bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the costs of bevacizumab plus cisplatin and gemcitabine versus cetuximab plus vinorelbine and cisplatin in patients with advanced non-small cell lung cancer (NSCLC) in France: Results from a cost modelling study
Authors: Chouaid C. , Vergnenègre A. , Florentin V. , Walzer S.
Published: August 2020

e17560

Background: New treatment options for advanced NSCLC can offer improved survival over standard chemotherapy (CT). Bevacizumab (BEV), a humanized monoclonal antibody (MAb) directed against VEGF when combined with CT increases overall survival (median 13.6 months in the AVAiL study) and progression-free survival (PFS) in patients with advanced NSCLC compared with CT alone. Cetuximab (CTX), an IgG1 MAb which targets the epidermal growth factor receptor, achieved a median survival of 11.3 months when combined with CT in the FLEX study; marketing authorization is anticipated during 2009. The aim of this study was to compare the costs of treating patients with BEV plus cisplatin and gemcitabine (BCG) versus CTX plus vinorelbine and cisplatin (CVC) in France. Methods: A Markov model was used to compare drug and administration costs associated with treating advanced NSCLC with either BCG or CVC. The model assumes patients move from non-progressive to progressed disease to death, according to transition probabilities derived from an indirect comparison of the efficacy of BCG and CVC in terms of PFS using data from the respective pivotal trials and appropriate indirect comparison methodology. Cost data were derived from local sources. Drug costs assumed CT was given for up to 6 cycles, that CTX was administered at an initial dose of 400 mg/m2 followed by 250 mg/m2 weekly until progression and that BEV was administered at 7.5 mg/kg every 3 weeks until progression. The model estimated average drug and administration costs per patient treated with either BCG or CVC. Results: The mean cost for BCG and CVC was €23849 and €35678 respectively, resulting in a saving of €11829 per patient for BCG. The acquisition of BEV was less costly than the acquisition of CTX (€15374 vs €23530) and, BCG acquisition and administration costs were lower than CTX's respectively, €19756 versus €24750 and €4093 versus €10928. Conclusions: Targeted therapy using BEV is less costly than CTX in France, and therefore, from a budget perspective offers the best value for money approach to improving outcomes in patients with advanced NSCLC.

[Table: see text]
Implementation of an integrated cancer care network
Authors: Latreille J. , Samson A. , Tran U. , Mimeault C. , Boily C. , Laflamme B. , Loutfi A.
Published: August 2020

e17564

Background: In 1998, the province of Quebec adopted its cancer control program (CP). Its goal was to establish a hierarchical and integrated cancer network of interdisciplinary teams. In 2004, a team evaluation process was initiated by the Direction de la lutte contre le cancer (ministry of health) to help implement this program. Methods: The evaluation consisted of completion of a matrix by the requesting team, a visit by a multidisciplinary group of experts and a report card. Three levels of expertise were assessed: core (all), regional (regional hospitals), and supraregional (tumor specific/complex situations). The matrix was based on the fundamental orientations of the CP, thus setting the framework for patient centered care. The conformity indicators were mainly structural and process oriented. In order to be evaluated for the subsequent mandates, teams had to conform to the core mandate. Those who did not succeed had one year to reapply. Mandates are for 4 years. Results: Teams were able to comply with most of the elements of the evaluation matrix. Sessions for clarification and coaching about this new interdisciplinary approach were necessary and helpful. A total of 153 visits were done:70 for core, 8 for regional and 75 for supraregional mandates respectively. Major health institutions such as university hospitals applied for multiple supraregional team designation. In all, 130 teams had their designation confirmed. This process highlighted some common weaknesses such as the lack of use of data for quality control. Conclusions: Acceptance of this hierarchical cancer care model was facilitated by the fact that it was in line with the integrated health care network of Quebec. The evaluation process has had an impact on the way cancer care is delivered in Quebec. This initial phase has helped implement an interdisciplinary patient centered model of care in line with the CP. Participation of different experts has also helped foster knowledge transfer and appropriation of the process. Impact on patient care and satisfaction remains to be assessed. An initial patient's questionnaire has been completed in 2008 and will serve as a control to future surveys.

No significant financial relationships to disclose.
Validation of a global self-assessment and peer-review quality programme dedicated to comprehensive cancer centres: A method to assess, improve and promote quality of integrated care, research, and education in cancer centers
Authors: Saghatchian M. , Hummel H. , Otter R. , de Valeriola D. , van Harten W. , Paradiso A. , Lovey J. , Kasler M. , Fumoleau P. , Ringborg U. , Tursz T.
Published: August 2020

e17565

Background: Oncology is a specialty requiring a combination of multidisciplinary expertises, novel technology, integration of innovation into care and research efforts in order to improve the quality of life and survival of patients. Provision of high-quality care and improvement of disease outcome should be promoted in cancer centers. Methods: The Organization of European Cancer Institutes developed an Accreditation Programme combining: 1-a quantitative questionnaire assessing the human, technical and financial resources and activities in care, research and education dedicated to oncology; 2- a set of standards and criteria for high-quality cancer management integrated in an electronic tool with a scoring system of compliance; 3- a peer-review process for review of the self-assessment outcome and on-site visits; 4- a report and improvement plan allowing to designate comprehensive cancer centers complying with required criteria for high-quality comprehensive cancer patient management. All components of the Accreditation Programme were tested in 8 different voluntary cancer centers in Europe. The objectives were to assess the feasibility, reproducibility and acceptance of the Accreditation Programme; to improve the standards and criteria in terms of understanding and consensus; to validate the peer review methodology and establish a method for reporting and implementing an improvement plan; to provide with a preliminary system of designation of comprehensive cancer centers based on criteria of high-quality integrated research, care and education. Results: The 2 consecutive pilot tests allowed to validate 1- relevant items for the quantitative questionnaire; 2-criteria and standards for high-quality integrated multidisciplinary cancer patient's management. 3-The impact of the Accreditation Programme on improvement of patients management and professionals involvement. Conclusions: The OECI Accreditation Programme is ready for dissemination. Participation to the Programme allows development of improvement plans for innovative and integrated comprehensive cancer patients management in cancer centers.

