Erlotinib after initial platinum-doublet chemotherapy in patients with epidermal growth factor receptor (EGFR) wild-type (WT) non-small cell lung cancer (NSCLC): Results of a combined patient-level analysis of the BR.21 and SATURN trials.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8080-8080 ◽  
Author(s):  
Raymond U Osarogiagbon ◽  
Federico Cappuzzo ◽  
Tudor-Eliade Ciuleanu ◽  
Larry Leon
Keyword(s):  
Egfr Mutation ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Sensitivity Analyses ◽  
Egfr Mutations ◽  
Rank Test ◽  
Double Blind ◽  
Mutation Status ◽  
The Impact

8080 Background: Two double-blind, prospective, randomized, placebo-controlled trials demonstrated survival benefit in unselected populations with advanced NSCLC in the 2nd/3rd line (BR.21) and maintenance setting (SATURN). The efficacy of erlotinib in patients with EGFR WT NSCLC has been questioned. We examined the impact of erlotinib vs placebo in confirmed EGFR WT patients in both studies. Methods: Combined re-analysis of progression-free survival (PFS) (from date of randomization to investigator-assessed progression or death from any cause), and overall survival (OS) (from date of randomization to death from any cause) in patients with known WT EGFR. PFS and OS were estimated by Kaplan-Meier curves and compared by 2-sided log-rank test. Cox proportional hazards model was used to estimate hazard ratios (HR) adjusted for potential confounders. Sensitivity analyses assessed comparability of patients with known and unknown EGFR mutation status to determine generalizability of the two study populations. Results: 74% of the BR.21 population (n=150) and 89% of the SATURN population (n=388) with known EGFR mutation status had WT EGFR. PFS and OS for individual and combined analyses are shown (Table). Adjusting for non-randomized therapy after study therapy discontinuation, HR for OS was 0.74 (0.61–0.91); p<0.01. Baseline characteristics were similar for patients with known and unknown EGFR status, suggesting generalizability of the EGFR WT data. Erlotinib benefit was sustained in all clinical subsets. Conclusions: Erlotinib provided a consistent and significant improvement in survival for patients with EGFR WT NSCLC in both studies, individually and in combination. The benefit of erlotinib does not appear to be limited to patients with activating EGFR mutations. [Table: see text]

Pretreatment neutrophil/lymphocyte ratio (NLR) prior to steroids as a prognostic factor in metastatic castrate refractory prostate cancer (mCRPC) patients treated with taxanes.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 273-273
Author(s):  
David Chan ◽  
Jennifer Mary McLachlan ◽  
Megan Crumbaker ◽  
Gavin M. Marx
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Sensitivity Analyses ◽  
Rank Test ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio

273 Background: The neutrophil/lymphocyte ratio (NLR) has been demonstrated to be a prognostic factor in multiple malignancies. Prior analyses have demonstrated conflicting results in correlation between NLR and overall survival (OS) in mCRPC. Prednisone and dexamethasone, commonly used in chemotherapy regimens for prostate cancer, have been demonstrated to affect neutrophils and hence NLR. We investigated the correlation between pre-dexamethasone NLR and OS in patients with mCRPC. Methods: We performed a retrospective single-center study of patients with mCRPC who received taxane-based chemotherapy (docetaxel or cabazitaxel) between 9/2005 and 12/2012. Patients were included if blood test results were available between 3 and 28 days prior to commencement of chemotherapy. Baseline demographics and NLR were correlated with OS using a Cox proportional hazards model. Results: 42 patients were included, 9 of whom were still alive, with median age 70 and median follow-up 23.1 months. Median OS was 24.1 months. 36 were commenced on docetaxel-based chemotherapy and 6 on cabazitaxel-based chemotherapy. Considering NLR as a categorical variable, OS was significantly better in patients with NLR<5 (n=28) compared to those with NLR>5 (n=14), with median OS 32mo vs 15.4mo and HR 2.155 (95% CI 1.072-4.332, p=0.0007 by log-rank test). In multivariate analyses, NLR (p=0.008) and age (p=0.048) were independent predictors of overall survival. In sensitivity analyses, when including NLRs within 48 hours of chemotherapy initiation, the correlation between NLR and OS was only marginally significant (p=0.048). Conclusions: HighNLR is an adverse prognostic marker for decreased overall survival in mCRPC patients undergoing taxane-based chemotherapy. Previous conflicting results regarding its value may be related to the effect of steroids on NLR.

