Adherence and cumulative bisphosphonate dose in relation to risk of skeletal-related events among older patients with multiple myeloma.

e18250 Background: Adjuvant intravenous bisphosphonates (IV BP) reduce the risk of skeletal-related events (SRE) in patients with multiple myeloma (MM). We examined the effects of bisphosphonate utilization patterns (adherence, cumulative dose and frequency) on risk of SRE. Methods: Patients aged 65 years or older and diagnosed with first primary MM between 2001 and 2011 were identified using the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database. Patients receiving at least one dose of IV BP after MM diagnosis were identified and 5-year SRE-free survival was estimated using the Kaplan-Meier method stratified by demographic groups and compared with the log rank test. Cox proportional hazards models were fit to determine the association between IV BP utilization patterns and SRE after propensity score matching. We investigated the outcome of multiple recurrent SRE using the approach of Andersen-Gill, and estimated subdistribution hazard ratios (SHR) and 95% confidence intervals for risk of first SRE, accounting for death as competing risk. Results: The final cohort included 9176 MM patients with a median age of 76 years. The adjusted 5-year competing-risk SRE model showed a 48% reduction in risk of SRE (95% CI 0.49-0.55) with use of IV BP. In multivariable analyses taking into account competing risks, greater adherence to IV BP, higher cumulative IV BP dose and more frequent administration were all associated with a statistically significant reduction in SRE risks (See Table). Conclusions: Use of IV BP in patients with MM was associated with significant reduction in SRE risk over the 5-year period after MM diagnosis. The effectiveness of IV BP therapy was greater with increasing cumulative dose, adherence to and greater frequency of IV BP administration. [Table: see text]

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Is more aggressive lymph node assessment associated with improved survival in stage II-III colorectal cancer? Evidence from the Surveillance, Epidemiology and End Results (SEER) cancer registry

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.4048 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 4048-4048

Author(s):

Y. Yeh ◽

Q. Cai ◽

J. Chao ◽

M. Russell

Keyword(s):

Colorectal Cancer ◽

Risk Factors ◽

Proportional Hazards ◽

Survival Rates ◽

Cox Proportional Hazards ◽

Stage Ii ◽

Rank Test ◽

Stage Iiia ◽

Nccn Guidelines ◽

Cox Proportional Hazards Models

4048 Background: NCCN guidelines recommend assessment of =12 lymph nodes (LN) to improve accuracy in colorectal cancer (CRC) staging. Previous studies have used various cut-points to assess the relationship between the number of LN sampled and survival. The association between NCCN guideline-compliant nodal sampling and survival is assessed, while controlling for other risk factors. Methods: We selected 145,485 adult patients newly diagnosed with stage II or III from SEER during 1990–2003. Kaplan-Meier curves were compared using the log-rank test. Cox proportional hazards models were constructed to determine the effect of sampling ≥ 12 LN on survival. Results: Median patient follow-up was 5.7 years. The table shows overall survival rates in CRC patients with < 12 versus =12 LN assessed: After adjusting for age, sex, tumor size and grade, sampling ≥ 12 LN was independently associated with improved survival. For patients with =12 versus <12 LN assessed, survival increased by 13% for stage IIa [HR=0.75; 95%CI 0.72–0.78; p< .001], 16% for stage IIb [HR=0.69; 95%CI 0.67- 0.71; p< .001], 12% for stage IIIb [HR=0.75; 95%CI 0.72–0.77], and 10% for stage IIIc [HR=0.85, 95%CI 0.81–0.89]. The association was not statistically significant for stage IIIa patients. Conclusion: Consistent with previous reports, this analysis found that optimal nodal sampling increased survival across stage II and III, specifically when ≥ 12 LN are sampled and when controlling for other risk factors. Furthermore, the results underscore the need for adhering to the NCCN guidelines. The lack of a statistically significant association in stage IIIa patients may be due to small cohort size. [Table: see text] [Table: see text]

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Relationship Between Change in Serum Uric Acid and Ischemic Stroke in Chinese Hypertensive Patients

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.717128 ◽

2021 ◽

Vol 8 ◽

Author(s):

Qiu-hong Tan ◽

Lin Liu ◽

Yu-qing Huang ◽

Yu-ling Yu ◽

Jia-yi Huang ◽

...