No significant financial relationships to disclose.
The financial implications of a conversion from enoxaparin to dalteparin as the LMWH of choice at a comprehensive cancer center
Authors: Patterson S. G. , Johnson P. , Bradbury B. , Tata J. , Quilitz R. , Carlton R. , Bramley T. , Wetzstein G.
Published: August 2020

e17566

Background: To assess the financial implications of a conversion from enoxaparin to dalteparin as the low molecular weight heparin (LMWH) of choice at a large, comprehensive cancer center. Methods: A full class review of LMWH's was conducted in September of 2007 resulting in dalteparin replacing enoxaparin as the LMWH of choice. The Pharmacy and Therapeutics Committee approved automatic substitution with notification of the prescribing physician. The one exception to the policy was conversion if the patient was on enoxaparin at home, the policy would allow for continuation of therapy. Once the policy was approved, laminated dosing conversion cards and pre-printed order sets were developed. Multiple in-services were held prior to the official conversion date of October 15, 2007, to address any issues and to facilitate the conversion. Cost comparisons were made within individual settings adjusting for utilization levels. Results: In the fiscal year prior to the conversion from enoxaparin to dalteparin the cancer center purchased nearly $360,000 of enoxaparin for the inpatient and infusion center settings. In the year following the LMWH change, the total projected cost for LMWHs is $244,000, resulting in a 32% cost savings of $115,000. Conclusions: The change from enoxaparin to dalteparin resulted in significant cost savings for the cancer center. Additional studies are underway to examine the clinical outcomes of the LMWH change.

No significant financial relationships to disclose.
Why are patients lost to follow-up in a gynecologic oncology clinic?
Authors: Garcia V. C. , Manalo A. M. , Toral J. B. , Siasu M. L.
Published: August 2020

e17571

Background: The aim of this study is to investigate why patients are lost to follow-up in a gynecologic oncology clinic. Methods: Patients who had been lost to follow up previously, and eventually followed up between April and August 2007 were given a consent form and questionnaire to answer. An approximately equal number of patients who were not lost to follow-up were given the same questionnaire as controls. The first part of the questionnaire included the age, marital status, location, diagnosis/type of gynecologic cancer, type of intervention, educational attainment, occupation and monthly income. The second part asked directly the reason why they were lost to follow-up. Data were recorded in a computerized database via Microsoft Excel. Descriptive statistics were presented in mean, median, standard deviation, minimum, maximum and frequencies. Differences between patients who failed to follow-up (LF) and their controls (NLF) with respect to demographics, disease and treatment characteristics were assessed by an x2 test or independent t test, depending on the variable. SPSS version 15 was used to perform all analyses. A p < 0.05 was considered significant. Results: There were 50 patients who were not lost and 52 patients who were lost to follow-up. The demographic characteristics between these two groups; i.e., age, marital status, location, diagnosis/type of gynecologic cancer, type of intervention, educational attainment, occupation, and monthly income of patients were all not statistically significant. The most common reason why patients were lost to follow-up was they had no money. Other reasons included: symptoms became better or problems resolved, the follow up was at an inconvenient time and I had family commitment. Conclusions: Patients expressed that the main reason for not following-up was the lack of funds. The majority in these respondents lived below the minimum salary wages.

No significant financial relationships to disclose.
Video linked medical oncology clinics: A novel way to improve patients’ access to medical oncology services in rural Australia
Authors: Marr I. , Sabesan S.
Published: August 2020

e17573

Background: To improve the access of Mt Isa patients to medical oncologists, Townsville Cancer Centre runs weekly medical oncology clinics via videolink. Aim of this study was to assess patient satisfaction, safety of chemotherapy delivery, and cost effectiveness of such technology. Methods: Between 2006 and 2008, 42 patients were seen. A questionnaire based survey was conducted by telephone to assess patient's level of satisfaction and quality of communication. Safety of chemotherapy delivery was evaluated by retrospective chart audit. Results: 25 patients completed the questionnaire. Six were new patients and the rest were for review leading to more than 90 encounters. Satisfaction: 100% of those interviewed were satisfied with the care given by the Townsville Cancer Centre. Of these 88% felt they developed a friendly relationship with the specialist. 90% felt medication could be taken without any concerns after videolink. 27% of patients interviewed felt examination was needed by the specialist, but 92% of the patients would rather see the specialist via videolink than travel to Townsville. Overall 96% felt it saved time, money and was convenient. Responses, apart from the question about the need for physical examination by the specialist, were more than 80% in agreement. Safety: 32 patients received active therapy. 60% were treated with palliative intent and the rest adjuvant. The median number of cycles was 5 (1–8). A total of 4 patients were admitted for complications- 2 for febrile neutropenia and 2 for emesis.There were no treatment related deaths. Cost effectiveness: Factors for consideration were cost of patient and specialist travel and accommodation,cost of interruption of routine clinics at specialists’ home, cost of video link apparatus and maintenance and cost of disturbance of quality of life for patients and doctors resulting from travel. Conclusions: Satisfaction with video linked clinics is high. It saves travel time for the patients and specialists and seems to be cost effective. It is safe to supervise chemotherapy administration using this technology. Therefore, this method of service delivery could be adopted by medical oncology departments to improve services to the rural and remote areas.

