scholarly journals Clinicopathologic correlates of pembrolizumab efficacy in patients with advanced NSCLC and a PD-L1 expression of ≥ 50%

2020 ◽  
Author(s):  
Alessio Cortellini ◽  
Marcello Tiseo ◽  
Giuseppe L Banna ◽  
Federico Cappuzzo ◽  
Joachim GJV Aerts ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Bone Metastases ◽  
Recursive Partitioning ◽  
Single Agent ◽  
Multivariable Analysis ◽  
Tobacco Exposure ◽  
Former Smokers ◽  
Never Smokers ◽  
Ecog Ps ◽  
Nsclc Patients

AbstractBackgroundSingle agent pembrolizumab represents the standard first line option for metastatic non-small-cell-lung-cancer (NSCLC) patients with a PD-L1 (programmed death-ligand 1) expression of ≥ 50%.MethodsWe conducted a multicenter study aimed at evaluating the clinicopathologic correlates of pembrolizumab efficacy in patients with treatment-naïve NSCLC and a PD-L1 TPS ≥ 50%.Results1026 consecutive patients were included. ECOG-PS ≥ 2 (p < 0.0001) and bone metastases (p = 0.0003) were confirmed to be independent predictors of a worse ORR. Former smokers (p = 0.0002), but not current smokers (p = 0.0532) were confirmed to have a significantly prolonged PFS compared to never smokers at multivariate analysis. ECOG-PS (p < 0.0001), bone metastases (p < 0.0001) and liver metastases (p < 0.0001) were also confirmed to be independent predictors of a worse PFS. Previous palliative RT was significantly related to a shortened OS (p = 0.0104), while previous non-palliative RT was significantly related to a prolonged OS (p = 0.0033). Former smokers (p = 0.0131), but not current smokers (p = 0.3433) were confirmed to have a significantly prolonged OS compared to never smokers. ECOG-PS (p < 0.0001), bone metastases (p < 0.0001) and liver metastases (p < 0.0001) were also confirmed to be independent predictors of a shortened OS. A PD-L1 expression of ≥ 90%, as assessed by recursive partitioning, was associated with significantly higher ORR (p = 0.0204), and longer and OS (p = 0.0346) at multivariable analysis.Conclusionspembrolizumab was effective in a large cohort of NSCLC patients treated outside of clinical trials. We confirmed that the absence of tobacco exposure, and the presence of bone and liver metastasis are associated with worse clinical outcomes to pembrolizumab. Increasing levels of PD-L1 expression may help identifying a subset of patients who derive a greater benefit from pembrolizumab monotherapy.

Evaluating the role of race in outcome of advanced non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitor (ICI): Our institutional experience.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9042-9042
Author(s):  
Bassel Nazha ◽  
Zhengjia Chen ◽  
Subir Goyal ◽  
Anne Engelhart ◽  
Jennifer Wilkinson Carlisle ◽  
...  
Keyword(s):  
Real World ◽  
Advanced Nsclc ◽  
Single Agent ◽  
Progression Free Survival ◽  
Minority Population ◽  
Duration Of Response ◽  
Diverse Patient Population ◽  
Institutional Experience ◽  
Ecog Ps ◽  
Nsclc Patients

