Cisplatin versus carboplatin-based chemotherapy in inoperable or recurrent urothelial carcinoma: A retrospective analysis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14558-14558
Author(s):  
A. Bamias ◽  
E. Kastritis ◽  
G. Bozas ◽  
V. Koutsoukou ◽  
N. Antoniou ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Combination Chemotherapy ◽  
Cox Regression ◽  
Distant Metastases ◽  
First Line ◽  
Cox Regression Analysis ◽  
The Poor ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Poor Tolerance

14558 Background: Cisplatin-based chemotherapy represents the standard for patients with inoperable or recurrent urothelial carcinoma. Carboplatin-based chemotherapy is reserved for not-fit-for-cisplatin patients. Recent data suggest that carboplatin-based chemotherapy may be effective in fit-for-cisplatin patients. We examined the differences in the outcome according to the compound used as first-line treatment. Methods: We selected patients who received first-line combination chemotherapy based on cisplatin or carboplatin. The major end point was survival. Survival curves were estimated with the Kaplan-Meier method, while cox regression analysis was used for multivariate models. Results: 445 patients, treated with cisplatin (330) or carboplatin (115)-based chemotherapy were included in this analysis. After a median follow-up of 52 months, there was no significant difference in survival between the two treatment groups (Table). Subgroup analyses according to PS, distant metastases, Hb, weight loss, showed that the use of cisplatin was independently associated with improved survival only in the PS 2,3 subgroup (see Table). When patients were stratified according to the Bajorin prognostic criteria (PS 0,1 vs. 2,3 and/or distant metastases yes vs. no; J Clin Oncol 1999, 17: 3173), again cisplatin-based chemotherapy was associated with a trend towards improved outcome only in the worst prognostic group (Table). Conclusions: Carboplatin-based chemotherapy may be equally effective to cisplatin-based treatment in patients with inoperable or recurrent urothelial cancer and no or one adverse factors. Cisplatin-based treatment may be beneficial in patients with poor prognosis. Nevertheless, the clinical relevance of this superiority is limited due to the poor outcome and the poor tolerance of cisplatin-based combination chemotherapy in this group of patients. (see Table) Median survival (95% CI) after first-line chemotherapy for advanced urothelial carcinoma. [Table: see text] No significant financial relationships to disclose.

Short-term outcomes associated with temozolomide or PCV chemotherapy for 1p/19q-codeleted WHO grade 3 oligodendrogliomas: a national evaluation

2022 ◽  
Author(s):  
Nayan Lamba ◽  
Malia McAvoy ◽  
Vasileios K Kavouridis ◽  
Timothy R Smith ◽  
Mehdi Touat ◽  
...  
Keyword(s):  
Cox Regression ◽  
Extent Of Resection ◽  
First Line ◽  
Short Term ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
Pcv Chemotherapy ◽  
Grade 3 ◽  
National Analysis

Abstract Background The optimal chemotherapy regimen between temozolomide and procarbazine, lomustine, and vincristine (PCV) remains uncertain for W.H.O. grade 3 oligodendroglioma (Olig3) patients. We therefore investigated this question using national data. Methods Patients diagnosed with radiotherapy-treated 1p/19q-codeleted Olig3 between 2010-2018 were identified from the National Cancer Database. The OS associated with first-line single-agent temozolomide vs. multi-agent PCV was estimated by Kaplan-Meier techniques and evaluated by multivariable Cox regression. Results 1,596 radiotherapy-treated 1p/19q-codeleted Olig3 patients were identified: 88.6% (n=1,414) treated with temozolomide and 11.4% (n=182) with PCV (from 5.4% in 2010 to 12.0% in 2018) in the first-line setting. The median follow-up was 35.5 months (interquartile range [IQR] 20.7-60.6 months) with 63.3% of patients alive at time of analysis. There was a significant difference in unadjusted OS between temozolomide (5yr-OS 58.9%, 95%CI: 55.6-62.0) and PCV (5yr-OS 65.1%, 95%CI: 54.8-73.5; p=0.04). However, a significant OS difference between temozolomide and PCV was not observed in the Cox regression analysis adjusted by age and extent of resection (PCV vs. temozolomide HR 0.81, 95%CI: 0.59-1.11, p=0.18). PCV was more frequently used for younger Olig3s, but otherwise was not associated with patient’s insurance status or care setting. Conclusions In a national analysis of Olig3s, first-line PCV chemotherapy was associated with a slightly improved unadjusted short-term OS compared to temozolomide; but not following adjustment by patient age and extent of resection. There has been an increase in PCV utilization since 2010. These findings provide preliminary data while we await the definitive results from the CODEL trial.