No significant financial relationships to disclose.
A medical decision tree for the prophylaxis (P) and treatment (T) of tumor lysis syndrome (TLS): An international TLS consensus panel
Authors: Goldman S. , Coiffier B. , Reiter A. , Younes A. , Cairo M. S. ,   on behalf of the International TLS Expert Panel
Published: August 2020

e17575

Background: We (MC) previously established a definition of laboratory (LTLS) and clinical TLS (CTLS) and associated grading system (Cairo et al, BJH. 2004). Additionally, we recently reported an evidence based review of guidelines for the P and T of TLS (Coiffier et al, J Clin Oncol. 2008). Rasburicase (R), a recombinant urate oxidase, results in a more rapid and total reduction of uric acid (UA) compared to allopurinol (A) in children at high-risk of TLS (Goldman/Cairo et al, Blood. 2001) and a rapid reduction in UA in adults at high-risk of TLS (Coiffier et al, J Clin Oncol. 2003). It still remains to be determined which patients at risk of developing TLS should receive R versus A as initial TLS prophylaxis. Methods: We convened an international panel (N = 17) of experts in pediatric and adult hematological malignancies and solid tumors (ST) to develop a medical decision tree for the P and T of TLS based on the risk classification (low, medium, high) and management recommendations of Coiffier et al (J Clin Oncol. 2008) Results: Patients without evidence of LTLS were assigned to either low-risk disease (LRD), medium-risk (MRD), or high-risk (HRD). Risk factors included pathological classification stage, bulk, disease burden (WBC/LDH) and renal impairment/involvement. HRD was assigned to patients with either B-ALL, ALL/AML ≥100K/mm3, BL/LL stage III/IV, and/or high LDH, DLBCL/PTCL/MCL/ATL with bulky and elevated LDH and patients with MRD with renal impairment/involvement. MRD consisted of ALL ≤100K/mm3, AML 25–100K/mm3, BL/LL stage I/II and low LDH, childhood ALCL, DLBCL/PTCL/MCL/ATL non-bulky but elevated LDH, CLL treated with targeted therapy, and LRD with renal impairment/involvement. LRD consisted of ST (except bulky sensitive to cytotoxic therapy [MRD]), CML, MM, HL, other NHL and AML <25K/mm3. Conclusions: This medical decision tree will facilitate the practice of management of the P and T of TLS and hopefully improve the quality of care in a cost effective manner. *all authors have equal authorship and contribution

[Table: see text]
Concomitant pemetrexed/carboplatin chemotherapy with 3-D conformal radiotherapy followed by pemetrexed/carboplatin consolidation chemotherapy in locally advanced non-small cell lung cancer in a Chinese population
Authors: Ma S. , Xu Y. , Yu X.
Published: August 2020

e18502

Background: Pemetrexed in combination with carboplatin has been shown to have promising activity, as well as superior toxicity profile in advanced non-small cell lung cancer(NSCLC). Radiotherapy(RT) has been shown to improve survival of patients with locally advanced NSCLC when combined with other platin doublets. This phase II study of concomitant pemetrexed/carboplatin chemotherapy(CT) with 3-D conformal RT followed by pemetrexed/carboplatin consolidation CT in locally advanced NSCLC was designed to evaluate the efficacy and safety of this novel regimen. This report presents preliminary information of 10 patients who have completed treatment. Methods: 10 chemoradiation (CRT)-naive and stage IIIA or IIIB (not effusion) with KPS≥80 patients were included in this study between February 2008 and October 2008. Patients received pemetrexed 500 mg/m2, carboplatin AUC 5 CT repeated q3 weeks for 2 cycles concomitant with RT and 3 cycles of consolidation pemetrexed (500 mg/m2) and carboplatin (AUC=5) q3 weeks. Median total dose of RT, without elective nodal irradiation, was 62 Gy (range: 60-66 Gy) with 2 Gy daily fractions. Results: 1 (10%) and 8 patients (80%) had a complete or partial response respectively, while 1 patient(10%) had progression of the disease(brain metastases). The overall response rate (90%,95% confidence interval (CI): 68%-97%) exceeded the goal per study design. After concomitant CRT, the main toxicity was neutropenia, with a median ANC nadir of 1.6, three patients had Grade 3 neutropenia, One patient had Grade 4 neutropenia. Grade 3 thrombocytopenia was seen in one patient, grade 3 esophagitis in one patient and grade 3 radiation pneumonitis in one patient. Consolidation CT was not administered to 3 patients- one due to the development of brain metastases during the first month after chemoradiation, one due to patient refusal and one due to grade 3 radiation pneumonitis. Conclusions: This preliminary data suggests that concomitant treatment was well tolerated, with promising activity and a significant improvement of QoL in a Chinese population with locally advanced NSCLC.

No significant financial relationships to disclose.
Cisplatin and docetaxel plus concurrent three-dimensional (3D) conformal radiotherapy in unresectable stage III A/B NSCLC
Authors: Arcangeli L. , Orlandini B. , Torre M. , Carbonini C. , Sbarufatti A. , Vattemi E.
Published: August 2020