Keyword(s):

Uric Acid ◽

Ischemic Stroke ◽

Serum Uric Acid ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Elevated Risk ◽

Rank Test ◽

Hypertensive Patients ◽

Cox Proportional Hazards Models ◽

The Relationship

Background: Limited studies focused on the association between serum uric acid (SUA) change with ischemic stroke, and their results remain controversial. The present study aimed to investigate the relationship between change in SUA with ischemic stroke among hypertensive patients.Method: This was a retrospective cohort study. We recruited adult hypertensive patients who had two consecutive measurements of SUA levels from 2013 to 2014 and reported no history of stroke. Change in SUA was assessed as SUA concentration measured in 2014 minus SUA concentration in 2013. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The Kaplan–Meier analysis and log-rank test were performed to quantify the difference in cumulative event rate. Additionally, subgroup analysis and interaction tests were conducted to investigate heterogeneity.Results: A total of 4,628 hypertensive patients were included, and 93 cases of ischemic stroke occurred during the mean follow-up time of 3.14 years. Participants were categorized into three groups according to their SUA change tertiles [low (SUA decrease substantially): <-32.6 μmol/L; middle (SUA stable): ≥-32.6 μmol/L, <40.2 μmol/L; high (SUA increase substantially): ≥40.2 μmol/L]. In the fully adjusted model, setting the SUA stable group as reference, participants in the SUA increase substantially group had a significantly elevated risk of ischemic stroke [HR (95% CI), 1.76 (1.01, 3.06), P = 0.0451], but for the SUA decrease substantially group, the hazard effect was insignificant [HR (95% CI), 1.31 (0.75, 2.28), P = 0.3353]. Age played an interactive role in the relationship between SUA change and ischemic stroke. Younger participants (age < 65 years) tended to have a higher risk of ischemic stroke when SUA increase substantially.Conclusion: SUA increase substantially was significantly correlated with an elevated risk of ischemic stroke among patients with hypertension.

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Trends in survival and costs among US multiple myeloma patients.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.8046 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 8046-8046

Author(s):

Eric M Maiese ◽

Kristin Evans ◽

Bong-Chul Chu ◽

Debra E. Irwin

Keyword(s):

Multiple Myeloma ◽

Lower Risk ◽

Healthcare Costs ◽

Proportional Hazards ◽

Prediction Method ◽

Cox Proportional Hazards ◽

Risk Of Death ◽

Cox Proportional Hazards Models ◽

Treatment Changes ◽

Time Periods

8046 Background: Survival among multiple myeloma (MM) patients has improved over time, but little is known about concurrent changes in healthcare costs. This study examined trends in both survival and healthcare costs over the same time periods in US MM patients. Methods: The MarketScan Commercial and Medicare claims dataset was used to identify 5199 adult patients diagnosed with MM from Jan. 2006 to Dec. 2014. Patients had no prior evidence of cancer, were continuously enrolled for >12 months prior to MM diagnosis, and were followed through the earliest event (death, end of enrollment, or end of the study period (9/30/2015)). Multivariate GLM and Cox proportional hazards models estimated healthcare costs and survival probabilities, respectively, for two time periods during which patients were diagnosed with MM (2006-2010 vs 2011-2014) while controlling for demographic and clinical characteristics. The recycled prediction method was used to calculate the incremental cost estimates between the time periods. Results: Patients diagnosed in 2011-2014 had a 35% lower risk of death compared to those diagnosed in 2006-2010 (HR [95% CI] = 0.65 [0.57-0.74]. Patients diagnosed in 2011-2014 had 18% (95% CI: 6-31%) higher all cause and 26% (95% CI: 6-50%) higher MM-related per patient per month costs compared to those diagnosed in 2006-2010 (Table). Conclusions: Among MM patients, survival has improved at a greater rate than the increase in healthcare costs. In addition to improvements in MM treatment, changes in overall disease management may have contributed to both the increased expenditures and survival improvements observed in this study. [Table: see text]

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Trends in survival and costs among U.S. patients with multiple myeloma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.8_suppl.12 ◽

2017 ◽

Vol 35 (8_suppl) ◽

pp. 12-12 ◽

Cited By ~ 1

Author(s):

Eric Maiese ◽

Kristin Evans ◽

Bong-Chul Chu ◽

Debra E. Irwin

Keyword(s):