Assessment of Losartan 50 mg on Survival of Post-Dialysis Euvolemic Hypertensive Patients: Findings from HELD Trial

2019 ◽  
Vol 48 (3) ◽  
pp. 233-242
Author(s):  
Raja Ahsan Aftab ◽  
Amer Hayat Khan ◽  
Azreen Syazril Adnan ◽  
Syed Azhar Syed Sulaiman ◽  
Tahir Mehmood Khan
Keyword(s):  
Cox Regression ◽  
Dialysis Session ◽  
Hypertensive Patients ◽  
Cox Regression Analysis ◽  
Probability Of Survival ◽  
End Point ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Single Blind

Aims and objective: To estimate the effect of losartan 50 mg on survival of post-dialysis euvolemic hypertensive patients. Methodology: A single center, prospective, single-blind randomized trial was conducted to estimate the survival of post-dialysis euvolemic hypertensive patients when treated with lorsartan 50 mg every other day. Post-dialysis euvolemic assessment was done by a body composition monitor. Covariate Adaptive Randomization was used for allocation of participants to the standard or intervention arm, and the follow-up duration was twelve months. The primary end point was achieving targeted blood pressure (BP) of <140/90 mm Hg and maintaining for 4 weeks, whereas secondary end point was all cause of mortality. Pre-, intra-, and post-dialysis session BP measurements were recorded, and survival trends were analyzed using Kaplan-Meier analysis. Results: Of the total 229 patients, 96 (41.9%) were identified as post-dialysis euvolemic hypertensive. Final samples of 88 (40.1%) patients were randomized into standard (n = 44) and intervention arms (n = 44), and 36 (81.8%) patients in each arm completed a follow-up of 12 months. A total of eight patients passed away during the 12-month follow-up period (6 deaths among standard arm and 2 in intervention arm). However, the probability of survival between both arms was not significant (p = 0.13). Cox regression analysis revealed that chances of survival were higher among the patients in the intervention (OR 3.17) arm than the standard arm (OR 0.31); however, the survival was found not statistically significant. Conclusion: There was no statistical significant difference in 1 year survival of post-dialysis euvolemic hypertensive patients when treated with losartan 50 mg.

scholarly journals RET Cys634Arg mutation confers a more aggressive multiple endocrine neoplasia type 2A phenotype than Cys634Tyr mutation

2015 ◽  
Vol 172 (3) ◽  
pp. 301-307 ◽  
Author(s):  
Nuria Valdés ◽  
Elena Navarro ◽  
Jordi Mesa ◽  
Anna Casterás ◽  
Victoria Alcázar ◽  
...  
Keyword(s):  
Amino Acid ◽  
Multiple Endocrine Neoplasia ◽  
Cox Regression ◽  
Multiple Endocrine Neoplasia Type ◽  
Distant Metastases ◽  
National Database ◽  
Cox Regression Analysis ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Kaplan Meier

ObjectiveSpecific germline mutations in the RET proto-oncogene are correlated with clinical features in multiple endocrine neoplasia type 2A (MEN2A); however, data are scarce regarding differences in clinical profiles dependent on the type of nucleotide and amino acid substitution at the same codon. We aimed to analyse differences in clinical risk profiles and outcomes among different amino acids encoded by codon 634.DesignThe study was retrospective and multicentric.MethodsWe collected data included in the Spanish Online National Database from patients with MEN2A carrying a RET proto-oncogene mutation on codon 634. The mean follow-up time was 7.6±6.9 years (1–32).ResultsPatients (n=173) from 49 unrelated families were C634Y carriers, and 26 patients from eight different families had C634R mutation. We found higher penetrance of medullary thyroid carcinoma, phaeochromocytoma and hyperparathyroidism (P<0.001, P=0.007 and P<0.001 respectively) in C634R carriers than in C634Y carriers. The Kaplan–Meier estimate of cumulative lymph node and distant metastases rates showed that these events occurred earlier in patients harbouring the C634R mutation (P<0.001). A multivariate adjusted Cox regression analysis indicated that the C634R mutation was an independent factor for persistent/recurrent disease (hazard ratio, 3.17; 95% CI: 1.66–6.03; P<0.001).ConclusionsOur results suggest that there could be clinical differences caused by different amino acid substitutions at codon 634; specifically, the C634R mutation was associated with a more aggressive MEN2A phenotype than the C634Y mutation.

