Months Of Median Time Research Articles

Prolonged Use of Eltrombopag in Patients with Severe Aplastic Anemia without Complete Response at 6 Months after Immunosuppressive Therapy

Background Eltrombopag (EPAG) could improve the efficacy of immunosuppressive therapy (IST) consisted by antithymocyte immunoglobulin (ATG) and cyclosporin (CsA) in untreated severe aplastic anemia (SAA) patients. This study explored whether patients with SAA could benefit from continuous use of EPAG beyond 6 months. Methods From February 2018 to October 2021, 92 Chinese patients who were 2 years of age or older with a new diagnosis of acquired SAA and were not eligible for front-line hematopoietic stem-cell transplantation were collected in the China Eastern Cooperation Group for Anemia (CECGA). Patients were treated with rabbit ATG (r-ATG) based IST consisting of CsA. Patients over 12 years old and aging 6-11 years old took EPAG orally at dose of 75mg and 37.5mg once daily, respectively; EPAG was administered with 1.25 mg per kilogram per day for patients with age distribution between 2 and 5 years. Generally, all patients were treated with EPAG at least 6 months. The lack of response at 6 months, relapse, HSCT, development of a clonal hematologic disease including myelodysplastic syndrome, and acute myelogenous leukemia, or disease- or treatment-related death are regarded as events in event free survival (EFS). Results The median age was 38 (2-78) years, with 18 patients (20%) under 18 years old and 21 patients (43%) over 60 years old. In the whole cohort, 61 patients (66%) were diagnosed as SAA and 31 patients (34%) with very severe aplastic anemia (vSAA). At 3, 6 and 12 months, the actuarial overall response rates (ORR) were 55% (51 of 92), 73% (67 of 92) and 81% (60 of 74) and complete response (CR) rates were 11% (10 of 92), 20% (18 of 92) and 34% (25 of 74), respectively. 18 patients (20%) who achieved CR within 6 months were under steady state. In 49 patients with PR at 6 months, 14 (35%) of 40 patients who were continuously exposed to EPAG improved to CR within 6.5 (3 ~ 10) months of median time after 6 months. Among 25 patients who failed at 6 months, 11 patients continued to use EPAG, and 5 patients (45%) improved responses with extended median time of 3 (1 ~ 6) months after 6 months (Figure 1). The cumulative effect curve showed that 93% and 58% of all 12 months remission and CR occurred within 6 months. In patients with PR and NR at 6 months, the better 2-year event free survival (EFS) was found in whom continued to use EPAG (75% vs. 26%, P=0.001) (Figure 2). Discussion EPAG plus IST were used to treat previously untreated SAA patients in prospective studies. The ORR and CR rate at 6 months were 68% ~ 94% and 26% ~ 58%, respectively [1, 2]. We found that 93% of all 12 months remission occurred within 6 months for patients treated with IST and EPAG. It is suggested that EPAG should be used in sufficient dosage at least 6 months. It has been reported that patients with CR and PR were present with better OS of 100% and 92%, while OS of non-responders was 47% (P=0.0016), effect was demonstrated as a predictor for 4-year OS [3]. For patients with PR and NR at 6 months in our study, it was found that not only the response rates, but also the 2-year EFS were improved by continuous usage of EPAG, compared to them discontinued EPAG. In conclusion, additional EPAG to IST mainly take effect within 6 months. Continuous administration of EPAG could improve the hematologic response and EFS in patients without achieving CR at 6 months. REFERENCE [1]. Townsley DM, Scheinberg P, Winkler T, et al., Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia. N Engl J Med, 2017. 376(16): p. 1540-1550. [2]. Peffault de Latour R, Kulasekararaj A, Iacobelli S, et al., Eltrombopag Added to Immunosuppression in Severe Aplastic Anemia. N Engl J Med, 2022. 386(1):11-23. [3]. Assi R, Garcia-Manero G, Ravandi F, et al., Addition of Eltrombopag to Immunosuppressive Therapy in Patients with Newly Diagnosed Aplastic Anemia. Cancer, 2018. 124(21):4192-4201. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Delays on Breast Cancer Treatment in Brazil: Implications on Survival

