Objective
The aim was to evaluate the role of immune check point inhibitors (ICIs) in patients with high‐grade upper tract urothelial carcinoma (UTUC) who are managed endoscopically when ...nephroureterectomy (NU) is not feasible, such as in patients who are either not candidates for NU or decline extirpative surgery.
Methods
All patients diagnosed with high‐grade UTUC and managed endoscopically between January 1996 and August 2022 were included in the study. Subsequently, patients were categorised based on their use of ICIs into group 1 (patients who did not receive ICIs) and group 2 (patients who received ICIs). Survival outcomes were assessed using Kaplan–Meier analysis, while a multivariable regression model was employed to analyse the impact of clinical characteristics on survival.
Results
A total of 29 patients were enrolled, with 14 in group 1 and 15 in group 2. Both groups exhibited similar demographic and disease characteristics, including multifocality, laterality and initial tumour size. The median follow‐up period was 29.2 months. Notably, group 2 demonstrated significantly enhanced overall and metastasis‐free survival rates compared to group 1. At 47.8 months, the overall survival rate was 0% (all patients died) in group 1, whereas it was 85.7% in group 2. Similarly, the metastasis‐free survival rate was 0% (all patients had metastatic disease) in group 1 at 40.6 months, whereas it reached 78.0% in group 2. The multivariable analysis indicated a correlation between ICI usage and improved survival outcomes, with a hazard ratio of 0.002.
Conclusion
Utilisation of adjuvant ICIs in the setting of endoscopically treated patients with high‐grade UTUC is associated with significantly improved survival rates. ICIs should be considered in this patient population, however, more studies with larger sample size are warranted.
Purpose
The purpose of this study is to evaluate the efficacy and safety of intravenous (IV) palonosetron in preventing chemotherapy-induced nausea and vomiting (CINV) in patients with cancer who had ...incomplete control of CINV during their previous cycle of low emetogenic chemotherapy (LEC).
Methods
Patients with histologically or cytologically confirmed cancer, ≥18 years of age, with a Karnofsky Performance Scale score of ≥50 % who had received LEC that induced vomiting and/or at least moderate nausea during their previous treatment cycle received palonosetron 0.25 mg IV 30 min before chemotherapy. Outcomes were recorded in patient diaries over 120 h and at an end-of-study visit on days 6, 7, or 8 after LEC administration. The primary efficacy variable was the complete response rate, defined as no emetic episodes and no rescue medication at 0–24 h (acute post-chemotherapy phase), 24–120 h (delayed phase), and 0–120 h (overall).
Results
Complete responses among the intent-to-treat study population (
n
= 34) were recorded for 88.2 % of patients in the acute phase, 67.6 % in the delayed phase, and 67.6 % overall. No emetic episodes occurred in 91.2 and 79.4 % of patients during the acute and delayed phases, respectively, and no nausea in 73.5 and 52.9 %, respectively. Palonosetron was well tolerated; only two patients experienced treatment-related adverse events.
Conclusions
Among the patients with cancer who had a history of CINV with LEC, palonosetron was effective in preventing CINV in both the acute and delayed post-chemotherapy phases, and was well tolerated. Randomized comparative studies in larger populations of patients receiving LEC are needed to confirm these findings.
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195
Background: Oxaliplatin is commonly used to treat many GI cancers, especially colorectal (CRC), pancreatic (PC), and gastric (GC); however, peripheral neuropathy (PN) is the ...dose-limiting toxicity. Duloxetine (DL) is a second-generation selective serotonin and norepinephrine reuptake inhibitor (SNRI) used for the treatment of depression, anxiety, PN-associated with diabetes or ongoing pain due to medical conditions such as fibromyalgia. In this retrospective study, we evaluated the role of DL in reduction of oxaliplatin-induced neuropathy. Methods: Patients with GI cancers receiving oxaliplatin-based chemotherapy regimens from Nov 2016 to Nov 2019 were included. Patients with pre-existing PN from other etiologies such as diabetes, alcoholism, autoimmune disease, infections, hereditary, etc. were excluded. Neurological evaluations were performed serially before initiating DL and every 4 weeks thereafter according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. DL was given at 30 mg by mouth (PO) once daily and if tolerated after 3 days, was escalated to 60 mg once daily. Response was calculated to include number of patients with stable PN, improved PN, or no benefit. Adverse toxicities were graded. Results: 53 patients with median age of 53 years (range: 38 – 72) received DL for oxaliplatin-induced PN during treatment of GI cancers (CRC: 40%, PC:30%, GC: 10%, others: 10%). Improvement in PN from higher to lower grades was witnessed at 2 weeks in only 4 patients. At 4 week of DL, 3/53 (6%) patients improved from G3 PN to G2, 6/53 (11%) from G3 to G1, and 28/53 (52.8%) from G2 to G1, 14/53 (26%) and 2/53 (4%) had stable G3 and G2 PN respectively. At 8 week of DL, 10/53 (19%) of patients improved from G3 to G2, 3/53 (6%) from G2 to G1, 23/53 (43%) from G1 to G0, while 11/53 (21%), 2/53 (4%) and 4/53 (8%) remained stable at G1, G2 and G3 respectively. Overall DL resulted in a response rate of 89% and stable PN in 11%. 5 patients had to stop DL due to G3 drowsiness, insomnia, dry mouth and headache. Overall, DL was well-tolerated with majority of toxicities in G1-2 grade: dizziness (15%), drowsiness (11%), sexual side effects (11%), dry mouth (11%), insomnia (8%), headache (8%). In addition to PN, DL helped in improving depression in 50% of these patients and decreased the pain score in an additional 23%. Conclusions: DL resulted in a clinically significant improvement in PN-induced by oxaliplatin with manageable toxicity profile. Additionally, DL also improved depression and pain score. DL may be considered as an option in ameliorating PN in these patients, however, caution must be taken about DL and other drugs interaction. Our study warrants a prospective randomized trial to study the effectiveness of DL in treating oxaliplatin-induced PN. Moreover, cost effectiveness of DL in concurrently improving PN, depression and pain needs to be studied as well.