Exploratory analysis of left- versus right-sided colorectal carcinoma in RAISE: A randomized, double-blind, phase 3 trial of ramucirumab (RAM) + FOLFIRI versus placebo (PBO) + FOLFIRI.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 668-668 ◽  
Author(s):  
David Craig Portnoy ◽  
Radka Obermannova ◽  
Gyorgy Bodoky ◽  
Jana Prausová ◽  
Rocio Garcia-Carbonero ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Proportional Hazards Model ◽  
Tumor Location ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Double Blind ◽  
Model Estimate ◽  
Primary Tumor Site ◽  
Primary Tumor Location

668 Background: Ramucirumab is a human IgG1 monoclonal antibody antagonist of VEGFR-2. Overall survival (OS) and progression-free survival (PFS) in 2nd line FOLFIRI based treatment for metastatic colorectal cancer (mCRC) were improved with RAM therapy versus PBO in the RAISE trial. Recent work suggests mCRC primary tumor location is both prognostic and predictive; with improved OS and therapy-specific sensitivity observed in left (L)- vs right (R)-sided tumors. Given these findings, the RAISE trial data was subjected to post-hoc analysis to determine if sidedness influenced RAM efficacy. Methods: Primary tumor site was obtained. L-CRC was defined as the splenic flexure, descending and sigmoid colon, and rectum, while R-CRC included transverse, ascending colon and cecum. OS/PFS in L and R subgroups were analyzed via Kaplan-Meier method and unstratified log-rank test (treatments within subgroup), unstratified Cox proportional hazards model (estimate hazard ratio [HR] and 95% CI), and Wald test (treatment-by-subgroup interaction). Results: Tumor location was available for 1012/1072 (94%) patients, 699 L- and 313 R-CRC. Baseline characteristics were balanced between arms. RAM treatment enhanced L-CRC median OS by 2.5 mo (median 14.5 vs 12.0 mo) with a HR (95% CI) = 0.807 (0.675, 0.965), P = 0.019; compared to a 1.1 mo increase in median OS in R-CRC vs PBO (12.7 vs 11.6) with a HR (95% CI) = 0.971 (0.750, 1.258), P = 0.823; and, RAM enhanced L-CRC median PFS by 1.6 mo (6.0 vs 4.4 mo) and HR (95% CI) = 0.776 (0.664, 0.906), P = 0.001 compared to a 1.1 mo increase in median PFS R-CRC vs PBO (5.6 vs 4.5) with a HR (95% CI) = 0.855 (0.674, 1.084), P = 0.197. The treatment-by-subgroup interaction for both OS and PFS was not significant ( P = 0.276, 0.578, respectively). Conclusions: Despite L-CRC patients having longer OS/PFS and a seemingly stronger RAM treatment effect than R-CRC, the non-significant interaction test cannot verify sidedness as being predictive of RAM efficacy. The current study confirms ramucirumab benefits mCRC patients regardless primary tumor location. Clinical trial information: NCT01183780.