9042 Background: Race-based differences in ICI efficacy for advanced NSCLC have not been studied due to under-representation of patients of minority background in pivotal trials. We systematically explored real-world differences in outcome in our diverse patient population. Methods: This is a retrospective review of clinical outcome of patients with advanced NSCLC treated with single-agent ICI between 2013 and July 2018 at the Winship Cancer Institute of Emory University. We performed univariate and multivariate analyses for overall survival (OS) and progression free survival (PFS) patients according to self-reported race and of OS according to gender and PD-L1 expression levels. Results: We analyzed clinical data from 90 eligible patients: Median age of 68.5 yrs, 51% male, White (W)/Black(B)/Asians(A) made up 62.3%/30.7%/5%; 36.5% had brain metastasis at the time of ICI initiation. The majority (85.9%) had ECOG PS ≤2; ICI was 1st line in 15 (16.9%), 2nd line in 59 (66.3%), 3rd line in 12 (13.5%) and nivolumab was the most commonly used agent (41.1%) followed by atezolizumab (32.2%) and pembrolizumab (26.7%). The median OS for the entire population was not reached (NR) (95%CI: 15.6, NR) while 12-month and 24-month OS rates were 63.8% (52.8%, 72.8%) and 53.1% (40.2%, 64.4%). The median OS, 12-month and 24-month OS rates for W and B respectively, were 23.6 months vs. NR; HR: 1.02 (95%CI: 0.51-2.04), p = 0.9571; 61.8% (47.7%, 73.2%) vs. 59.3% (38.6%, 75.0%) and 46.0% (27.9%, 62.4%) vs. 53.9% (32.8%, 70.9%). The overall response rate was 16.7%; 23.8% vs. 11% for B and W respectively. The median duration of response was comparable at 3.36 months vs. 2.94 months for W and B. The median PFS and 12-month PFS rate for W and B respectively were 5.5 (3.2, 14.8) vs. 3.0 (1.4, 10.7) months, p = 0.1350 and 40.0% (27.1%, 52.5%) vs. 29.6% (14.1%, 47.0%). Conclusions: Real-world analysis of our institutional experience showed no significant racial disparity in advanced NSCLC patients treated with ICI. Larger multi-institutional studies to include other US minority population would make our findings generalizable.

Bone metastases as predictors of treatment response and rapidly progressive disease in NSCLC patients on PD-1/PD-L1 immune checkpoint inhibitors (ICI).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20667-e20667
Author(s):  
Sally CM Lau ◽  
Lisa W Le ◽  
Elliot Charles Smith ◽  
Sze Wah Samuel Chan ◽  
Malcolm Ryan ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Bone Metastases ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Smoking Status ◽  
Clinicopathologic Characteristics ◽  
Metastatic Site ◽  
Overall Response ◽  
Nsclc Patients ◽  
Sites Of Metastases

e20667 Background: The tissue microenvironment associated with specific organ metastases potentially influences the efficacy of checkpoint inhibitors. The presence of liver metastases is a predictor of poor response and survival in melanoma and is correlated with reduced CD8+ T cell infiltration. Our study examined clinicopathologic characteristics, focusing on sites of metastatic disease, that are associated with poor outcomes. Methods: Advanced NSCLC patients treated with ≥1 cycle of ICI were reviewed. Baseline age, sex, histology, stage, smoking status, ethnicity, PD-L1 expression and sites of metastases were recorded. Best overall response (BOR) was determined by clinical imaging response and categorized ordinally as shrinkage, stable, or progression, adapted from RECIST for CR/PR, SD, PD. A rapidly progressive phenotype (RPP) was defined as BOR of progression and ICI use of ≤2 months. The association between sites of metastases and clinical outcomes were investigated using logistic and cox regression models. Results: Among 219 eligible patients, bone was the most common metastatic site (34.7%), followed by brain (21.5%), adrenals (14.2%), and liver (13.7%). Bone metastases (OR 0.45, p = 0.004) were associated with a worse BOR, while only a trend was observed for liver metastases (OR 0.47, p = 0.06). Adrenal metastases were associated with a better BOR (OR 2.08, p = 0.04). But thorax limited disease did not associate with BOR (OR 1.08, p = 0.76). In a multivariate model, bone was the only metastatic site associated with a worse BOR (OR 0.50, p = 0.01). Further, bone metastases were associated with RPP (adjusted OR 1.91, p = 0.04). Both bone (adjusted hazard ratio/aHR 1.61, p = 0.01) and liver metastases (aHR 1.80, p = 0.02) were associated with a shorter time-to-treatment-failure. The presence of liver (aHR 2.63, p < 0.001) but not bone (aHR 1.04, p = 0.86) metastases was a significant predictor of poor OS. Conclusions: We report a novel finding that the presence of bone metastases was associated with a worse clinical overall response on ICI and a rapidly progressive phenotype. Further investigations into the mechanisms of RPP in the presence of bone metastases are needed.