Prognostic Analysis of Diagnostic Ureteroscopic Biopsy for Intravesical Recurrence of Upper Urinary Tract Urothelial Carcinoma

2021 ◽  
pp. 1-9
Author(s):  
Han Chen ◽  
Ming Wang ◽  
Tonghui Weng ◽  
Yu Wei ◽  
Lei Yang ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Urothelial Carcinoma ◽  
Cox Regression ◽  
Bladder Tumour ◽  
Upper Urinary Tract ◽  
Cox Regression Analysis ◽  
Prognostic Analysis ◽  
Kaplan Meier ◽  
High Risk Factor ◽  
Urinary Tract Urothelial Carcinoma

<b><i>Objective:</i></b> The aim of this study was to investigate whether diagnostic ureteroscopy (URS) biopsy is unfavourable for bladder tumour recurrence in upper urinary tract urothelial carcinoma (UTUC). <b><i>Materials and Methods:</i></b> We performed a retrospective analysis of 195 patients diagnosed with UTUC, who were divided into a diagnostic URS group (URS+) and a nondiagnostic URS group (URS–) according to whether diagnostic ureteroscopic biopsy was performed. A Cox regression model was used to analyse the risk factors for intravesical recurrence (IVR)-free survival (IRFS) and overall survival (OS) in UTUC after radical nephroureterectomy (RNU). Kaplan-Meier analysis was used to estimate the influence of factors on the incidence of IVR and the cumulative survival rate of UTUC. <b><i>Results:</i></b> Patients with a maximum tumour diameter of less than 3.1 cm, low-stage tumours, and ureteral tumours were more likely to undergo diagnostic URS before radical surgery. Multivariate Cox regression analysis showed that tumour pathological stage and diagnostic ureteroscopic biopsy can be used as predictors of IVR after RNU (<i>p</i> = 0.019, 0.033). Kaplan-Meier survival analysis found that diagnostic ureteroscopic biopsy was a high-risk factor for IRFS (<i>p</i> = 0.034). Subcomponent analysis showed that pTa/Tis/T1, pT2, pT3/pT4 stage, and diagnostic ureteroscopic biopsy with pTa/Tis/T1 stage were unfavourable for IVR (<i>p</i> = 0.047). <b><i>Conclusion:</i></b> Diagnostic ureteroscopic biopsy before RNU should be carefully selected for patients with atypical preoperative UTUC. We believe that intravesical chemotherapy drug perfusion can be used after surgery to prevent IVR if biopsy is unavoidable, but this still requires further prospective studies.

scholarly journals The role of radiotherapy in neuroendocrine cervical cancer: SEER-based study

2021 ◽  
Vol 104 (2) ◽  
pp. 003685042110093
Author(s):  
Meilian Dong ◽  
Xiaobin Gu ◽  
Taoran Ma ◽  
Yin Mi ◽  
Yonggang Shi ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cox Regression ◽  
Local Treatment ◽  
Seer Database ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Chi Squared ◽  
Seer Data

