There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to ...evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based).
A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and ≥ 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy.
The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0-14.0) months in the ET arm of group A, and 5.3 (3.9-6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8-7.7) months in the ET arm of group B, and 5.7 (4.6-6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5-8.0) months in the ET arm of group C and 4.0 (3.5-4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months.
Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET.
Abstract
Objectives:
Taxanes are standard for first-line chemotherapy of metastatic breast cancer (MBC), but indications for single-agent versus combination treatment remain controversial. This ...non-interventional study in 12 different countries explored treatment patterns and progression-free survival (PFS) in routine practice.
Research design and methods:
The prospective study was designed to determine factors associated with the choice of taxane-based regimens for MBC. Data were collected at the start of first-line treatment planned by the physician (baseline), and at subsequent routine practice visits. Patients were followed up until death, disease progression or change of treatment regimen, for a maximum of 8 months. Upon analysis, patients were classified into taxane single-agent (TM) or taxane-based combination (TC) cohorts according to scheduled first-line therapy. Logistic regression was used to investigate the relationship between choice of TM vs. TC and baseline factors.
Results:
Among the 465 patients enrolled (22.4% HER2+), 160 were prescribed TM (69% docetaxel, 31% paclitaxel) and 305 TC, frequently combined with gemcitabine (39%) or capecitabine (24%). HER2+ status was the only factor associated with choosing TC (p < 0.001). Median PFS 95% CI was 11.5 8.7-13.3 months for TM and 10.3 8.4-14.4 months for TC. Among HER2+ patients (N = 104), only 59% received trastuzumab, none had previous adjuvant trastuzumab. Median PFS was 19.7 9.3-unestimated months for TC including trastuzumab, 18.8 5.0-22.0 months for TC and 6.1 3.8-13.3 months for TM without trastuzumab.
Conclusions:
In patients from 12 different countries treated during routine practice, TCs were prescribed more frequently than single agents. HER2+ status was significantly associated with TC use. 41% of HER2+ patients received no anti-HER2 treatment; PFS results for TC with and without trastuzumab (19.7 and 18.8 months) suggested TCs without trastuzumab might be worth further investigation in these patients. However, the study was not randomized; treatment evaluation bias can therefore not be excluded.
Abstract Background SBAs are rarely seen tumors.Data regarding the use of chemotherapy together with bevacizumab in advanced SBA patients are lacking Materials and Methods The aim of this study is ...the evaluation of bevacizumab in advanced SBA. Twenty-eight patients from 5 centers with diagnosis of advanced SBA who received first-line treatments with modified FOLFOX6 (mFOLFOX6) and FOLFIRI chemotherapy regimens were involved in the study. All patients were divided into 2 groups; ones who received bevacizumab together with these chemotherapy regimens (Chemo+Bev group) and ones who did not receive bevacizumab (Chemo group) Results The median progression-free survival (PFS) and overall survival (OS) time of all population were 8.7 months and 16.9 months, respectively. Overall response rate (ORR) was 43.7% in Chemo group and 58.3% in Chemo+Bev group. Median PFSs in Chemo and Chemo+Bev groups were found to be 7.7 months and 9.6 months, respectively and median OS were 14.8 months and 18.5 months, respectively. There was not a significant difference between the groups in terms of ORR, PFS and OS Conclusion Although there was no significant difference in any of the outcomes, use of bevacizumab together with chemotherapy is a more effective treatment approach compared to chemotherapy alone and it does not cause an excess of significant toxicity.