Health Care ◽

Multiple Myeloma ◽

Health Care Costs ◽

Proportional Hazards ◽

Prediction Method ◽

Cox Proportional Hazards ◽

Risk Of Death ◽

Cox Proportional Hazards Models ◽

Time Periods ◽

Care Costs

12 Background: Survival among patients with multiple myeloma (MM)has improved over time, but little is known about concurrent changes in health care costs. This study examined trends in both survival and health care costs over the same time periods in U.S. patients with MM. Methods: The MarketScan Commercial and Medicare claims dataset was used to identify 5199 adult patients diagnosed with MM from Jan. 2006 to Dec. 2014. Patients had no prior evidence of cancer, were continuously enrolled for ≥ 12 months prior to MM diagnosis, and were followed through the earliest event (death, end of enrollment, or end of the study period (9/30/2015)). Multivariate GLM and Cox proportional hazards models estimated health care costs and survival probabilities, respectively, for two time periods during which patients were diagnosed with MM (2006-2010 vs. 2011-2014) while controlling for demographic and clinical characteristics. The recycled prediction method was used to calculate the incremental cost estimates between the time periods. Results: Patients diagnosed in 2011-2014 had a 35% lower risk of death compared to those diagnosed in 2006-2010 (HR [95% CI] = 0.65 [0.57-0.74]). Patients diagnosed in 2011-2014 had 18% (95% CI: 6-31%) higher all cause and 26% (95% CI: 6-50%) higher MM-related per patient per month costs compared to those diagnosed in 2006-2010 (see table). Conclusions: Among patients with MM, survival has improved at a greater rate than the increase in health care costs. In addition to improvements in MM treatment, changes in overall disease management may have contributed to both the increased expenditures and survival improvements observed in this study.[Table: see text]

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Impact of clinical and pathological variables on stage I non-small cell lung cancer outcomes.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21071 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21071-e21071

Author(s):

Matthew C Lee ◽

Dimitre C Stefanov ◽

Mallorie B Angert ◽

Erica C Cohn ◽

Nina Kohn ◽

...

Keyword(s):

Proportional Hazards ◽

Cox Regression ◽

Neuroendocrine Differentiation ◽

Clinical Importance ◽

Recurrence Risk ◽

Cox Proportional Hazards ◽

Stage I ◽

Rank Test ◽

Histological Features ◽

Cox Proportional Hazards Models

e21071 Background: Stage I patients (pts) have 5-year survival ranging 50-75% suggesting heterogeneity within. While American Joint Committee on Cancer 8th edition upstages tumors with visceral pleural invasion (VPI) to IB, other histological features namely lymphovascular invasion (LVI), micropapillary pattern (MIP), spread through airspace (STAS) & neuroendocrine differentiation (NE) may also affect prognosis. This retrospective single institution study evaluated influence of these factors along with pt variables age, gender, smoking, Charleston comorbidity index (CCI) & chemotherapy (CT) on recurrence & mortality. Methods: 351 resected stage I cases from 2015-2019 were included. Data was summarized as means (standard deviation/SD) or percentages. Association between variables & outcomes (measured from diagnosis till event or last visit if no event) were investigated using Univariate & Multiple Cox proportional hazards models. Survival curves were compared using the Log-Rank test when the assumption for the proportional hazards was not satisfied. All predictors were included in the multiple Cox regression models based on their clinical importance. P < 0.05 was considered statistically significant. SAS 9.4 (SAS Institute, Cary, NC) was used for the analysis. Results: Mean age was 69.62 years (9.83). Majority were female (57.3%), smokers (76.9%), & had adenocarcinoma (AC) (78.6%). 39% had COPD & mean CCI was 6.3 (1.74). 193 (55%) pts had lobectomy or larger procedure while 158 (45%) had sub-lobar resection. 45 (12.8%) pts received CT. Recurrence & death occurred in 33 (9.4%) & 15 (4.3%) pts respectively. Univariate models indicated higher recurrence risk with NE (HR = 4.18 95% CI 1.47-11.9, p = 0.0075), LVI (HR = 2.68, 95% CI 1.03-6.94, p = 0.0423), COPD (HR = 3.28 95% CI 1.56-6.9, p = 0.0017), age (HR = 1.05 95% CI 1.01-1.09, p = 0.0212), & CCI (HR = 1.57 95% CI 1.35-1.83, p < .0001). CT was also associated with increased recurrence risk (HR = 8.61, 95% CI 4.28-17.33, p < .0001). Multivariable model for recurrence retained significance for CT & CCI. Age (HR = 1.07 95% CI 1.01-1.14, p = 0.0312), CCI (HR = 1.27 95 % CI 1.02-1.59, p = 0.0347) were associated with mortality in univariate models. Multivariate analysis for mortality wasn’t feasible due to few events. Conclusions: Histological features other than VPI may be associated with recurrence. Pts who received CT had increased recurrence but they possibly had multiple risk factors or other adverse features not assessed here. Limitations included retrospective nature, limited sample size & small number of events.