Background: There are few randomised prospective data or guidelines for the treatment of neuroendocrine cervical cancer (NECC). In addition, the role of radiotherapy (RT) in NECC remains controversial. We used the Surveillance Epidemiology and End Results (SEER) database to investigate the role of RT for the treatment of NECC. Particular attention was paid to the different role of RT in patients with or without a metastasis (M1 or M0). Methods: The SEER database was queried for studies on NECC. We limited the year of diagnosis to the years 2000 to 2015. A Pearson’s two-sided Chi-squared test, the Kaplan–Meier method and Cox regression analysis models were used for statistical analyses. The overall survival (OS) was studied for the overall group and between-subgroup groups. Results: NECC was an aggressive disease with a mean OS of only 46.3 months (range of 0–196 months, median of 23 months). No significant differences were shown between the surgery (S) and S + RT groups ( p = 0.146) in the M0 (without metastasis) arm. However, there was a statistically significant difference in OS between the S and S + RT groups in the M1 (with metastasis) arm (median of 44.6 months for the S group and 80.9 months for the S + RT group), p = 0.004. The mean survival was significantly longer for M0 patients than for M1 patients when treated with S only (S arm), that is, 82.1 months versus 44.6 months, respectively (log-rank p = 0.000). We also noted that when patients received adjuvant RT (S + RT arm), there were no significant differences between the M0 and M1 groups (median of 90.6 and 81.0 months, p = 0.704, respectively). Age at diagnosis, chemotherapy, T stage and N stage were significant factors for OS in the M0 arm. Interestingly, radiotherapy was the only significant factor for OS with a multivariate HR for death of 0.502 (95% CI 0.206–0.750, p = 0.006) in the M1 arm. Conclusions: RT may be carefully used in patients who are negative for metastases. Using SEER data, we identified a significant survival advantage with the combination of radiotherapy and surgery in NECC with metastases. This suggests that active local treatment should be conducted and has a significant impact on OS, even if a distant metastasis has occurred.

scholarly journals Salvage therapies for radiation-relapsed IDH-mutant astrocytoma and 1p/19q codeleted oligodendroglioma

2021 ◽  
Author(s):  
Sirui Ma ◽  
Soumon Rudra ◽  
Jian L Campian ◽  
Milan G Chheda ◽  
Tanner M Johanns ◽  
...  
Keyword(s):  
Cox Regression ◽  
Salvage Surgery ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Cancer Center ◽  
First Line ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Tertiary Cancer Center

Abstract Background Optimal management for recurrent IDH-mutant glioma after radiation therapy (RT) is not well-defined. This study assesses practice patterns for managing recurrent IDH-mutant astrocytoma (Astro) and 1p/19q codeleted oligodendroglioma (Oligo) after RT and surveys their clinical outcomes after different salvage approaches. Methods Ninety-four recurrent Astro or Oligo patients after RT who received salvage systemic therapy (SST) between 2001 and 2019 at a tertiary cancer center were retrospectively analyzed. SST was defined as either alkylating chemotherapy (AC) or non-alkylating therapy (non-AC). Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method from the start of SST. Multivariable analysis (MVA) was conducted using Cox regression analysis. Results Recurrent Oligo (n=35) had significantly higher PFS (median: 3.1 vs 0.8 years, respectively, P = 0.002) and OS (median: 6.3 vs 1.5 years, respectively, P &lt; 0.001) than Astro (n=59). Overall, 90% of recurrences were local. Eight-three percent received AC as the first-line SST; 50% received salvage surgery before SST; approximately 50% with local failure &gt;2 years after prior RT received reirradiation. On MVA, non-AC was associated with worse OS for both Oligo and Astro; salvage surgery was associated with improved PFS and OS for Astro; early reirradiation was associated with improved PFS for Astro. Conclusions Recurrent radiation-relapsed IDH-mutant gliomas represent a heterogeneous group with variable treatment approaches. Surgery, AC, and reirradiation remain the mainstay of salvage options for retreatment.

Presence of CTCs and its prognostic potential compared to AR-V7 expression in mCRPC undergoing androgen-deprivation therapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17032-e17032
Author(s):  
Katrin Schlack ◽  
Konstantin Seitzer ◽  
Verena Humberg ◽  
Neele Wüstmann ◽  
Norbert Grundmann ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Regression Analysis ◽  
Regression Models ◽  
Cox Regression ◽  
Androgen Deprivation ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Psa Response ◽  
Visceral Metastases