Specific organ metastases and survival of advanced non-small cell lung cancer (NSCLC) patients with EGFR mutation.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21527-e21527
Author(s):  
Tiantian Shi ◽  
Long Wang ◽  
Zhisong Fan ◽  
Li Feng ◽  
Jing Han ◽  
...  
Keyword(s):  
Lymph Node ◽  
Liver Metastases ◽  
Bone Metastases ◽  
Lymph Node Metastases ◽  
Egfr Mutation ◽  
Poor Response ◽  
The Poor ◽  
Node Metastases ◽  
Tki Treatment ◽  
Nsclc Patients

e21527 Background: The retrospective study was performed to evaluate the clinicopathological characteristics and survival associated with distant metastasis from advanced NSCLC with EGFR mutation. Methods: The records of metastasis NSCLC patients with EGFR mutation at the time of diagnosis between 2012 and 2018 were reviewed. The Kaplan-Meier method was used to assess survival curves and the log-rank test was used in the univariate analysis. The multivariate survival analysis were performed using the Cox proportional hazards model to investigate the effects of clinicopathological factors on survival. All the statistical analyses were performed using SPSS 23.0 statistical software and a statistically significant difference was determined as P < 0.05. Results: A total of 258 NSCLC patients with EGFR mutation were enrolled in this study, including 146 cases of female (56.6%), 241 cases of adenocarcinoma (93.4%) and 212 cases of non-smokers (82.2%). Among these patients, 65(25.2%), 111(43.0%), 22(8.5%), 107 (41.5%), 11(4.3%), 87 (33.7%), 65 (25.2%) had brain, bone, liver, lung, adrenal gland, pleural metastasis and extrathoracic lymph node metastases, respectively. The median OS of total patients was 32.9 months (95% CI: 29.8-36.0). In the univariate analysis, patients with metastases to the bone (p = 0.001), liver (p = 0.012), extrathoracic lymph node(p = 0.006), and pleural(p = 0.008) exhibited a poorer survival compared to those without metastases to these regions. Abdominal metastases (p = 0.005) and extremity metastases (p = 0.002) were statistically independent prognostic factors. Association between metastatic region and the response to TKI treatment, liver metastases (p = 0.033), extrathoracic lymph node metastases (p = 0.000) and bone metastases (p = 0.009) were correlated with the poor response of TKI treatment, and the abdominal metastasis ( p= 0.029) and extremity metastases ( p= 0.016) were correlated with the poor response of TKI treatment. Conclusions: Bone metastases, liver metastases, extrathoracic lymph node metastases and pleural metastases were independent prognostic factors of NSCLC patients with EGFR mutation. Liver metastases, extrathoracic lymph node metastases, and bone metastases were correlated with the poor response of TKI treatment.

Urine PGE-M to assess prostaglandin E2 (PGE2) levels in non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19026-e19026 ◽  
Author(s):  
L. Horn ◽  
G. Milne ◽  
A. Sandler ◽  
J. Morrow ◽  
D. Carbone ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Hepatic Function ◽  
Drug Intolerance ◽  
Previously Treated ◽  
Subsequent Phase ◽  
Former Smokers ◽  
Cox 2 ◽  
Pre Treatment ◽  
Never Smokers ◽  
Nsclc Patients