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Alternating combination VCMP/VBAP chemotherapy versus melphalan/prednisone in the treatment of multiple myeloma: a randomized multicentric study of 487 patients.

Journal of Clinical Oncology ◽

10.1200/jco.1993.11.6.1165 ◽

1993 ◽

Vol 11 (6) ◽

pp. 1165-1171 ◽

Cited By ~ 37

Author(s):

J Bladé ◽

J F San Miguel ◽

A Alcalá ◽

J Maldonado ◽

M A Sanz ◽

...

Keyword(s):

Multiple Myeloma ◽

Partial Response ◽

Combination Chemotherapy ◽

Proportional Hazards ◽

Response Rate ◽

Objective Response ◽

Survival Rates ◽

Cox Proportional Hazards ◽

Multicentric Study ◽

Cox Proportional Hazards Models

PURPOSE To determine whether combination chemotherapy with alternating cycles of vincristine, cyclophosphamide, melphalan, and prednisone (VCMP) and vincristine, carmustine (BCNU), Adriamycin (doxorubicin; Farmitalia, Carlo-Erba Laboratories, Spain), and prednisone (VBAP) is better than the standard melphalan-prednisone (MP) regimen in multiple myeloma (MM). PATIENTS AND METHODS From January 1985 to December 1989, 28 institutions of the Spanish Cooperative Group for Hematological Malignancies Treatment, Spanish Society of Hematology (PETHEMA) entered 487 eligible patients with symptomatic MM into the study. Patients were randomized to receive either MP or alternating courses of VCMP and VBAP. Logistic regression and the Cox proportional hazards models were used to assess the association between patients' characteristics and response rate and survival, respectively. RESULTS Among 449 patients who were assessable for response, the overall response rate to MP was 51.8% (31.5% objective response plus 20.3% partial response) as compared with 62.7% (45.2% objective response plus 17.5% partial response) to VCMP/VBAP (P = .025). Also, a significantly higher proportion of objective responses was observed with combination chemotherapy (45.2% v 31.5%; P = .004). The factors associated with an unfavorable response rate in the overall series were low platelet count, treatment with MP, high creatinine level and immunoglobulin, (IgG) monoclonal (M)-component. No significant differences were found when survival rates of both groups of patients were compared. However, patients with IgA myeloma treated with VCMP/VBAP survived significantly longer than those who received MP (median, 20.2 v 38.4 months; P < .005). CONCLUSION These results indicate that combination chemotherapy improves response rate in MM. However, this does not result in a significantly different survival rate, except for patients with IgA myeloma, who survive significantly longer with combination chemotherapy.

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Impact of time-varying cumulative bevacizumab exposures on survival: re-analysis of data from randomized clinical trial in patients with metastatic colo-rectal cancer

BMC Medical Research Methodology ◽

10.1186/s12874-020-01202-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Adrien Guilloteau ◽

Michal Abrahamowicz ◽

Olayide Boussari ◽

Valérie Jooste ◽

Thomas Aparicio ◽

...

Keyword(s):

Drug Use ◽

Cumulative Dose ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Cumulative Effects ◽