e18503

Background: Concurrent chemoradiation is standard of care for most patients with unresectable stage III A/B NSCLC but no standard chemotherapy regimen/schedule has been established. We conducted an experience to evaluate the efficacy and toxicity of a combination consisting of weekly docetaxel/cisplatin and radiotherapy in patients with unresectable stage III A/B NSCLC. Methods: Unresectable stage III A/B NSCLC pts with a good performance status (ECOG PS 0–1) were eligible. Patients with stage IIIB were chemonaive, while patients with stage IIIA were inoperable after a first line platinum-based chemotherapy. Treatment consisted of docetaxel 25 mg/m2 IV infusion followed by cisplatin 25 mg/m2 IV infusion was administered weekly during concurrent thoracic radiotherapy. Concurrent 3D-conformal RT thoracic radiation consisted of 45 Gy (1.8 Gy fractions 5 days/wk for first five weeks. Results: From 2006/01 to 2008/04, 16 pts were enrolled and all were evaluable for toxicity and response. Pt. characteristics: median age- 68 years (54–77), 80% males. Nine pts had stage IIIA (56%) and 7 patients had stage IIIB (44%).Histology subtypes included epidermoid (25%) and adenocarcinoma (75%). Radiologic response was seen in 11 patients (68%). Four patients had a stable disease (25%). Disease progression has occurred in 1 pt. Six patients undergone surgery after chemo-radiotherapy (37%). Four patients (25%) underwent a radical resection without residual mediastinal malignant disease. Toxicity was mild. Conclusions: Weekly docetaxel/cisplatin with concurrent 3D-conformal RT thoracic radiation plus is a well-tolerated out-patient regimen. and is feasible by multi-physicians collaboration group.

No significant financial relationships to disclose.
Radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent radiotherapy and gemcitabine after induction with gemcitabine and carboplatin
Authors: Michel R. M. , Gallardo-Rincon D. , Villarreal-Garza C. , Astorga-Ramos A. , Zamora J. , Martinez-Barrera L. , de la Garza J. , Arrieta O.
Published: August 2020

e18504

Background: The combination of chemotherapy (CT) and thoracic radiation (RT) is the standard treatment for locally advanced non-small cell lung cancer (NSCLC). The most favorable CT regime, timing of full-dose CT and the best way to combine CT with RT to maximize systemic and radiosensitizing effects remain to be determined. The aim of this study was to assess the efficacy, safety and tolerability of gemcitabine concurrent with RT after induction CT (gemcitabine + carboplatin) in locally advanced NSCLC. Methods: Patients with histologically proven NSCLC IIIA and IIIB received carboplatin (AUC of 2.5) and gemcitabine (800 mg/m2) on day 1 and 8, every 21 days (two cycles), followed by conventional fractioned RT (60Gy) with concomitant weekly gemcitabine 200 mg/m2 and by consolidation CT. Survival was analyzed with Kaplan-Meier. Results: Median follow-up was of 11.9 months, 11 patients (57.9%) had stage IIIB disease. Patient inclusion was discontinued due to high grade 3/4 radiation pneumonitis events (5/19 patients, 26.3%). One treatment-related death from radiation pneumonitis occurred. The most common hematological side effects grade 3/4 were anemia and neutropenia 3/19 (15.8%) each and thrombocytopenia 4/19 (21.1%) during induction CT. Partial response was observed in 11 patients (57.9%) following induction. After concurrent chemo-radiotherapy, overall response was 68.4%. Four patients underwent surgical resection. Median progression-free survival was 12 ± 1 months (95% CI, 9.8 -14.1). Overall survival was of 21 ± 3.5 months (95% CI, 14–27.9). Conclusions: Concurrent RT with gemcitabine after induction CT with gemcitabine and carboplatin showed a high response rate. However, it is associated with excessive pulmonary toxicity. Adjustments in gemcitabine dosage during RT or changes in RT planning could reduce toxicity.

No significant financial relationships to disclose.
Response and survival in African American (AA) patients (pts) with non-small cell lung cancer (NSCLC) treated with erlotinib (E)
Authors: Villaflor V. M. , Kanteti R. , Watson S. M. , Karrison T. , Vokes E. E. , Salgia R.
Published: August 2020

e19006

Background: Pts who respond to the EGFR- tyrosine kinase inhibitors (TKI's) frequently have activating mutations in the kinase domain of EGFR or EGFR overexpression. EGFR activating mutations correlate with adenocarcinoma histology, non-smoking history, female gender, and Asian ethnicity. The presence of EGFR kinase domain mutations is predictive of response but, the relationship is not always concordant. Furthermore, mutations may not predict survival benefit with TKI therapy and other factors are likely involved. It has also been determined that EGFR and met can crosstalk, and serve as potential mechanism of resistance in NSCLC. Most data collected to date on response and overall survival with EGFR-TKI's have been in the Caucasian or Asian community. Hence we collected data specific to the AA pt as they tend to have worse outcomes stage for stage. The purpose of this study is to report the response rate, overall survival, progression free survival (PFS) and clinical characteristics of AA pts with NSCLC treated with an EGFR-TKI. We will correlate these data with EGFR mutation and c-Met expression/mutations/amplifications for markers of NSCLC. Methods: We have listed patients with NSCLC receiving E therapy over the past 5 years. We then retrospectively collected demographic data (age, race, sex, and tobacco history), tumor histology, response rates, survival data and duration of response from AA pts treated with E as single agent. The response to E was correlated with outcome. Results: Data from 44 AA pts (27 women, 17 men) on erlotinib were reviewed. Mean age was 67.1 years (range 48–89 yrs), tobacco use (37 positive, 3 negative, and 4 not recorded). Histology included NSCLC not specified-14, squamous cell- 16, adenocarcinoma-11, large cell-1 and 2 not available. Overall response rate of 13.6% (6-PR, 16-SD, 18-progessive disease, and 4 patients lost to follow up). The PFS was 4.0 months; 95% CI: (2.5–6.6 mos) and overall survival 8.6 mos; 95% CI: (7.2–30.9 mos). EGFR mutations and c-Met analysis will be provided by ASCO meeting in May 2009. Conclusions: AA survival and response rates appear similar to previous data seen with all NSCLC patients receiving treatment with EGFR-TKI's. More data and relationship to biomarkers is needed in this population.