Placebo controlled, double blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors (PROMID): Results on long-term survival.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4030-4030 ◽  
Author(s):  
Rudolf Arnold ◽  
Michael Wittenberg ◽  
Anja Rinke ◽  
Carmen Schade-Brittinger ◽  
Behnaz Aminossadati ◽  
...  
Keyword(s):  
Cause Of Death ◽  
Proportional Hazards Model ◽  
Randomized Study ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Study Entry ◽  
Rank Test ◽  
Double Blind ◽  
Term Survival ◽  
Octreotide Lar

4030 Background: Octreotide LAR (O) compared to placebo (P) lengthens significantly time to tumor progression (TTP) in patients with metastatic midgut neuroendocrine tumors (Rinke et al. 2009). The antiproliferative response was more pronounced in patients with low (≤ 10%) hepatic tumor load (HL). To investigate whether this beneficial effect also affects overall survival (OS), patients included in the PROMID trial were followed until January 2013 at least once a year. Methods: Between July 2001 and January 2008, 42 and 43 patients were randomly assigned to receive O or P. Post study treatment was at the discretion of the local investigator. Data on cause of death and on post study treatment were documented. OS was analyzed using the Kaplan-Meier method. Treatment groups (O vs. P; HL at study entry ≤ 10% vs. >10%) were compared using the log rank test and hazard ratios were estimated with the use of the Cox proportional hazards model. Results: 41 of 85 patients died until January 2013. 19 in the octreotide and 22 in the placebo arm. Median OS for all 85 patients was 85 months, “not reached” in the O arm and 84 months in the P arm (p=0.59, HR=0.85 [CI 0.46; 1.56]). Cause of death was unrelated to the tumor disease in 8 patients. 26 of 64 patients (10 in the O vs. 16 in the P arm) died in the HL ≤ 10% subgroup and 15 of 21 patients (9 in the O vs. 6 in the P arm) in the HL > 10 % (p=0.002, HR=2.7). Median OS in the HL ≤ 10% subgroup was “not reached” (octreotide) vs 80.5 months (placebo) (p=0.14, HR=0.56 [CI 0.25; 1.23]). In the HL > 10% subgroup the respective numbers were 35 vs. 84 months (p=0.14, HR=2.18 [CI 0.75; 6.33]). Post study treatment in the O and P groups included octreotide LAR (29 vs. 38 patients), hepatic CHE (5 vs. 12 patients), PRRT (13 vs. 13 patients) and CHT (4 vs. 5 patients). Conclusions: Octreotide LAR not only prolongs TTP but also extends OS in the subgroup of patients with metastatic midgut NETs and a low HL (≤ 10% at study entry) but not in the high (HL > 10%) subgroup. Almost all patients who were randomized at study entry in the P group received octreotide LAR after disease progression, but these experienced a less favourable OS in the low HL subgroup. Clinical trial information: NCT00171873.

scholarly journals Effect of Leptin Therapy on Survival in Generalized and Partial Lipodystrophy: A Matched Cohort Analysis

2021 ◽  
Author(s):  
Keziah Cook ◽  
Omer Ali ◽  
Baris Akinci ◽  
Maria Cristina Foss de Freitas ◽  
Renan Magalhães Montenegro ◽  
...  
Keyword(s):  
Mortality Risk ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cohort Analysis ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Sensitivity Analyses ◽  
Naive Patient ◽  
Partial Lipodystrophy ◽  
The Impact

Abstract Context Data quantifying the impact of metreleptin therapy on survival in nonHIVrelated generalized lipodystrophy (GL) and partial lipodystrophy (PL) are unavailable. Objective This study aimed to estimate the treatment effect of metreleptin on survival in patients with GL and PL. Design/Setting/Patients Demographic and clinical characteristics were used to match metreleptin-treated and metreleptin-naïve patients with GL and PL. Differences in mortality risk were estimated between matched cohorts of metreleptin-treated and metreleptin-naïve patient cohorts using Cox proportional hazard models. Sensitivity analyses assessed the impact of study assumptions and robustness of results. Outcome Measures This study assessed time to mortality and risk of mortality. Results The analysis evaluated 103 metreleptin-naïve patients with characteristics matched to 103 metreleptin-treated patients at treatment initiation. Even after matching, some metabolic and organ abnormalities were more prevalent in the metreleptin-treated cohort due to bias toward treating more severely affected patients. A Cox proportional hazards model associated metreleptin therapy with an estimated 65% decrease in mortality risk (HR 0.348, 95% CI: 0.134-0.900; P = 0.029) even though the actual number of events were relatively small. Results were robust across a broad range of alternate methodological assumptions. Kaplan-Meier estimates of time to mortality for the metreleptin-treated and the matched metreleptin-naïve cohorts were comparable. Conclusions Metreleptin therapy was associated with a reduction in mortality risk in patients with lipodystrophy syndromes despite greater disease severity in treated patients, supporting the view that metreleptin can have a positive disease-modifying impact. Confirmatory studies in additional real-world and clinical datasets are warranted.