Cumulative Exposure ◽

Time Varying ◽

Protective Effects ◽

Cox Proportional Hazards Models ◽

Exposure Metrics

Abstract Background As cancer treatment, biotherapies can be as effective as chemotherapy while reducing the risk of secondary effects, so that they can be taken over longer periods than conventional chemotherapy. Thus, some trials aimed at assessing the benefit of maintaining biotherapies during chemotherapy-free intervals (CFI). For example, the recent PRODIGE9 trial assessed the effect of maintaining bevacizumab during CFI in metastatic colorectal cancer (mCRC) patients. However, its analysis was hindered by a small difference of exposure to the treatment between the randomized groups and by a large proportion of early drop outs, leading to a potentially unbalanced distribution of confounding factors among the trial completers. To address these limitations, we re-analyzed the PRODIGE9 data to assess the effects of different exposure metrics on all-cause mortality of patients with mCRC using methods originally developed for observational studies. Methods To account for the actual patterns of drug use by individual patients and for possible cumulative effects, we used five alternative time-varying exposure metrics: (i) cumulative dose, (ii) quantiles of the cumulative dose, (iii) standardized cumulative dose, (iv) Theoretical Blood Concentration (TBC), and (v) Weighted Cumulative Exposure (WCE). The last two metrics account for the timing of drug use. Treatment effects were estimated using adjusted Hazard Ratio from multivariable Cox proportional hazards models. Results After excluding 112 patients who died during the induction period, we analyzed data on 382 patients, among whom 320 (83.8%) died. All time-varying exposures improved substantially the model’s fit to data, relative to using only the time-invariant randomization group. All exposures indicated a protective effect for higher cumulative bevacizumab doses. The best-fitting WCE and TBC models accounted for both the cumulative effects and the different impact of doses taken at different times. Conclusions All time-varying analyses, regardless of the exposure metric used, consistently suggested protective effects of higher cumulative bevacizumab doses. However, the results may partly reflect the presence of a confusion bias. Complementing the main ITT analysis of maintenance trials with an analysis of potential cumulative effects of treatment actually taken can provide new insights, but the results must be interpreted with caution because they do not benefit from the randomization. Trial registration clinicaltrials.gov, NCT00952029. Registered 8 August 2009.

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Is neoadjuvant (neoadj) treatment necessary prior to liver resection in patients with resectable liver metastases (mets) from colorectal carcinoma (CRC) treated with post-resection hepatic arterial infusion (HAI) plus systemic (SYS) chemotherapy

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.14503 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 14503-14503 ◽

Cited By ~ 2

Author(s):

N. E. Kemeny ◽

M. Capanu ◽

F. Huitzil-Melendez ◽

D. Haviland ◽

Y. Fong ◽

...

Keyword(s):

Liver Resection ◽

Proportional Hazards ◽

Disease Free Survival ◽

Hepatic Arterial Infusion ◽

Cox Proportional Hazards ◽

Rank Test ◽

Test Results ◽

Cox Proportional Hazards Models ◽

Resection Margin Status ◽

Improvement In Survival

14503 Background: Neoadjuvant therapy in patients (pts) with resectable liver mets has been reported to be associated with improved survival. We evaluated the clinical benefit of neoadj therapy in our pts receiving HAI + SYS after liver resection. Methods: In 4 studies of HAI + SYS after resection of CRC mets, data on neoadj, age, gender, clinical risk score (CRS), number of mets, primary site, resection margin status, presence of synchronous primary and/or bilobar disease were analyzed. Univariate and multivariate Cox proportional hazards models were used to examine differences in overall survival, hepatic or extrahepatic disease-free survival (DFS) between pts who received vs pts who did not receive neoadj. Differences among subgroups were compared using the log-rank test. Results: 234 pts from 4 post-liver resection trials using HAI + SYS were included. Each trial used HAI floxuridine/dexamethasone, with differing SYS regimens: FU/LV (n = 74); CPT11 (n = 98); FOLFOX (n = 31); and FOLFOX or FOLFIRI, ± bevacizumab (n = 31). Neoadj was given to 28% of the pts. Median followup was 4.6 years. No differences in terms of survival, hepatic or extrahepatic DFS were noted between pts who did or did not receive neoadj. Multivariate analyses showed no survival advantage for pts who received neoadj (Y vs N) (HR 0.997, 95% CI, 0.56–1.78). No subsets of pts were identified that showed an improvement in survival from neoadj (table), including pts who responded to neoadj prior to liver resection. Conclusions: Our results do not appear to support the use of neoadj in pts with resectable liver mets from CRC, if they are to be treated with postoperative HAI and SYS chemotherapy. [Table: see text] No significant financial relationships to disclose.

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CMET-12. EFFICACY OF UPFRONT IMMUNE CHECKPOINT INHIBITORS IN LUNG CANCER BRAIN METASTASIS

Neuro-Oncology ◽

10.1093/neuonc/noz175.213 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi53-vi53

Author(s):

Addison Barnett ◽

Adam Lauko ◽

Hong Li ◽

Assad Ali ◽

Soumya Sagar ◽

...