BackgroundIn EMPOWER-Lung 1 (NCT03088540), a randomized 1:1 phase 3 open-label study comparing cemiplimab versus chemotherapy in patients with advanced NSCLC (aNSCLC) with PD-L1 ≥50%, clinically ...meaningful and statistically significant improvements in OS and PFS were observed. Better objective responses were observed with cemiplimab monotherapy versus platinum-doublet chemotherapy (odds ratio 2.53; 95% CI: 1.74–3.69; P<0.0001). To evaluate the effects of objective response on PROs, we performed exploratory analyses of patients with and without objective response, based on treatment arms combined and for each treatment arm separately.MethodsPROs were assessed at baseline and Day 1 of each treatment cycle for the first 6 cycles, then on Day 1 of every third cycle using the EORTC QLQ-C30 and QLQ-LC13 questionnaires. Higher scores indicated better global health status (GHS)/QoL. Patients were grouped by their RECIST-based objective response status (with versus without objective response) within each treatment arm. Mixed-effects model for repeated measures were performed to compare overall change from baseline GHS/QoL scores while controlling for baseline. Time to definitive clinically meaningful deterioration (TTD) (decrease of ≥10 points) for GHS/QoL was compared between patients with and without objective response using a stratified log-rank test and Cox proportional hazards model.ResultsFor the 2 treatment arms combined, an overall change from baseline in GHS/QoL significantly favored patients with versus those without objective response (9.71; 95% CI: 6.90–12.52). Overall change from baseline significantly favored patients with versus those without objective response in both the cemiplimab arm (9.36; 95% CI: 5.76–12.95) and chemotherapy arm (7.68; 95% CI: 3.65–11.71).For the 2 treatment arms combined, a significantly greater delay in TTD in GHS/QoL was observed in patients with objective response (median: not yet reached NYR) versus those without objective response (11.89 months; HR 0.29; 95% CI: 0.18–0.47). Likewise, a significantly greater delay in TTD in patients with versus those without objective response was also observed in both the cemiplimab arm (median: both NYR; HR 0.33; 95% CI: 0.18–0.58) and the chemotherapy arm (median: NYR for patients with objective response) versus those without objective response (11.89 months; HR 0.25; 95% CI: 0.11–0.60).ConclusionsIn patients with aNSCLC with PD-L1 ≥50%, overall change from baseline and TTD in GHS/QoL significantly favored patients with versus those without objective response. These results suggest that an objective response may lead to more favorable overall change from baseline and a greater delay in TTD in GHS/QoL among these patients.AcknowledgementsEditorial support was provided by Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc., and Sanofi. Responsibility for all opinions, conclusions, and data interpretation lies with the authors.Trial RegistrationNCT03088540Ethics ApprovalAll studies were approved by the institutional review board or ethics committee at each participating site. Informed written consent was obtained from all individual participants included in the studies.
Aim
To evaluate the CD8+CD28− and CD4+CD25+ regulatory T (Treg) cells in addition to other some lymphocyte subgroups in peripheral blood of advanced stage lung cancer patients.
Methods
The study ...group (
n
= 28) comprised chemotherapy and radiotherapy naïve patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). The control group (
n
= 22) consisted of age- and sex-matched healthy volunteers. Flow cytometry was used to count T cells, natural killer (NK) cells and CD4+CD25 Treg cells, and for CD8+ T cell subgroup analysis. Flow cytometry was performed and annexin V binding was used for apoptotic cell evaluation.
Results
In patient group, the percentage of CD8+CD28− cells among lymphocytes was elevated, and there was also an increase in the CD28−/CD28+ cell ratio among CD8 lymphocyte population. The distribution of CD8 cells was different in lung cancer patients when compared with the control group. The absolute count of CD4+CD25
bright
cells and the percentages of these cells among total lymphocytes were higher in the patient group. The Annexin V(+) cell percentages among CD8+CD28− and CD8+CD28+ lymphocytes were higher in the patient group than in the control group. No differences were found between the NSCLC and SCLC patients with respect to the hematological parameters and the distribution of lymphocyte subgroups. In NSCLC patients, the percentage of CD8+CD28− cells among the lymphocyte population was higher in patients with stage IV than those with stage III.
Conclusion
These findings may reflect the possibility of tumor-induced immunosuppression and they should be complemented with further studies.