Background: Breast cancer survival may vary among regions in Brazil, being lower in northern and northeastern than in southern and southeastern regions. Earlier studies in developed countries have suggested that increased time intervals of care are associated with poorer chances for survival. There is a lack of studies on developing countries about the effect of time interval on survival. Aim: To estimate the effect of treatment delay on 3- and 5-years survival among women diagnosed with breast cancer treated on the National Cancer Institute in Rio de Janeiro, Brazil. Methods: A retrospective study on a cohort of 3220 women newly diagnosed with breast cancer between 2011 and 2013 was accomplished. Follow-up time was 60 months for women diagnosed in 2011-2012 (n=836), and 36 months for the whole cohort. Times from diagnose to treatment initiation were analyzed according to the Brazilian law for cancer patient treatment (< 60 > days). All data were obtained from hospital-based cancer registry and medical reports. Estimates of 3- and 5-survival were proceeded by Kaplan-Meier method. Survival curves differences were evaluated by 95% log-rank test. Crude and adjusted hazard ratios between delay on treatment initiation, age, education, stage and 1st treatment and death risk were estimated by proportional Cox regression with respective 95% confidential interval. Results: Mean time follow-up in the 2011-2012 cohort was 55.3 (± 12.7) months with median time of 60 months; while in the whole cohort mean follow-up time was 34.1 (± 6.1) months with 36 months of median time. Concerning the treatment delay, 3-years survival rates were 88.7% among women with ≤ 60 days for treatment initiation and 88% among women with delay on treatment (log-rank: 0.786); while 5-years survival rates were 85.2% among women with ≤ 60 days to treatment and 82.5% for women with delays on treatment (log-rank: 0.373). Delay on treatment (OR=0.77; 95 CI: 0.61-0.97), age ≥ 70 years old (OR=2.03; 95% CI: 1.46-2.82), late stage at diagnosis (OR=7.48; 95% CI: 2.27-24.61), and 1st treatment (ORCHEMO=2.66; 95% CI: 1.82-3.90; ORRADIATION/HORMONE=2.53; 95% CI: 1.58-4.06) were independently associated with death risk in 3 years. Death risk in 5 years is independently associated to age ≥ 70 years (OR=3.37; 95% CI: 1.89-6.00), chemotherapy as 1st treatment (OR=2.05; 95% CI: 1.04-4.03), and late stage (OR=11.14; 95% CI: 1.41-88.06). Conclusion: Delay on treatment initiation seems not influence 3- and 5-years survival rates in the studied population. However, after adjusted by age, stage, and treatment, delays on treatment initiation affected negatively the death risk in 3 years. On the other hand, 5-years death risk was independently associated with age ≥ 70 years, chemotherapy as 1st treatment, and late stage.

Percutaneous radiofrequency ablation for medically inoperable patients with clinical stage I non-small cell lung cancer.

BackgroundA retrospective evaluation of percutaneous radiofrequency ablation (RFA) in medically inoperable patients with clinical stage I non-small cell lung cancer (NSCLC).MethodsBetween 2008 and 2014, 29 medically inoperable patients with clinical stage I NSCLC underwent percutaneous RFA. We evaluated the feasibility, safety, and effectiveness.ResultsThere were 18 men and 11 women with a median age of 78.0 years (range 56–85), mean 76.0 years. No procedure-related deaths occurred in any of the 33 ablation procedures. The mean follow-up was 25 months. The incidence of local tumor progression was 21.0% at 25 months of median time to progression after the initial RFA. The mean overall survival (OS) was 57 months (95% confidence interval (CI) 44–70 months). The mean cancer-specific survival CSS was 63 months (95% CI 50–75 months). OS was 90.5% ± 6.4% at one year, 76.4% ± 10.7% at two, and 65.5% ± 13.6% at three years. CSS was 95.2% ± 4.6% at one, 86.6% ± 9.3% at two, and 74.2% ± 13.9% at three years in all patients. The survival for stage IA and IB cancers were 87.5% and 92.3% at one, 87.5% and 73.4% at two, and 87.5% and 58.7% at three years, respectively. Survival rates were not significantly different between the two groups (P = 0.596), with mean survival times of 65 (95% CI: 51–79 months) and 55 months (95% CI: 38–71 months), respectively.ConclusionPercutaneous RFA is a safe, feasible, and effective procedure in medically inoperable clinical stage I NSCLC patients.