[Table: see text]
Adverse effects and associated costs with second- and third-line therapies for non-small cell lung cancer
Authors: Ye X. , Darkow T. , Reyes C.
Published: August 2020

e19009

Background: Chemotherapies used in the treatment of non-small cell lung cancer (NSCLC) are associated with a number of adverse effects (AEs), which may increase health care use and costs as patients receive treatment for these AEs.The objectives of this study were to compare occurrence of selected AEs and associated costs among patients receiving docetaxel (D), erlotinib (E), or pemetrexed (P) monotherapy as 2nd- or 3rd-line treatment of NSCLC in a retrospective claims database. Methods: Commercial enrollees with evidence of lung cancer were identified using ICD-9-CM diagnosis codes between 6/2004 and 12/2006. Pharmacy and medical claims were used to identify patients who received D, E, or P monotherapy as 2nd- or 3rd-line treatment. AEs were identified based upon diagnosis, procedure and prescription codes. Costs were compared between cohorts on a per month basis due to variable follow-up time. Results: Of 679 patients receiving 2nd-line treatment, 110 received D, 145 received E, and 116 received P. The most frequent AE was nausea/vomiting (N/V), which occurred in 90% of study subjects. Anemia (64%), neutropenia (35%), dyspnea (34%), and other respiratory AEs (35%) were also common. Compared with D, E was associated with significantly lower rates of neutropenia (3% vs. 46%; p < 0.0001), N/V (60% vs. 100%; p < 0.0001), and dehydration (10% vs. 20%; p = 0.03). P was also associated with higher rates of neutropenia and N/V than E (22% and 97%, respectively; p < 0.0001), as well as having a higher occurrence of anemia (74% vs. 49%; p < 0.0001). Costs to manage these AEs were also lower for E, with total costs related to AEs of $1494 for E, compared with $4386 for D (p = 0.004) and $6317 for P (p < 0.0001). Of 335 patients receiving 3rd-line treatment, 33 received D, 79 received E, and 80 received P. At least one AE was experienced by all patients in the D and P cohorts, while 73 (92%) E patients experienced at least one AE (p = 0.10 vs. D; p = 0.01 vs. P). Costs to manage AEs in the 3rd-line setting were lower for E ($2765) than for P ($4718; p = 0.02), while costs for E and D ($3680) were not significantly different (p = 0.28). Conclusions: Overall, occurrence of AEs commonly associated with 2nd- and 3rd-line agents for NSCLC was less frequent and less costly among E users.

[Table: see text]
Association of plasma EGFR mutations with response to first-line chemotherapy and prognosis in Chinese patients with advanced non-small cell lung cancer
Authors: Wu M. N. , Zhao J. , Bai H. , Zhuo M. L. , Wang S. H. , Yang L. , An T. T. , Wang X. , Duan J. C. , Wang Y. Y. , Wang J.
Published: August 2020

e19017

Background: To investigate associations of plasma EGFR mutations of advanced non-small cell lung cancer (NSCLC) patients with response to the first-line chemotherapy and prognosis. Methods: Plasma EGFR mutations from 145 chemotherapy-naive patients with advanced or metastatic NSCLC were examined by using denaturing high- performance liquid chromatography (DHPLC), and associations of EGFR mutations with tumor response to chemotherapy and clinical outcomes were evaluated. Results: 37.2% (54/145) of the patients was detected to have EGFR mutations in their plasma DNA. The response rate of mutated EGFR carriers to the chemotherapy was 37% (20/54), similar to that of 31.9% (29/91) of wild-type EGFR carriers to the chemotherapy (P= 0.323). Stage IV NSCLC patients with mutated EGFR had a longer PFS than those with wild-type EGFR (4 vs 3 months, P=0.043) after the first-line chemotherapy. The median survival time and 1-, 2- year survival rate for the patients with EGFR mutations (24 months and 85.7%,43.7%) were increased than those with wild-type EGFR (18 months and 65.7%,25.9%) (p=0.0468). Cox multivariate regression analysis showed that clinical stage (IV vs IIIb), response to the first-line chemotherapy (PR vs PD), and EGFR mutations were independent prognostic factors (P=0.008, 0.000 and 0.000 respectively). Conclusions: We conclude that plasma EGFR mutations in the Chinese patients with advanced NSCLC were not associated with response to the first-line chemotherapy, but Stage IV NSCLC patients with mutated EGFR had a longer PFS after the chemotherapy.

No significant financial relationships to disclose.
Results of 27 years of phase III trials for patients with extensive-disease small-cell lung cancer
Authors: Oze I. , Kiura K. , Hotta K. , Ochi N. , Fujiwara Y. , Takigawa N. , Tabata M. , Shinkai T. , Tanimoto M.
Published: August 2020

e19021

Background: Few studies have formally assessed whether treatment outcomes for patients with extensive-disease small-cell lung cancer (ED-SCLC) enrolled in Phase III trials have improved substantially over the years. This investigation determined the trends in the outcomes for the patients in those trials. Methods: We analyzed trials that were reported between January 1991 and August 2008. Phase III randomized controlled trials were eligible if they compared first-line, systemic chemotherapy for ED-SCLC. Data were evaluated using linear regression analysis. Results: We identified 55 trials initiated between 1980 and 2006, involving 10,407 patients with 116 chemotherapy arms. The number of randomized patients and the proportions of patients with good performance status (PS) increased with the passage of time. In the 1990s, increasing numbers of studies examined cisplatin-based regimens, especially cisplatin and etoposide (PE) regimens, while decreasing numbers examined cyclophosphamide, doxorubicin, and vincristine-based regimens. A scattergram of the parameters ‘year of trial initiation’ and ‘median survival time’ (MST) indicated that MST increased 0.024 months (0.71 days) per year (P = 0.198). The multiple regression analysis showed no significant survival improvement over the years (regression coefficient for the year of trial initiation = 0.004, P = 0.980). In addition, the use of PE regimens did not prolong survival, whilst the proportion of good PS patients and the assignment of prophylactic cranial irradiation were significantly associated with favorable outcomes. Conclusions: The survival of patients with ED-SCLC enrolled in phase III trials has not improved significantly over the years, suggesting the need for a breakthrough, such as the discovery of novel molecular targets.