Keyword(s):

Lung Cancer ◽

Brain Metastasis ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Proportional Hazards ◽

Checkpoint Inhibitors ◽

Tertiary Care ◽

Cox Proportional Hazards ◽

Rank Test ◽

Cox Proportional Hazards Models

Abstract INTRO/OBJECTIVE Immune checkpoint inhibitors (ICI) have improved outcomes in a subset of patients with lung cancer. However, data describing the efficacy of ICI in lung cancer brain metastasis (LCBM) is limited. We analyzed overall survival (OS) in patients with LCBM treated with upfront ICI, defined as having received ICI within 90-days of LCBM diagnosis, compared to non-ICI therapies. METHODS We reviewed 665 patients with LCBM diagnosed between 2000 and 2018 at a major tertiary care institution. Of those patients, 240 received ICI, 164 of which received ICI after 90-days and 76 received ICI within 90-days. Propensity score (PS) was calculated by logistic regression model including age, KPS, number of baseline brain lesions, and presence of extra-cranial metastasis (ECM) at time of LCBM diagnosis. OS from LCBM diagnosis between PS matched cohorts were compared using Kaplan-Meier, the Log-Rank test, and Cox proportional hazards models. RESULTS Prior to PS matching, median survival between ICI and non-ICI cohorts was not significantly different (10.9 months for both, p=0.81), although more ICI patients had ECM (57.1% vs 40.9%, p=0.006). Following PS matching, the ICI (n=76) and non-ICI (n=76) cohorts had median age (62.4 vs 62.3 years), KPS (80 for both), lesion number (2 for both), and ECM (56.6% for both). Of matched patients, 94% received SRS, 52% received WBRT, and 29% underwent surgical resection. Compared to non-ICI, the ICI cohort had a 2-year OS hazard ratio=0.87 (95% CI=0.58–1.31, p=0.51). Median and 1-year survival were not significantly different between ICI and non-ICI cohorts (median: 10.9 vs 9.1 months; 1-yr: 43.0% vs 42.4%). CONCLUSION Patients with LCBM who received ICI within 90-days of their diagnosis did not have improvement in OS compared to patients who received non-ICI therapies. Evaluation of clinical factors that may affect the efficacy and durability of immunotherapy is ongoing and will be presented.

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Clinical outcomes in patients with metastatic renal cell carcinoma receiving everolimus or temsirolimus after sunitinib.

Canadian Urological Association Journal ◽

10.5489/cuaj.1604 ◽

2014 ◽

Vol 8 (3-4) ◽

pp. 121 ◽

Cited By ~ 7

Author(s):

Roberto Iacovelli ◽

Giacomo Cartenì ◽

Michele Milella ◽

Rossana Berardi ◽

Giuseppe Di Lorenzo ◽

...

Keyword(s):

Proportional Hazards ◽

Kinase Inhibitor ◽

Multivariable Analysis ◽

Progression Free Survival ◽

Cox Proportional Hazards ◽

Rank Test ◽

Clinical Activity ◽

Second Line ◽

Cox Proportional Hazards Models ◽

Line Setting

Introduction: There are little data on the clinical activity of temsirolimus (TM) and everolimus (EV) when used as second-line therapy after sunitinib (SU) in patients with metastatic renal cellcarcinoma (mRCC).Methods: Patients with mRCC treated with EV or TM after SU were included in this retrospective analysis. Progression-free survival (PFS), time to sequence failure (TTSF) from the start of SU to disease progression with EV/TM and overall survival (OS) were estimated using Kaplan-Meier method and compared across groups using the log-rank test. Cox proportional hazards models were applied to investigate predictors of TTSF and OS.Results: In total, 89 patients (median age 60.0 years) were included. At baseline 43% were classified as MSKCC good-risk, 43% as intermediate-risk and 14% as poor-risk. Median OS was 36.3 months and median TTSF was 17.2 months. Sixty-five patients received SU-EV and 24 patients SU-TM. Median PFS after the second-line treatment was 4.3 months in the EV group and 3.5 months in the TM group (p = 0.63). Median TTSF was 17.0 and 18.9 months (p = 0.32) and the OS was 35.8 and 38.3 months (p = 0.73) with SU-EV and SU-TM, respectively. The prognostic role of initial MSKCC was confirmed by multivariable analysis (hazard ratio 1.76, 95% confidence interval 1.08-2.85. p = 0.023).Conclusions: This study did not show significant differences in terms of disease control and OS between EV and TM in the second-line setting. EV remains the preferred mTOR inhibitor for the treatment of mRCC patients resistant to prior tyrosine kinase inhibitor treatment.

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