Real-world outcomes of patients with advanced non-small cell lung cancer (aNSCLC) and autoimmune disease (AD) receiving immune checkpoint inhibitors (ICIs).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 110-110 ◽  
Author(s):  
Sean Khozin ◽  
Mark S. Walker ◽  
Monika Jun ◽  
Li Chen ◽  
Edward Stepanski ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Real World ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
The Impact

110 Background: Anecdotal and early evidence suggest ICIs are being used in patients with advanced malignancies and history of AD, despite such patients being typically excluded from traditional clinical trials. We compared the outcomes of patients with or without AD, all of whom had ICI treatment for aNSCLC. Methods: We conducted a retrospective, observational cohort study using de-identified, curated data in ASCO’s CancerLinQ. Patients with Stage III or IV NSCLC who received ≥1 dose of an ICI and had ≥2 visits from Jan 2011 to Nov 2018 were included. AD status prior to ICI treatment was identified using ICD-9/ICD-10 codes or AD medications (including steroids). Symphony claims data were linked via tokenization to build cohorts. Time to treatment discontinuation (TTD), time to next treatment (TTNT), real-world progression-free survival (rwPFS) and overall survival (OS) were compared across the two cohorts using the log-rank test. Cox Proportional Hazards Model was used to adjust for covariates. Adverse events (AEs) were compared using Chi-Square and Fisher’s Exact Test. Active AD was defined as evidence of autoimmune disease in the year prior to starting ICIs. Results: Among 2425 patients with aNSCLC treated with ICIs, AD was present in 22% (N=538). Median OS in all patients was 12.4 months (95% CI 11.3-13.5). TTD, TTNT, rwPFS and OS did not differ between the two cohorts (Table). There was no association between AD status and outcomes. There was no increased incidence of AEs in the AD group; however a sub-analysis among patients with active AD showed higher rates of select AEs including endocrine, GI and blood disorders. Conclusions: This analysis demonstrates that patients with evidence of AD prior to receiving ICI have similar outcomes compared to patients with no evidence of AD. Further research is needed to better understand the impact of active AD on the risk of AEs and patient outcomes. [Table: see text]

Age at Exposure to Parental Suicide and the Subsequent Risk of Suicide in Young People

Crisis ◽  
2018 ◽  
Vol 39 (1) ◽  
pp. 27-36 ◽  
Author(s):  
Kuan-Ying Lee ◽  
Chung-Yi Li ◽  
Kun-Chia Chang ◽  
Tsung-Hsueh Lu ◽  
Ying-Yeh Chen
Keyword(s):  
Young People ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Birth Registry ◽  
Data Set ◽  
Parental Suicide ◽  
The Impact ◽  
Age At Exposure