No significant financial relationships to disclose.
Phase II study of bevacizumab in combination with cisplatin and docetaxel as first-line treatment of patients (p) with metastatic non-squamous non-small cell lung cancer (NSCLC)
Authors: Ferrer N. , Cobo M. , Paredes A. , Méndez M. , Muñoz-Langa J. , Rueda A. , Álvarez de Mon M. , Sánchez-Hernández A. , Gallego R. , Torrego J.
Published: August 2020

e19023

Background: Bevacizumab (B), in addition to platinum-based chemotherapy, is indicated for 1st-line treatment of p with advanced NSCLC other than predominantly squamous cell histology. B has been shown to improve progression free survival (PFS) and overall survival (OS) when combined with cisplatin/gemcitabine and carboplatin/paclitaxel, respectively. However, there are limited data on the safety and efficacy of B in combination with other widely used chemotherapy doublets for NSCLC. This is a single-arm, open- labeled, single-stage phase II trial of cisplatin (C), docetaxel (D) and B for NSCLC. Methods: Eligibility criteria: chemo- naïve, stage IIIB wet or IV, non-squamous NSCLC, PS 0–1, no brain metastases and no history of gross hemoptysis. P received D (75 mg/m2), C (75 mg/m2), and B (15 mg/kg iv) on day 1 every 3 weeks for up to 6 cycles, followed by B 15 mg/kg alone every 3 weeks until disease progression or toxicity. Primary endpoint: PFS. Results: 50 p were enrolled (enrollment completed): 24% female, median age 60 (36–74), PS 1: 64%, adenocarcinoma: 72%; stage IV: 92%. Two p did not start treatment. Median follow-up is 5.3 months (range 0–13.6). Median number of cycles of B was 7 (range 0–18). 56% completed 6 cycles of treatment; 24% received ≥ 12 cycles of B. Most frequent grade ≥ 3 toxicities: diarrhea (14.6%), fatigue (14.6%), dyspnea (9.8%), anorexia (4.9%), alopecia (4.9%), esophagitis (4.9%), constipation (4.9%), mucositis (12.2%), proteinuria (4.9%); hematological toxicities: neutropenia (22%), febrile neutropenia (9.8%), leucopenia (14.6%), lymphopenia (4.9%). Of interest, 41.5% developed grade <3 epistaxis and 17% hypertension (1 p grade 3). One p died due to hemoptysis. 46 p were evaluable for response: 29 PRs (ORR: 63%). 18 of 48 p have experienced progression or death with a median SLP of 7.8 months (95% CI: 6.6-NR). Median OS is 13.5 months (95% CI: 12.7–13.6; 81.2% p censored); 1-year survival is 83.9% (95% CI: 67.4%-92.5%). Conclusions: Treatment with C, D and B, followed by maintenance B in 1st line of advanced non-squamous NSCLC shows an acceptable toxicity profile and promising efficacy. Final results will be presented.

[Table: see text]
A phase II trial of combination chemotherapy with irinotecan and amrubicin in pretreated patients with non-small cell lung cancer (NSCLC): Results of Okayama Lung Cancer Study Group Trial 0402
Authors: Kuyama S. , Segawa Y. , Nogami N. , Kiura K. , Takigawa N. , Shibayama T. , Hosokawa S. , Aoe K. , Tabata M. , Tanimoto M. ,   Okayama Lung Cancer Study Group
Published: August 2020

e19029

Background: We previously conducted a phase I trial of combination chemotherapy with irinotecan and amrubicin for NSCLC and found acceptable toxicity profiles with a favorable efficacy in patients with pretreated NSCLC. The aim of this phase II trial was to further evaluate its efficacy and toxicity in this population with a long-term follow-up. Methods: Primary endpoint was objective response. Patients with NSCLC previously treated with one or two chemotherapy regimens were enrolled in this trial. Irinotecan and amrubicin were both administered on days 1 and 8, every 3 weeks at doses of 100 and 40 mg/m2, respectively. Response and toxicity were assessed according to the RECIST guideline and NCI-CTC for AE v3.0. Results: Thirty-one pretreated NSCLC patients were enrolled between 2004 and 2006. A median number of courses administered was 3 (range: 1 to 6). All patients and courses were assessable for efficacy and safety. Demographics of the patients were as follows: M/F:21/10, Ad/others:21/10, ECOG-PS 0/1:12/19, and smoker/non-smoker:21/10. Platinum-based regimens were commonly used as the prior chemotherapy. Objective response was obtained in 9 of the 31 patients with a response rate of 29.0% (95%CI: 12.1–46.0%). Grade 4 leukopenia and neutropenia were observed in 6 (19%) and 14 (45%) patients, respectively, whereas thrombocytopenia were generally mild. Grade 3 febrile neutropenia was observed in 7 patients (23%), of whom two patients further developed Grade 4 and 5 septic shock each. Other grade 3 or greater non-hematological toxicities included diarrhea, vomiting, pneumonitis, liver dysfunction in 4, 1, 1 and 2 patients, respectively. With a median follow-up time of 24.2 months, median survival time and median progression-free survival time were 14.2 and 4.0 months, respectively. Conclusions: This combination seemed highly effective for pretreated NSCLC with an acceptable toxicity.