Abiraterone acetate: a hat trick of clinical benefits

A substantial proportion of men with advanced prostate cancer develop bone metastases, which can lead to pronounced morbidity as a result of bone pain and skeletal-related events.1 Many newer drugs for metastatic castration-resistant prostate cancer, including abiraterone acetate, have a broad range of efficacy, which manifests as prolonged survival and improved quality of life. In The Lancet Oncology, Christopher Logothetis and colleagues2 report the outcomes related to pain and skeletal-related events from COU-AA-301, the placebo-controlled phase 3 trial that led the US Food and Drug Administration to approve abiraterone acetate for use in the postchemotherapy setting. The authors report that, in men with clinically significant pain scores at baseline, abiraterone acetate and prednisone led to palliation of pain in 157 of 349 patients (45·0%) compared with 47 of 163 (28·8%) given placebo and prednisone (p=0·0005); pain palliation was also achieved more quickly in patients given abiraterone acetate and prednisone (5·6 months vs 13·7 months, p=0·0018). A delay of 4·7 months in median time to first skeletal-related event was also noted in the abiraterone acetate plus prednisone group compared with the prednisone only group (HR 0·615, 95% CI 0·478–0·791; p=0·0001). These data show abiraterone acetate’s therapeutic versatility. Although it seems intuitive that drugs leading to improved overall survival in men with metastatic castration-resistant prostate cancer would also lead to improvements in pain and functionality, this has not always been the case. The most apparent example of a treatment with discordant survival and palliative effects is the autologous immunotherapy product sipuleucel-T.3 A range of new drugs that improve survival as well as quality of life are now available— including the chemotherapeutics docetaxel and cabazitaxel, the radiopharmaceutical radium-223, the novel androgen-signalling inhibitor enzalutamide, and abiraterone acetate2,4–8—and thus the bar has been raised in terms of choosing which drugs to prescribe. Survival alone might not be enough. Conversely, some drugs show clear palliative benefits but do not affect overall survival—eg, the osteoclast inhibitors denosumab and zoledronate, both of which help to prevent skeletal-related events (zoledronate also improves pain scores).9,10 It should be noted that, although the phase 3 trial comparing denosumab with zoledronate was not powered to specifically assess pain outcomes, pain events occurred at similar frequencies in both groups. On the basis of Logothetis and colleagues’ study, abiraterone acetate can join radium-223 and enzalutamide in improving both overall survival and skeletal-related events.2,6–8 Logothetis and colleagues’ study has several limitations. First, previous bisphosphonate use—a potentially confounding issue—was not controlled for. A multivariable analysis adjusting for previous or ongoing bisphosphonate use would be helpful to establish whether osteoclast inhibition could have accounted for some of the improvements in pain scores and skeletal-related events noted in the abiraterone acetate group. The median pain score of patients enrolled in COU-AA-301 was 3/10, with clinically significant pain defined as 4/10 or greater. Although this point might seem trivial (because only those with significant pain were included in the analysis of pain-related outcomes), it is not clear what the baseline characteristics were for patients who experienced a palliative benefit. We do not doubt that abiraterone acetate provides a palliative benefit and delays skeletal-related events. However, we would caution against a palliation and prevention strategy for skeletal-related events that relies exclusively on the drug. Although COU-AA-301 was not powered specifically to detect improvements in pain scores, several clinical trials have been designed with pain palliation endpoints in mind, such as a phase 3 study comparing cabozantinib with mitoxantrone hydrochloride in men with docetaxel-refractory metastatic castration-resistant prostate cancer ({type:clinical-trial,attrs:{text:NCT01522443,term_id:NCT01522443}}NCT01522443) and another assessing the anti-clusterin oligonucleotide custirsen plus a taxane in men with docetaxel-refractory disease ({type:clinical-trial,attrs:{text:NCT01083615,term_id:NCT01083615}}NCT01083615). Both trials have used pain responses as their primary endpoints—a clear acknowledgment that palliation probably deserves a more prominent role in future trial design. In summary, mounting evidence suggests that abiraterone acetate not only extends survival in patients with metastatic castration-resistant prostate cancer, but also improves pain and delays skeletal-related events, providing a hat trick of clinical benefits—ie, improving how long patients survive, feel, and function. The time has come for trials to be designed not only to establish survival improvements, but also to define the palliative role that newer drugs might have in the treatment of advanced prostate cancer.