Abstract. Background: We investigated the age at exposure to parental suicide and the risk of subsequent suicide completion in young people. The impact of parental and offspring sex was also examined. Method: Using a cohort study design, we linked Taiwan's Birth Registry (1978–1997) with Taiwan's Death Registry (1985–2009) and identified 40,249 children who had experienced maternal suicide (n = 14,431), paternal suicide (n = 26,887), or the suicide of both parents (n = 281). Each exposed child was matched to 10 children of the same sex and birth year whose parents were still alive. This yielded a total of 398,081 children for our non-exposed cohort. A Cox proportional hazards model was used to compare the suicide risk of the exposed and non-exposed groups. Results: Compared with the non-exposed group, offspring who were exposed to parental suicide were 3.91 times (95% confidence interval [CI] = 3.10–4.92 more likely to die by suicide after adjusting for baseline characteristics. The risk of suicide seemed to be lower in older male offspring (HR = 3.94, 95% CI = 2.57–6.06), but higher in older female offspring (HR = 5.30, 95% CI = 3.05–9.22). Stratified analyses based on parental sex revealed similar patterns as the combined analysis. Limitations: As only register-­based data were used, we were not able to explore the impact of variables not contained in the data set, such as the role of mental illness. Conclusion: Our findings suggest a prominent elevation in the risk of suicide among offspring who lost their parents to suicide. The risk elevation differed according to the sex of the afflicted offspring as well as to their age at exposure.

scholarly journals The correlation between gain of chromosome 8q and survival in patients with clear and papillary renal cell carcinoma

2017 ◽  
Vol 10 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Reza Mehrazin ◽  
Essel Dulaimi ◽  
Robert G. Uzzo ◽  
Karthik Devarjan ◽  
Jianming Pei ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cytogenetic Analysis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Renal Tumors ◽  
Rank Test

Background: The proto-oncogene c-MYC, located on chromosome 8q, can be upregulated through gain of 8q, causing alteration in biology of renal cell carcinoma (RCC). The aim of this study was to evaluate the prevalence of c-MYC through chromosome 8q gain and to correlate findings with cancer-specific mortality (CSM), and overall survival (OS). Methods: Cytogenetic analysis by conventional or Chromosomal Genomic Microarray Analysis (CMA) was performed on 414 renal tumors. Nonclear and nonpapillary RCC were excluded. Impact of gain in chromosome 8q status on CSM, OS, and its correlation with clinicopathological variables were evaluated. CSM and OS were assessed using log-rank test and the Cox proportional hazards model. Results: A total of 297 RCC tumors with cytogenetic analysis were included. Gain of 8q was detected in 18 (6.1%) tumors (9 clear cell and 9 papillary RCC), using conventional method ( n = 11) or CMA ( n = 7). Gain of 8q was associated with higher T stage ( p < 0.001), grade ( p < 0.001), nodal involvement ( p = 0.005), and distant metastasis ( p < 0.001). No association between gain of 8q and age ( p = 0.23), sex ( p = 0.46), and Charlson comorbidity index (CCI, p = 0.59) were seen. Gain of 8q was associated with an 8.38-fold [95% confidence interval (CI), 3.83–18.34, p < 0.001] and 3.31-fold (95% CI, 1.56–7.04, p = 0.001) increase in CSM and decrease in OS, respectively, at a median follow up of 56 months. Conclusion: Chromosome 8q harbors the proto-oncogene c-MYC, which can be upregulated by gain of 8q. Our findings suggest that gain of 8q, can predict aggressive tumor phenotype and inferior survival in RCC.

scholarly journals Blood eosinophils on hospital admission for COPD exacerbation do not predict the recurrence of moderate and severe relapses

2021 ◽  
Vol 7 (1) ◽  
pp. 00543-2020
Author(s):  
Balázs Csoma ◽  
András Bikov ◽  
Ferenc Tóth ◽  
György Losonczy ◽  
Veronika Müller ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Forced Expiratory Volume ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Full Blood Count ◽  
Rank Test ◽  
Severe Exacerbation ◽  
Increased Risk ◽  
Exacerbation Of Copd

