous Chondrocyte ◽  
Group 1

Objective To determine the relationship between cartilage lesion etiology and clinical outcomes after second-generation autologous chondrocyte implantation (ACI) in the patellofemoral joint (PFJ) with a minimum of 2 years’ follow-up. Methods A retrospective review of all patients that underwent ACI in the PFJ by a single surgeon was performed. Seventy-two patients with a mean follow-up of 4.2 ± 2.0 years were enrolled in this study and were stratified into 3 groups based on the etiology of PFJ cartilage lesions: patellar dislocation (group 1; n = 23); nontraumatic lesions, including chondromalacia, osteochondritis dissecans, and degenerative defects (group 2; n = 28); and other posttraumatic lesions besides patellar dislocations (group 3; n = 21). Patient’s mean age was 29.6 ± 8.7 years. Patients in group 1 were significantly younger (25.4 ± 7.9 years) than group 2 (31.7 ± 9.6 years; P = 0.025) and group 3 (31.5 ± 6.6 years; P = 0.05). Body mass index averaged 26.2 ± 4.3 kg/m2, with a significant difference between group 1 (24.4 ± 3.2 kg/m2) and group 3 (28.7 ± 4.5 kg/m2; P = 0.005). A clinical comparison was established between groups based on patient-reported outcome measures (PROMs) and failure rates. Results Neither pre- nor postoperative PROMs differed between groups ( P > 0.05). No difference was seen in survivorship between groups (95.7% vs. 82.2% vs. 90.5%, P > 0.05). Conclusion Cartilage lesion etiology did not influence clinical outcome in this retrospective study after second generation ACI in the PFJ. Level of Evidence Level III, retrospective comparative study.

scholarly journals Sequential Treatment of Metastatic Adenocarcinoma of the Pancreatic Duct with Liver Metastasis Following the NAPOLI-1 Study Protocol with nal-Irinotecan plus 5-FU in the Second Line

2020 ◽  
Vol 13 (1) ◽  
pp. 79-84
Author(s):  
Dilara Akhoundova Sanoyan ◽  
Cäcilia S. Reiner ◽  
Panagiota Papageorgiou ◽  
Alexander R. Siebenhüner
Keyword(s):  
Systemic Treatment ◽  
Sequential Treatment ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Curative Surgery ◽  
To Receive

Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at an advanced or metastatic stage, when curative surgery is not recommended. Therefore, the prognosis is poor for this dismal disease, with only 1–2% of the patients reaching the 5-year survival follow-up. Current advances in systemic treatment with gemcitabine regimens, specifically polychemotherapy with gemcitabine plus nab-paclitaxel or other multidrug regimens such as FOLFIRINOX in the first line, have improved disease control over time. This higher efficacy of systemic treatment enables metastatic PDAC patients to receive second-line treatment more often nowadays. Currently, there is only one regimen for second-line treatment approved by the EMA, FDA, and Swissmedic, based on the phase III NAPOLI-1 study. In this case report, we present an outstanding response to sequential treatment with gemcitabine plus nab-paclitaxel followed by second-line treatment with nal-irinotecan plus 5-fluorouracil.

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

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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