e17032 Background: Biomarkers predicting response to mCRPC treatment are rare. CTCs and AR-V7 status have been discussed as potential prognosticators. Methods: We evaluated 64 patients (pts.) treated with abiraterone (n=47) or enzalutamide (n=17), determined CTCs and analyzed AR-V7 status in correlation with survival using Kaplan-Meier-estimates and Cox-regression-models. Results: For PSA response, CTC- vs. CTC+ were not different (p=0.25) whereas AR-V7 status was predictive (68.2% AR-V7- and 33.3% AR-V7+ pts. (p=0.01)). Median PSA PFS was 17 mo. (CI 9.5-24.5) for CTC- and 6 (CI 5.2-6.9) for CTC+ pts. (p<0.01) with 9 mo. (CI 4.2-13.8) for CTC+/AR-V7- and 5 (CI 3.0–7.0) for CTC+/AR-V7+ pts. (p=0.04). In univariate cox regression analysis (UV), prior abiraterone or enzalutamide (A/E) (p=0.01), bone metastases (p=0.03), CTC+ (p=0.01), AR-V7+ (p=0.01), Hb ≤12 g/dl (p=0.01) and PSA decline ≥50% (p<0.01) were significant prognosticators. Within the CTC+ subgroup, AR-V7+ (p=0.02) and PSA decline ≥50% (p=0.03) showed a relevant difference. In multivariate analysis (MV), for CTC+ pts, AR-V7+ (p=0.02), PSA decline ≥50% (p=0.02) and visceral metastases (p=0.02) remained independent prognosticators. The analysis for PFS resulted in 22 mo. (CI NA) for CTC- compared to 9 (CI 7.7-10.3) for CTC+ (p=0.01) and 10 mo. (CI 8.2-11.8) for CTC+/AR-V7- vs. 6 (CI 1.9-10.1) for CTC+/AR-V7+ (p=0.07). Performing UV, prior A/E (p<0.01), CTC+ (p=0.01), AR-V7+ (p=0.01), Hb ≤12 (p<0.01), PSA decline ≥50% (p<0.01) and ALP elevated at baseline (p=0.03) showed statistically significant differences. Within the CTC+ subgroup, prior A/E (p=0.01), visceral metastases (p=0.02), Hb ≤12 (p=0.01) and PSA decline ≥50% (p=0.03) were significant prognosticators, whereas AR-V7+ was not. In MV of CTC+ pts, visceral metastases (p=0.02), PSA decline ≥50% (p=0.02) and Hb ≤12 (p=0.05) remained independent prognosticators. Median OS was not reached for CTC- and 17 mo. (CI 9.8–24.2) for CTC+ (p<0.01) with 27 (CI 10.6-43.4) vs. 14 (CI 10.4-17.7) mo. for AR-V7- and AR-V7+, respectively (p=0.06). UV resulted in statistically relevant differences for prior docetaxel (p=0.01), prior A/E (p<0.01), visceral metastases (p=0.02), CTC+ (p=0.01), AR-V7+ (p<0.01) and Hb ≤12 (p< 0.01). Within CTC+, prior docetaxel (p<0.01), prior A/E (p=0.01), visceral metastases (p<0.01) and Hb ≤12 (p<0.01) were statistically relevant parameters. UV for AR-V7 status did not result in a significant difference for OS either. In MV, CTC status as well as Hb ≤12 remained independent prognosticators (p=0.04 and p<0.01, respectively). For MV of CTC+, visceral metastases (p=0.01), Hb ≤12 (p<0.01) and prior docetaxel (p=0.01) were independent prognosticators of OS. Conclusions: Presence of CTCs seems to prognosticate PFS and OS in mCRPC patients undergoing Androgen-deprivation while presence of AR-V7 does not despite its predictive potential.

A multicenter, retrospective study on impact of immunotherapy in urothelial carcinoma with bone metastases (Meet-Uro01 Study).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 401-401
Author(s):  
Patrizia Giannatempo ◽  
Laura Marandino ◽  
Daniele Raggi ◽  
Francesco Pierantoni ◽  
Marco Maruzzo ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Urothelial Carcinoma ◽  
Cox Regression ◽  
Advanced Disease ◽  
Performance Status ◽  
Single Agent ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Dismal Prognosis ◽  
Ecog Ps