Abstract
Objective:
Everolimus (EVE)+exemestane (EXE; n = 485) more than doubled median progression-free survival versus placebo (PBO) + EXE (n = 239), with a manageable safety profile and no ...deterioration in health-related quality-of-life (HRQOL) in patients with hormone-receptor-positive (HR+) advanced breast cancer (ABC) who recurred or progressed on/after nonsteroidal aromatase inhibitor (NSAI) therapy. To further evaluate EVE + EXE impact on disease burden, we conducted additional post-hoc analyses of patient-reported HRQOL.
Research design and methods:
HRQOL was assessed using EORTC QLQ-C30 and QLQ-BR23 questionnaires at baseline and every 6 weeks thereafter until treatment discontinuation because of disease progression, toxicity, or consent withdrawal. Endpoints included the QLQ-C30 Global Health Status (QL2) scale, the QLQ-BR23 breast symptom (BRBS), and arm symptom (BRAS) scales. Between-group differences in change from baseline were assessed using linear mixed models with selected covariates. Sensitivity analysis using pattern-mixture models determined the effect of study discontinuation on/before week 24. Treatment arms were compared using differences of least squares mean (LSM) changes from baseline and 95% confidence intervals (CIs) at each timepoint and overall.
Clinical trial registration:
Clinicaltrials.gov: NCT00863655.
Main outcome measures:
Progression-free survival, survival, response rate, safety, and HRQOL.
Results:
Linear mixed models (primary model) demonstrated no statistically significant overall difference between EVE + EXE and PBO + EXE for QL2 (LSM difference = −1.91; 95% CI = −4.61, 0.78), BRBS (LSM difference = −0.18; 95% CI = −1.98, 1.62), or BRAS (LSM difference = −0.42; 95% CI = −2.94, 2.10). Based on pattern-mixture models, patients who dropped out early had worse QL2 decline on both treatments. In the expanded pattern-mixture model, EVE + EXE-treated patients who did not drop out early had stable BRBS and BRAS relative to PBO + EXE.
Key limitations:
HRQOL data were not collected after disease progression.
Conclusions:
These analyses confirm that EVE + EXE provides clinical benefit without adversely impacting HRQOL in patients with HR+ ABC who recurred/progressed on prior NSAIs versus endocrine therapy alone.
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125
Background: BOLERO-2, a phase III study, randomized 724 patients with hormone-receptor–positive metastatic breast cancer, who had recurrence or progression on/after prior ...nonsteroidal aromatase inhibitor therapy, to everolimus (EVE) + exemestane (EXE) or EXE + placebo. A preplanned 12-mo median time interim analysis demonstrated that EVE + EXE significantly improved progression-free survival (PFS) vs EXE + placebo, but EVE + EXE resulted in a higher rate of grade 3-4 toxicity. Per-protocol patients reported HRQoL data are limited; here we report on additional post hoc analyses of these outcomes. Methods: Using the EORTC QLQ-C30 questionnaire, HRQoL was assessed at baseline and every 6 weeks thereafter until progression. QLQ-C30 consists of 30 items combined into 15 subscales, including a Global Health Status (GHS), where higher scores (range, 0-100) indicate better HRQoL. Analysis included a protocol-specified time to definitive deterioration (TTD) analysis at a 5% decrease in QoL relative to baseline, with no subsequent increase above this threshold. We report additional sensitivity analyses using 10-point minimally important difference (MID) decreases in QLQ-C30 score relative to baseline. Treatment arms were compared using a stratified log-rank test and a Cox proportional hazards model adjusted for trial stratum (visceral metastases and previous hormone sensitivity), age, sex, race, baseline score, ECOG performance status, prognostic risk factors, and treatment history. Results: Baseline QLQ-C30 GHS scores were not statistically significantly different across treatment groups (64.7 vs 65.3; difference –0.7 95% CI, –4.3-3.0). Median TTD in HRQoL was 7.0 mo (95% CI, 5.6-8.3) for EVE + EXE vs 5.6 (95% CI, 4.2-7.0) for EXE (p = .0792). Adjusted HR (0.80) approached significance (95% CI, 0.63-1.02). At the 10-point MID, median TTD for EVE + EXE was 9.7 mo (95% CI, 8.3-11.2) vs 8.4 mo (95% CI, 6.3-12.5) for EXE. Adjusted HR was 0.90 (95% CI, 0.69-1.18). Conclusions: These additional analyses from the BOLERO-2 study demonstrate that in addition to significantly improving PFS, EVE + EXE does not compromise HRQoL.