An interim analysis of a phase II study of the combination of TACE and sorafenib in patients with unresectable hepatocellular carcinoma in National Cancer Center Korea (COTSUN KOREA, NCT00919009).

253 Background: Transarterial chemoembolization (TACE) is the palliative treatment for patients with unresectable HCC. TACE-induced ischemic injury is known to increase circulating VEGF and related with poor prognosis.The aim of this study is to evaluate efficacy and safety of combined TACE with sorafenib, VEGFR inhibitor in unresectable HCC patients. Methods: This study is a non-randomized, open-labeld, single-arm, phase II investigator-initiated clinical study. Estimated number of subjects was 50 under the assumption of 3.2 months of median time to progression (TTP) with TACE alone. All patients are Child-Pugh class A or superb B. Sorafenib begins to be administered on 3 days after the first session of TACE and will be subsequently administered up to 24 weeks. Efficacy of TACE was evaluated after 4 weeks from TACE by dynamic CT. Repeated TACE is performed “on demand” in case of PR or SD according to CT/MRI evaluation. Results: A total of 50 patients were enrolled for this interim analysis. Male was 84% and mean age was 61.5years. Causes of underlying chronic liver disease were HBV in 28 patients (65.1%). Patients were categorized into modified UICC stage II (15, 30.0%), III (24, 48.0%) and IVA (11, 22.0%). Median follow-up period was 5.3 months (range, 1.0–13.1). The size of index lesions was ranged from 1.0 cm to 13.1 cm, and number of lesions was between 1 and 5. Number of TACE sessions was 1.0 (range, 1–4). Common adverse events (AE) during sorafenib therapy were elevation of serum AST/ALT (96.8%), hypocalcemia (90.0%), thrombocytopenia (84.0%), and hyperbilirubinemia (76.0%). Hand-foot skin reaction was most frequently observed among AE of NCI CTCAE grade 3 or higher (40.0%), followed by elevation of serum ALT (38.0%). Dose reduction of sorafenib was needed most commonly due to hand-food skin reaction (n=29). Median TTP was 5.1 months (range, 3.8–6.3). Conclusions: Adverse events were approved as acceptable by independent monitoring system. Preliminary evidence of antitumor activity was also observed. This trial can be safely performed with close monitoring in inoperable and/or unresectable HCC patients. No significant financial relationships to disclose.

Expression of epidermal growth factor receptor and cyclin D1 in pretreatment biopsies as a predictive factor of radiotherapy efficacy in early glottic cancer

To evaluate the prognostic value of the expressions of epidermal growth factor receptor (EGFR) and cyclin D1 in early glottic cancer treated with radiotherapy only. One hundred fifty-one patients with T1-2, N0 glottic cancer who had been treated with radiotherapy at Seoul National University Hospital since 1992 through 2004. Immunohistochemical staining for EGFR and cyclin D1 were performed on the formalin-fixed paraffin-embedded tissues of 25 patients who developed local recurrence and on the tissues of 25 matched patients free from disease. Patterns and degrees of expression were compared between these 2 groups. High EGFR (p = .047) and high cyclin D1 (p = .040) expressions were both found to be significantly associated with a poor prognosis. No association was found between EGFR and cyclin D1 status (p = .158), but EGFR and cyclin D1 status in combination were found to be significantly associated with local control. The patients with both high EGFR and high cyclin D1 expression had the poorest outcome compared with the others (14 months vs 29 months of median time to progression). Patterns of EGFR and cyclin D1 expression changed after recurrence, but these changes were not found to alter the ultimate prognosis. The molecular biomarkers, EGFR and cyclin D1 have a prognostic significance in early glottic cancer. These markers in combination seem to play an important role in tumor relapse and may be useful for selecting patients with a poor outcome after radiotherapy.