401 Background: Considerable numbers of patients (pts) with metastatic urothelial carcinoma (mUC) (approximately 25-47%) develop bone metastases (BoM). Their impact on the efficacy of immunotherapy (IO) is not yet sufficiently investigated. We developed a national collaboration on this issue, with the aim to assess the effect of BoM on survival outcomes of immunotherapy-treated pts in a large retrospective cohort. Methods: Data on pts diagnosed with mUC and treated between 07/14 and 08/20 with single-agent immunotherapy (IO) after failure of at least 1 previous line of chemotherapy (CT) for advanced disease, or (neo-)adjuvant CT within 12 months were retrospectively collected across 14 centers. PFS and OS were analyzed using the Kaplan-Meier method. Cox regression analysis was performed evaluating potential prognostic factors for OS and PFS. Each factor was evaluated in univariable (UV) and multivariable (MVA) analysis. Results: A total of 208 evaluable pts treated with single-agent immunotherapy (anti PD-1 n=42; anti PD-L1 n=166) were identified, including 122 without BoM (59% BoM-) and 86 (41%) BoM+. 13% of pts had progressed within 12 months after (neo-)adjuvant CT and 79% after a previous line of platinum-based CT for advanced disease (cisplatin 42.8%; carboplatin 36.5%). The presence of BoM negatively affected performance status (PS) of patients at baseline (ECOG PS 0/1/2 in 58% / 37% / 5% in BoM- vs 38% / 52% / 9% in BoM+; p=0.017). Other baseline characteristics were comparable. BoM+ showed shorter PFS (median 2.0 vs 2.6 months, HR 1.76 [95%CI, 1.31-2.37], p<0.001) and OS (median 3.9 vs 7.8 months, HR 1.59 [95%CI, 1.15-2.20], p=0.005) than BoM-. Probability of being alive was 62% vs 40% after 6 months, 38% vs 23% after 1 year and 24% vs 13% after 2 years, in BoM- and BoM+ respectively. Within each Bellmunt score, PFS and OS of BoM+ pts were shorter compared to BoM-. Both BoM and higher Bellmunt risk score were significantly associated with shorter PFS and OS in UV and MV analyses (Table). Conclusions: Patients with mUC treated with single-agent immunotherapy for BoM+ advanced disease have a dismal prognosis compared with BoM-. Further research is needed to understand the mechanism behind these clinical outcomes. [Table: see text]

Cisplatin-based combination chemotherapy in elderly patients with metastatic urothelial cancer.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 269-269
Author(s):  
Aristotelis Bamias ◽  
Susanne Krege ◽  
Chia-Chi Lin ◽  
Noah M. Hahn ◽  
Thorsten Ecke ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Urothelial Carcinoma ◽  
Combination Chemotherapy ◽  
Age Groups ◽  
First Line ◽  
Significant Difference ◽  
Visceral Metastases ◽  
Metastatic Urothelial Carcinoma ◽  
Baseline Characteristics ◽  
Two Age Groups

269 Background: Cisplatin-based combination chemotherapy is considered standard first-line treatment for patients with metastatic urothelial carcinoma. However, cisplatin-based chemotherapy is frequently avoided in elderly patients due to concerns regarding treatment-related toxicities. We analyzed the efficacy, and tolerability, of cisplatin-based chemotherapy in two age groups (< 70 versus ≥ 70 years old). Methods: Individual patient data was pooled from eight phase II and III trials evaluating cisplatin-based first-line chemotherapy in patients with metastatic urothelial carcinoma. Toxicities, treatment delivery, response proportions, and survival outcomes were compared between patients < 70 versus ≥ 70 years old. Results: Of the 543 patients included in the analysis, 162 patients (30%) were ≥ 70 years old. Patients ≥ 70 years old had a significantly lower baseline calculated creatinine clearance (57 vs. 73 ml/min, p<0.0001). All other baseline characteristics, including PS and visceral metastases were well balanced between the two age groups. Patients ≥ 70 years received a median of 1 cycle less of chemotherapy compared with younger patients (median cycles 5 versus 6; p = 0.004). There was no significant difference in the proportions of patients experiencing Grade 3-4 renal failure, febrile neutropenia, or treatment-related death. Response rate among patients ≥ 70 years old was 50% compared to 52% for patients < 70 years old (p=0.65). There was no significant difference in survival between the age groups (p=0.91). The median survival of the patients ≥ 70 years old was 12.1 months compared to 12.8 months for patients < 70 years old. There was no significant difference in survival between age groups when controlling for baseline performance status and/or the presence of visceral metastases. Conclusions: Elderly patients, with adequate renal function and other baseline characteristics suitable for clinical trial enrollment, tolerate cisplatin-based chemotherapy similarly, and achieve comparable clinical outcomes, compared with their younger counterparts. Cisplatin-based therapy need not be withheld from such patients.