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155
Background: The phase III BOLERO-2 study at 18 months’ median follow-up showed that everolimus (EVE) + exemestane (EXE) significantly improved progression-free survival (PFS) vs EXE ...alone in 724 patients with hormone receptor–positive (HR+) advanced breast cancer (ABC) with recurrence/progression during/after nonsteroidal aromatase inhibitor (NSAI) therapy. A higher rate of grade 3/4 adverse events was noted with EVE + EXE but was not associated with deterioration in quality of life (QOL) based on the EORTC QLQ-C30 Global Health Status scale. Additional patient-reported post hoc analyses of QOL are reported herein. Methods: During BOLERO-2, QOL (EORTC QLQ-C30 and QLQ-BR23) was assessed at baseline and q 6 wk thereafter until progression or discontinuation. Physical, emotional, and social functioning subscales of QLQ-C30 were analyzed. Time to definitive deterioration (TTD) was defined based on either a 5% (protocol-specified) or a 10-point (more stringent) decrease from baseline for each subscale and analyzed by Kaplan-Meier methods. The difference between treatments was assessed by a log-rank test stratified by randomization factors. Results: QLQ-C30 compliance was >80% at week 48. Among the 3 protocol-specified QLQ-C30 subscales, analyses based on a 5% decrease in QOL showed a longer TTD for both physical and emotional functioning in the EVE + EXE group vs EXE alone (log-rank p = 0.0120 and p = 0.0277, respectively). The TTDs for social functioning were similar in both treatment arms (log-rank p = 0.3374). Analyses based on a 10-point decrease indicated a longer TTD for physical functioning in the EVE + EXE group (15.2 mo) vs EXE alone (9.7 mo; log-rank p = 0.0211). The TTDs for emotional and social functioning were similar between EVE + EXE and EXE alone: 13.9 vs 13.8, respectively (log-rank p = 0.4023), and 11.5 vs 9.5, respectively (log-rank p = 0.2507). Conclusions: The treatment goal for ABC is to maximize clinical benefit with minimal negative effects on QOL. These additional BOLERO-2 QOL analyses confirmed that the more than doubling of PFS with EVE + EXE was accompanied by maintained physical, emotional, and social functioning compared with EXE alone in patients with HR+ ABC progressing after NSAI. Clinical trial information: NCT00863655.
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553
Background: The phase 3 BOLERO-2 study at 18 months’ median follow-up showed that everolimus (EVE) + exemestane (EXE) significantly improved progression-free survival (PFS) vs EXE ...alone in 724 hormone-receptor–positive (HR
+
) advanced breast cancer (ABC) patients with recurrence/progression during/after nonsteroidal aromatase inhibitor (NSAI) therapy. A higher rate of grade 3/4 adverse events was noted with EVE + EXE, but was not associated with deterioration in quality of life (QOL) based on the EORTC QLQ-C30 Global Health Status scale. Additional patient-reported post hoc analyses of QOL are reported herein. Methods: During BOLERO-2, QOL (EORTC QLQ-C30 and QLQ-BR23) was assessed at baseline and q 6 wk thereafter until progression or discontinuation. Physical, emotional, and social functioning subscales of QLQ-C30 were analyzed. Time to definitive deterioration (TTD) was defined based on either a 5% (protocol specified) or 10-point (more stringent) decrease from baseline for each subscale and analyzed by Kaplan-Meier methods. The difference between treatments was assessed by a log-rank test stratified by randomization factors. Results: QLQ-C30 compliance was > 80% at week 48. Among the 3 protocol-specified QLQ-C30 subscales, analyses based on a 5% decrease in QOL showed a longer TTD for both physical and emotional functioning in the EVE + EXE group vs EXE alone (log-rank P = .0120 and P = .0277, respectively). The TTD for social functioning was similar in both treatment arms (log-rank P = .3374). Analyses based on a 10-point decrease indicated a longer TTD for physical functioning in the EVE + EXE group (15.2 mo) vs EXE alone (9.7 mo; log-rank P = .0211). The TTDs for emotional and social functioning were similar between EVE + EXE and EXE alone: 13.9 vs 13.8, respectively (log-rank P = .4023), and 11.5 vs 9.5, respectively (log-rank P = .2507). Conclusions: The treatment goal for ABC is to maximize clinical benefit with minimal negative effects on QOL. These additional BOLERO-2 QOL analyses confirmed that the more than doubling of PFS with EVE + EXE was accompanied by maintained physical, emotional, and social functioning compared with EXE alone in patients with HR
+
ABC progressing after NSAI. Clinical trial information: NCT00863655.