No significant financial relationships to disclose.
Paclitaxel versus oral vinorelbine in patients with advanced non-small cell lung cancer (NSCLC) with performance status (PS) 2: A randomized phase II study
Authors: Syrigos K. N. , Bacoyiannis C. , Makatsoris T. , Bamias A. , Klouvas G. , Nicolaides C. , Boukovinas I. , Linardou E. , Fountzilas G. , Kosmidis P.
Published: August 2020

e19035

Background: The optimal treatment of patients with advanced NSCLC and PS 2 is not well established. Our group has shown that single agent is equally effective to doublets. Purpose of this study was to compare efficacy and toxicity of two single agents Paclitaxel and oral Vinorelbine. Methods: 75 stage IIIb wet and IV chemotherapy-naïve for metastatic disease patients with PS 2 were randomized to either Paclitaxel 90mg/m2 weekly (group A: 36pts) or Vinorelbine 60mg/m2 weekly (group B: 34pts). Both agents were given for three weeks on and one week off. Results: A total of 70 out of 75 patients were eligible for analysis. All patient and disease characteristics were well balanced. Partial response rate (PR) was 14% (95% CI, 4.7%-29.5%) and 6% (95% CI, 0.7%- 19.7%) for groups A and B respectively. Stable disease (SD) was 17% (95% CI, 6.4%-32.8%) and 12% (95% CI, 3.3%-27.5%) respectively. These rates did not differ significantly. Median survival (OS) was 5.3m (95% CI, 3.1–7.5 m) and 3.5m (95% CI, 1.6 - 5.4 m) respectively (P=0.6). Progression free survival (PFS) was 3.2m (95% CI, 1.9 - 4.6 m) and 2.1m (95% CI, 1.8 - 2.3 m) respectively (P=0.2). There was a non-statistically significant trend for more myelotoxicity in the vinorelbine group. Conclusions: A trend for higher efficacy and less toxicity of Paclitaxel in comparison to oral Vinorelbine was observed, without however reaching statistical significance.

No significant financial relationships to disclose.
Distribution of metastases in NSCLC: Economic impact of imaging
Authors: Pineda C. , Cadogan K. V. , Cadogan M. A.
Published: August 2020

e19036

Background: Purpose: to investigate the usefulness and cost-effectiveness of routine pelvic CT scans in patients with NSCLC. Given that many patients have metastases to several organs, one important question is - “what is the frequency of metastases in the chest, the abdomen, the pelvis, elsewhere?” Methods: We retrospectively reviewed the CT data of 184 patients with Stage 4 NSCLC. The results are shown in Table 1 . Results: We found that there were 690 metastases to the chest, 205 to the abdomen, 80 to the bones, 18 to the pelvis, 13 to the brain and 23 others, not specified. These represent a relative incidence of 67%, 20%, 8%, 2%, 1% and 2%, respectively. These results are a strong indicator of the main areas that require imaging in NSCLC. If we consider the actual incidence of metastases, we find the following absolute statistics: 16 patients had pelvic involvement. This compares with 42 patients with adrenal metastases, 81 with liver metastases, 80 with bone metastases, 112 with hilar adenopathy, and 159 with mediastinal adenopathy. (See Table ) Conclusions: The cost of a CT of the pelvis varies, but is estimated at approximately $2000[Fred, Herbert L., MD, MACP. Drawbacks and Limitations of Computed Tomography: Views from a Medical Educator. Texas Heart Institute Journal 31 (2004): 345.]. The incidence of NSCLC is approximately 172,000 in 2008[Ries, LAG, et al (eds). SEER Cancer Statistics Review, 1975–2005. Surveillance Epidemiology and End Results. 2007. National Cancer Institute. 03JAN2009. http://seer.cancer.gov/csr/1975_2005/ .]. Hence, the potential annual savings accrued by not performing CT of the pelvis is approximately $344 million. These costs can be justified in a Research setting, but it is more difficult to do so in the clinical arena.

[Table: see text]

No significant financial relationships to disclose.
A phase II trial of adding cetuximab to cisplatin and gemcitabine as first-line therapy in advanced non-small cell lung cancer (NSCLC)
Authors: Barata F. , Parente B. , Teixeira E. , Costa A. , Fernandes A. , Pimentel F. L. , Carvalho L.
Published: August 2020

e19043

Background: Phase II and III studies have demonstrated that the EGFR-antibody, cetuximab (Erbitux), improves efficacy parameters when added to a platinum-based chemotherapy in the 1st-line treatment of patients with advanced NSCLC. This study assessed the efficacy and tolerability of cetuximab in combination with cisplatin and gemcitabine in this setting. Methods: Patients in this multicenter, single-arm, phase II Portuguese study received cetuximab (400 mg/m2 initial dose then 250 mg/m2 weekly) in combination with cisplatin (40 mg/m2) and gemcitabine (1,200 mg/m2) for 6 cycles (21 days). Main eligibility criteria included metastatic NSCLC of any histological subtype, ECOG PS 0/1, and measurable disease. Patients with brain metastases were excluded. The primary endpoint was the overall response rate (ORR) during treatment, according to RECIST criteria. Secondary endpoints included time to progression (TTP), overall survival, and adverse events. Statistical analyses were performed for the intention to treat (ITT) and per protocol populations. ORRs and the corresponding 95% confidence intervals (CIs) were estimated and Kaplan-Meier curves were computed for TTP. Results: A total of 48 patients were enrolled between December 2006 and March 2008. Seventy five percent of the patients were men and the median age was 62.5 years (range 34–75). Median TTP was 5.0 months (95% CI 3.9–6.1 months). Best ORR were 35.4% (95% CI 22.2–50.5%) and 38.1% (95% CI 23.6–54.4%) for the ITT and PP populations, respectively. No differences in response rates were observed when EGFR status (as determined by FISH and immunohistochemistry) was taken into consideration. Ninety-six grade III/V adverse events were reported; the most common were neutropenia and thrombocytopenia (36 and 18 events, respectively). Conclusions: Adding cetuximab to cisplatin and gemcitabine demonstrated high efficacy (ORR and TTP) with acceptable toxicities in a nonselected population of patients in 1st-line treatment of NSCLC.