83 The prognostic significance of peripheral blood biomarkers in patients with advanced non-small cell lung cancer treated with pembrolizumab: a clinical study

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A91-A91
Author(s):  
Kira MacDougall ◽  
Muhammad Niazi ◽  
Jeff Hosry ◽  
Sylvester Homsy ◽  
Alexander Bershadskiy
Keyword(s):  
Peripheral Blood ◽  
Lymphocyte Count ◽  
Advanced Nsclc ◽  
Cox Regression ◽  
Absolute Lymphocyte Count ◽  
Blood Biomarkers ◽  
Cox Regression Analysis ◽  
Start Date ◽  
Kaplan Meier ◽  
Significant Difference

BackgroundPembrolizumab is an anti-programmed cell death protein 1 (PD-1) antibody used for the treatment of advanced non-small cell lung carcinoma (NSCLC). Systemic inflammation has long been associated with poor outcomes in many types of solid tumors.1 Peripheral blood biomarkers such as absolute lymphocyte count (ALC) and absolute neutrophil count to absolute lymphocyte count ratio (ANC/ALC) serve as surrogate markers of inflammation. The aim of this study is to investigate ALC and ANC/ALC in patients with advanced NSCLC receiving pembrolizumab and determine if there is a correlation between these biomarkers and overall survival (OS).MethodsA total of 240 patients with advanced NSCLC treated with pembrolizumab at Northwell Health hospital centers were included. The ALC and ANC/ALC were examined at initiation of pembrolizumab and after 6 weeks on treatment. The prognostic role of these peripheral blood biomarkers on OS were examined with Kaplan-Meier curves and a multivariable cox regression analysis.ResultsOf the 240 patients, the majority were male (52%), with a median age of 67 years (interquartile range [IQR] 59–73 years), had a diagnosis of adenocarcinoma (76%), with stage IV disease (82%). PDL-1 expression was >50% in 44% of the patients. The median time on treatment with pembrolizumab was 5.7 months [IQR: 2.7–12.5]. The median ALC and ANC/ALC were significantly lower at 6 weeks of pembrolizumab compared to the start date of treatment (1.38 vs. 1.4, p<0.001) and (3.6 vs. 4.6, p<0.001) respectively. An ALC greater than 1.4 was associated with an increased OS (figure 1), at 6 weeks after initiation of pembrolizumab (p=0.046), but not at the start of treatment (p=0.095). An ANC/ALC less than 5 was associated with improved OS (figure 2), both at initiation of pembrolizumab (p=0.003) and at 6 weeks after initiation of treatment (p = 0.028). Likewise, after adjusting for potential cofounders with a multivariate analysis (table 1), a baseline ANC/ALC of 5 or higher had a significantly increased risk of death (hazards ratio (HR)=1.84; 95% confidence interval (CI), 1.21–2.79; p=0.004), compared with patients with a lower ratio.ConclusionsHigh ALC at time of diagnosis as well as low ANC/ALC at baseline and at 6 weeks on treatment correlated with an increased OS in patients with advanced NSCLC treated with pembrolizumab. These findings represent a readily available predictive biomarker for oncologists and may help with risk stratification and strategizing treatment plans.Abstract 83 Figure 1Kaplan-Meier survival estimates between groups with different ALC at the start date of pembrolizumab and at 6 weeks after initiation of pembrolizumab. There is a statistically significant difference in OS between patients with ALC < 1.4 and patients with ALC ≥ 1.4 at 6 weeks after initiation of pembrolizumab (p = 0.046), but not at the start of treatment (p = 0.095).Abstract 83 Figure 2Kaplan-Meier survival estimates between groups with different ANC/ALC ratio at the start date of pembrolizumab and at 6 weeks after initiation of pembrolizumab. There is a statistically significant difference in OS between patients with ANC/ALC < 5 and patients with ALC ≥ 5, both at the start date of pembrolizumab (p = 0.003) and at 6 weeks after initiation of pembrolizumab (p = 0.028).Abstract 83 Table 1Multivariable cox regression analysis for association of baseline peripheral blood biomarkers and overall survival.Legend: HR, hazards ratio; CI, confidence interval; CNS, central nervous system, ANC/ALC, absolute neutrophil count to absolute lymphocyte count ratio; PDL-1, programmed death-1 ligand 1; ECOG, Eastern Cooperative Oncology Group performance scale.Ethics ApprovalThe study was approved by Zucker School of Medicine at Hofstra/Northwell at Staten Island University Hospital’s IRB #: 19–0922ReferenceMantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–44.

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