Objectives: To analyze the relationship between clinical features, hormonal receptor status, and survival in patients who were diagnosed with medullary breast cancer (MBC). Methods: Demographic ...characteristics, histopathological features, and survival statuses of 201 patients diagnosed with MBC between 1995 and 2015 were retrospectively recorded. Survival analyses were conducted with uni- and multivariate cox regression analysis. Results: Median follow-up time was 54 (4-272) months. Median patient age at the time of diagnosis was 47 years old (26-90). Of the patients, 91.5% were triple negative. Five-year recurrence free survival time (RFS) rate was 87.4% and overalll survival (OS) rate 95.7%. For RFS, progesterone receptor (PR) negativity, atypical histopathological evaluation, absence of lymphovascular invasion, smaller tumor, lower nodal involvement were found to be favourable prognostic factors by univariate analysis (p<0.05). The PR negativity and smaller tumor were found to be favourable factors by univariate analysis (p<0.05). However, none of these factors were determined as significant independent prognostic factors for OS (p>0.05). Conclusion: Turkish MBC patients exhibited good prognosis, which was comparable with survival outcomes achieved in the literature. The PR negativity was related to a better RFS and OS rates.
Abstract Background Although studies have investigated whether a routine follow-up should be performed after a gastrectomy, no consensus has been reached on the significance of the follow-up or the ...optimal surveillance protocol. In the present study, we evaluated the significance of the presence or absence of symptoms in the detection of recurrences after curative gastrectomy for gastric cancer. Methods We retrospectively analyzed 173 patients with recurrent gastric cancer who underwent radical gastrectomy. We evaluated the prognostic significance of the presence of cancer-related symptoms at the diagnosis of recurrence, and the relationship between the presence of symptoms and other clinicopathological factors. Results We detected a symptomatic recurrence in 42.2% of patients. The presence of symptoms were significantly correlated with tumor size, pT stage, pN stage, pathologic stage, and short disease-free interval (<12 mo). The median disease-free survival (DFS), post-recurrence survival (PRS), and overall survival (OS) times for patients with asymptomatic recurrence were significantly longer than those of patients with symptomatic recurrence (disease-free survival was corrected as DFS, 11.1 versus 9.3 mo, P < 0.001; PRS, 4.9 versus 3.1 mo, P = 0.02; OS, 18.3 versus 12.3 mo, P = 0.001, respectively). Multivariate analysis showed that the presence of cancer-related symptoms ( P = 0.033; hazard ratio HR, 0.81) was an independent prognostic factor for PRS, as were short disease-free intervals ( P < 0.001; HR, 2.42), age ( P = 0.02; HR, 1.53), and the presence of chemotherapy in recurrence ( P = 0.001; HR, 0.49). In addition, multivariate analysis indicated that the presence of symptoms, short disease-free interval, and age were also independent prognostic indicators for OS. Conclusions Our results demonstrate that symptomatic recurrence is an important prognostic factor for PRS of patients with gastric cancer after a curative gastrectomy. The presence of symptomatic recurrence may be a new and beneficial prognostic marker to evaluate biologic aggressiveness, which is an important determinant of survival at the time of recurrence diagnosis during a follow-up for gastric cancer.
Aim
The goal of this study is to evaluate possible factors affecting the survival of patients treated with gonadotropin‐releasing hormone (GnRH) analogues.
Methods
Demographic characteristics, ...treatment modalities, overall survival (OS) and the possible factors affecting the survival a total of 554 premenopausal breast cancer patients in Turkey evaluated retrospectively.
Results
The median duration of GnRH analogues use was 22 ± 13.6 (range, 1–87) months. Patients were divided into three groups according to the duration of GNRH analogues use; 4–12 months (Group A), 13–24 months (Group B) and ≥25 months (Group C). Overall, 530 patients were analyzed; 23.2%, 45.8%, 30.9% of the patients were in Group A, B and C, respectively. The median follow‐up duration was 34 ± 30.3 (range, 4–188) months. The OS in patients ≤35 years of age was found to be significantly longer than that of patients >35 years of age in Group B (log rank, P = 0.023). The disease‐free survival of the patients in Group A was significantly shorter than that of patients in Group C (log rank, P = 0.003). The OS of Group A patients was significantly shorter in comparison to that of Group B and Group C patients (log rank, P = 0.000) and the OS of Group B patients was significantly shorter than Group C (log rank, P = 0,000).
Conclusion
There is currently no definite data on the optimal duration of GnRH analogues use. One of the important results of this study that will provide an insight to the future studies is the improvement gained in OS by the increase in the duration of GnRH analogues use.
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