Background and objectiveThe relationship between hospitalisation with an eosinophilic acute exacerbation of COPD (AE-COPD) and future relapses is unclear. We aimed to explore this association by following 152 patients for 12 months after hospital discharge or until their first moderate or severe flare-up.MethodsPatients hospitalised with AE-COPD were divided into eosinophilic and non-eosinophilic groups based on full blood count results on admission. All patients were treated with a course of systemic corticosteroid. The Cox proportional hazards model was used to study the association with the time to first re-exacerbation; a generalised linear regression model was applied to identify clinical variables related to the recurrence of relapses.ResultsWe did not find a difference in the time to the next moderate or severe exacerbation between the eosinophilic (≥2% of total leukocytes and/or ≥200 eosinophils·µL−1, n=51, median (interquartile range): 21 (10–36) weeks) and non-eosinophilic groups (n=101, 17 (9–36) weeks, log-rank test: p=0.63). No association was found when other cut-off values (≥3% of total leukocytes and/or ≥300 eosinophils·µL−1) were used for the eosinophilic phenotype. However, the higher number of past severe exacerbations, a lower forced expiratory volume in 1 s (FEV1) at discharge and higher pack-years were related to shorter exacerbation-free time. According to a subgroup analysis (n=73), 48.1% of patients with initial eosinophilic exacerbations had non-eosinophilic relapses on readmission.ConclusionsOur data do not support an increased risk of earlier recurring moderate or severe relapses in patients hospitalised with eosinophilic exacerbations of COPD. Eosinophilic severe exacerbations present a variable phenotype.

Treatment of metastatic disease with immune checkpoint inhibitors nivolumab and pembrolizumab: Effect of performance status on clinical outcomes.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18689-e18689
Author(s):  
Leah Wells ◽  
Michael Cerniglia ◽  
Audrey C. Jost ◽  
Gregory Joseph Britt
Keyword(s):  
Disease Control ◽  
Proportional Hazards Model ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Time To Death ◽  
Significant Difference ◽  
Line Of Therapy

e18689 Background: While guidelines exist for appropriate use of chemotherapy in the metastatic setting based on performance status, such recommendations are less readily available for immune checkpoint inhibitors (ICIs). We sought to determine if there is a relationship between Eastern Cooperative Oncology Group (ECOG) performance status and outcomes on immunotherapy in patients treated for metastatic disease at our community-based oncology practice. Methods: 253 patients were identified as receiving nivolumab or pembrolizumab for stage IV malignancy at Cancer Centers of Colorado-SCL Health, between June 2018 and November 2020. Patients initiated on therapy after May 2020 were excluded from analysis, due to insufficient (less than 6 months) follow-up time. The remaining 183 patients were included in a retrospective cohort study comparing patients with ECOG 0, ECOG 1, and ECOG 2-4. Sex, age, type of cancer, and line of therapy were collected. Time on therapy was also calculated. Best response to therapy was determined (disease control or progressive disease). These baseline factors and outcomes were compared using ANOVA for numeric variables and chi-square tests of association for categorical variables. Time from initiation of ICI to death or hospice was also investigated and compared using a log-rank test. In addition, a multivariate Cox proportional hazards model was developed for the outcome, time to death/hospice, versus the predictors ECOG status, age, gender, and line of therapy. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated. Results: Of the 183 patients included in analysis, 31.7% had an ECOG of 0, 48.6% an ECOG of 1, and 19.7% an ECOG of 2-4. Non-small cell lung cancer and melanoma represented the majority of patients in each group. Gender and line of therapy did not differ between groups. There was a significant difference in age (p = 0.02) with mean age 62, 66, and 70 in ECOG 0,1, and 2-4, respectively. 54.6% of patients remained on therapy for at least 6 months (182 days), and there was no significant difference between groups in ability to complete 6 months of therapy (p = 0.32). For ECOG 0, 1, and 2-4, disease control was achieved in 67.2%, 59.6 %, and 41.7%, respectively (p = 0.048). Analysis of time to death/hospice with a log rank test and Kaplan Meier plot showed a significant difference between groups (p < 0.001). A multivariate Cox proportional hazards model revealed that patients with ECOG 0 had significantly longer time to death/hospice compared to patients in both other groups, after controlling for age, gender, and line of therapy (ECOG 1 vs. 0: HR 2.5, CI 1.27-4.9; ECOG 2-4 vs. 0: HR 2.83, CI 1.31-6.13). Conclusions: In this single institution retrospective study of patients receiving nivolumab or pembrolizumab for metastatic cancer, ECOG 0 was associated with disease control and increased time before death or transition to hospice.