No significant financial relationships to disclose.
Safety and efficacy of AMG 655 in combination with paclitaxel and carboplatin (PC) in patients with advanced non-small cell lung cancer (NSCLC)
Authors: Paz-Ares L. , Sánchez Torres J. M. , Diaz-Padilla I. , Links M. , Reguart N. , Boyer M. , Wiezorek J. , Sabin T. , Pan Y. , Van Meerbeeck J.
Published: August 2020

e19048

Background: AMG 655 is an investigational, fully human IgG1 monoclonal agonist antibody that binds human death receptor 5 (DR5), activates caspases, and induces apoptosis in sensitive tumor cells. The primary objective of this phase 1b study was to determine the maximum tolerated dose (up to a target dose of 15 mg/kg) of AMG 655 that can be safely administered with PC. Methods: Eligibility included: ≥ 18-years old, untreated, advanced NSCLC, and ECOG PS 0 or 1. Patients (pts) were enrolled in sequential dose cohorts of AMG 655 (5 or 15 mg/kg) + P (200 mg/m2) and C (AUC = 6 mg/mL x min) IV every 3 weeks for up to 6 cycles. After completion/discontinuation of PC, pts may continue AMG 655 as monotherapy. Endpoints include: incidence of dose- limiting toxicities (DLT); adverse events (AE); pharmacokinetics (PK); levels of plasma genomic (g)DNA, serum caspase 3/7 activity, and M65 (cell death and apoptosis biomarkers); objective tumor response rate (by RECIST), and progression-free survival (PFS). Results: As of 09/08, 12 pts enrolled and received ≥ 1 dose of AMG 655 + PC. Ten were men; 11 had ECOG 1, and median (range) age = 68.5 (50–83) years. Median (range) time on AMG 655 = 5.2 (0.2–8.3) months; all pts have discontinued treatment. There was 1 DLT: grade 3 hyponatremia (15-mg/kg cohort). Five (42%) pts had grade 3 AE including neutropenia and dyspnea (2 pts each); 3 (25%) had grade 4 AE (2 with neutropenia, 1 with pulmonary embolism). After one 5- or 15-mg/kg dose of AMG 655 + PC, AMG 655 PK values (serum clearance, Cmax, AUC) were similar to the first-in-human study (LoRusso et al. JCO 2007; 25: abstr 3534) indicating no effect of PC on PK of AMG 655. Data also indicate no effect of AMG 655 on PK of PC. Plasma gDNA, serum caspse 3/7 activity, and serum M65 levels increased significantly from baseline 24 h after administration of AMG 655 + PC. Best overall tumor response: 1 complete response, 3 partial responses, 3 stable disease, and 3 progressive disease (2 pts had no on-treatment tumor assessments). Median (95% CI) PFS = 5.1 months (1.5, 7.0). Conclusions: AMG 655 administered with PC appears to be well tolerated with expected PK properties not altered by PC. A randomized phase 2 trial (AMG 655 ± PC) is ongoing.

[Table: see text]
Chemosensitivity of newly established human malignant pleural mesothelioma cells: Significant growth inhibition by amrubicin, a novel 9-aminoanthracycline, or cyclooxygenase 2 inhibitor
Authors: Hida T. , Ogawa S. , Park J. , Park J. , Shimizu J. , Horio Y. , Yoshida K. , Sekido Y.
Published: August 2020

e19060

Background: Malignant pleural mesothelioma is asbestos-related malignancy that is highly resistant to current therapeutic modalities. Survival of patients with malignant mesothelioma is very poor, especially in advanced stage, regardless of a recent advancement of chemotherapeutical modalities of combination with cisplatin and antifolate. Methods: Eleven cell lines derived from malignant mesothelioma were established in our laboratory. Chemosensitivity of these cell lines to nine chemotherapeutic drugs (cisplatin, vinorelbine, irinotecan, gemcitabine, pemetrexed, gefitinib, erlotinib, and amrubicin and its active in vivo substance, amrubicin-13-OH) and four cyclooxygenase 2 inhibitors was tested by MTT assay. Results: Anti-cancer agents, cisplatin, vinorelbine, gemcitabine, gefitinib, or erlotinib, showed little growth inhibition, and pemetrexed and irinotecan showed modest growth inhibition in malignant mesothelioma cells, whereas amrubicin-13-OH showed strong growth inhibition. Cyclooxygenase 2 inhibitors inhibit proliferation of malignant mesothelioma cells in a dose-dependent manner: modest growth inhibition at clinically achievable low concentrations and complete growth inhibition at clinically achievable high concentrations by intrapleural instillation. In addition, enhanced growth suppression was obtained by using amrubicin-13-OH in combination with cyclooxygenase 2 inhibitor. Conclusions: Our study suggests that amrubicin can inhibit proliferation of malignant mesothelioma cells. In addition, the use of a cyclooxygenase 2 inhibitor may be a promising therapeutic approach in the treatment of mesothelioma, because previous studies indicated the presence of increased cyclooxygenase 2 expression in malignant mesothelioma, which is notoriously resistant to chemotherapy.

No significant financial relationships to disclose.