Impact of genomic aberrations and additional therapies on survival outcomes of patients with operable non-small cell lung cancer (NSCLC) from the NEOSTAR study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8542-8542
Author(s):  
Nicolas Zhou ◽  
Boris Sepesi ◽  
Cheuk Hong Leung ◽  
Heather Y. Lin ◽  
William Nassib William ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Median Time ◽  
Proportional Hazards Model ◽  
Primary Lung Cancer ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Egfr Mutations ◽  
Genomic Aberration ◽  
Curative Intent ◽  
Genomic Aberrations

8542 Background: The NEOSTAR study compared nivolumab (N) vs. nivolumab plus ipilimumab (NI) with major pathological response (MPR; ≤10% viable tumor) as primary outcome. We report updated rates of treatment failure (TF), including in patients whose tumors harbored genomic aberrations, and outcomes of additional treatments. Methods: Patients (pts) with stage I-IIIA resectable NSCLC (AJCC 7th) were randomized to either neoadjuvant N or NI followed by surgery (n = 44). TF was defined as radiographic and/or biopsy-proven recurrence from primary lung cancer and/or death (treatment or cancer-related). Additional systemic therapy at recurrence included immuno-oncology (IO)-based therapy (IO or chemo-IO), targeted therapy (TT), or chemotherapy. Disease control rate (DCR) was defined as the proportion of pts with radiographic objective responses and stable disease at first restaging. Cox proportional hazards model was used to associate baseline characteristics and time to TF. Results: A total of 44 randomized pts were evaluated, the median follow-up was 35 months (mts) as of February 4, 2021. Among the 12 TF pts (12/44, 27%), 42% (5/12) did not undergo surgery on trial, 9 (9/44, 20%) experienced recurrence and 6 (6/44, 14%) died (1 non-cancer-related, 5 cancer-related). TF was less likely in smokers vs. never smokers (hazard ratio = 0.20, 95% confidence interval = 0.06-0.65, p = 0.007). Among pts with pathological specimen resected on trial, MPR was achieved in 40% (12/30) of non-TF pts. Only 1 (1/7, 14%) TF pt achieved MPR, but died of a non-cancer related cause. TF-free survival rate at 2 years was 92% in MPR and 78% in non-MPR pts. Eight (8/9, 89%) pts had tumors with canonical oncodriver aberrations (5 EGFR mutations, 1 with STK11+ KRAS Q61H mutations, 1 ALK translocation and 1 RET fusions). Of the 9 recurrences, 44% (4/9) were treated with IO therapy, and all 7 pts with targetable aberrations were treated with TT (3 after retreatment with IO therapies). Of the 4 pts retreated with IO therapy, duration between end of neoadjuvant and retreatment were 20, 17, 23, and 19 mts. Duration from retreatment until progression (PD) were 1, 1, and 2 mts, respectively. Last pt was treated without PD for 2 mts but switched to TT due to discovery of genomic aberration. IO retreatment achieved 25% DCR (1/4). In comparison, the DCR for TT treated pts was 71% (5/7, p = 0.242). Median time to treatment was 21 mts, and median time to PD was not reached. Among 32 non-TF pts, 12 had genomic analysis and 7 aberrations were found in 6 pts (2 STK11, 2 ERBB2, 1 STK11 + 1 KRAS G12C, and 1 KRAS G12C mutation). Conclusions: A 27% TF rate was observed after neoadjuvant IO. TF was less likely to occur in smokers and MPR pts, and 42% of TF pts did not undergo curative-intent surgery on trial. Genomic aberrations were common in pts with recurrence (89%), and treatment with TT achieved 71% DCR vs. 25% DCR with IO-based retreatment. Clinical trial information: NCT: 03158129.

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