e19026 Background: COX-2 is often overexpressed in NSCLC leading to high systemic PGE2 levels that in turn play a role in NSCLC pathogenesis. Changes in urine PGE-M (the major PGE2 metabolite) reflect changes in systemic & intratumoral PGE2 [Csiki et al. Clin Cancer Res 11:6634, 2005]. A ≥70% decline in PGE-M in NSCLC patients (pts) treated with celecoxib (C) (400 mg bid) + docetaxel (D) was associated with an apparent survival benefit [Ibid]. To effect maximum COX-2 inhibition we tested a higher C dose in a subsequent phase II trial. Methods: Eligibility: previously treated NSCLC, PS 0–2, evaluable/measurable disease, adequate marrow, renal & hepatic function, no current NSAID or sulfa allergy. Urine PGE-M measured prior to & 5–10 days after C 600 mg PO bid. Pts with ≥70% decline in PGE-M continued on C + D 75 mg/m2 or pemetrexed 500 mg/m2 q3wk x 4 cycles followed by maintenance C 400 mg PO bid until PD or drug intolerance. Results: 21 pts enrolled; F=7, M=14; 2 ineligible (1 carcinoid; 1 elevated LFT); 2 stopped C early (1 ARF; 1 pruritus). Mean PGE-M levels decreased from 38.9 to 7.8 ng/mg Cr pre- & post-C (mean change = 80%; P=0.002). The mean decline was greater in current & former smokers (81%; P=0.002) compared to never smokers (46%; P=0.19). Males had higher pre- treatment PGE-M (44 vs. 28.8 ng/mg Cr; P=0.21). Males had a significant decrease in mean PGE-M levels after C (78%; P=0.011); a similar albeit not significant change occurred in females (P=0.12). 12 screened pts (57%) had a ≥70% decline in PGE-M & received treatment with C + chemotherapy; 8 pts are evaluable for response; SD = 6; PD = 2. Treatment was well tolerated with no cardiac toxicities noted. Conclusions: These preliminary data indicate C 600 mg bid effectively inhibits intratumoral COX-2 in >50% NSCLC pts, a higher percentage than our previous trial using C 400 mg bid. The effect is greatest in former & current smokers & males compared to never smokers & females. Toxicities are acceptable. Accrual is ongoing. [Funding: VICC Lung Cancer SPORE CA90949]. No significant financial relationships to disclose.

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]

Gefitinib plus celecoxib in chemotherapy-naïve patients with stage IIIB/IV non-small cell lung cancer (NSCLC): A phase II study from the Hoosier Oncology Group

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7066-7066 ◽  
Author(s):  
A. K. Agarwala ◽  
L. Einhorn ◽  
W. Fisher ◽  
D. Bruetman ◽  
J. McClean ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Day Treatment ◽  
Single Agent ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Stage Iiib ◽  
Never Smokers ◽  
Ecog Ps

7066 Background: Gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR) pathway, has single agent activity in NSCLC. Preclinical studies demonstrate significant interactions between the EGFR and cyclo-oxygenase 2 (COX-2) pathways and that simultaneous inhibition against NSCLC may have benefits over gefitinib alone. Methods: Eligibility required that pts were chemotherapy-naïve, had stage IIIb (with pleural effusion) or IV NSCLC and an ECOG PS 0–1. Pts received gefitinib 250mg orally daily plus celecoxib 400mg orally every 12 hours. Cycles consisted of 21 day treatment and continued until unacceptable toxicity or progression of disease. The primary objective of this single arm, two-stage, phase II study was to evaluate the overall response rate. If ≤ 10 out of 30 pts achieved a complete (CR) or partial response (PR), the study would be stopped early. If >10 out of 30 pts had a CR or PR, enrollment would continue to 50 pts. Results: From 1/04 to 11/04, 31 pts were enrolled: male/female 13/18; median age 70.8 years (range, 19–93); 67.7% had adenocarcinoma; ECOG PS 0/1 13/18; stage IIIb/IV 2/29; 5 were current smokers, 9 were remote (>30 years) or never smokers, 16 quit smoking > 3 months ago. Median number of cycles was 4 (range, 0–16). 6 pts (19.4%) discontinued therapy due to toxicity, including 3 who died due to treatment. Select grade 3/4 toxicities included: pulmonary (6.5%), hepatic (6.5%), diarrhea (6.5%), skin (3.2%). Responses included PR 5 (16.1%), stable disease 8 (25.8%), and progressive disease 18 (58.1%). Median duration of response, progression free survival, and overall survival was 5.7, 2.8, and 7.2 months, respectively. All responders were females with adenocarcinoma, 2 were remote or never smokers and 3 were former smokers. Conclusion: Gefitinib plus celecoxib in an unselected population of chemotherapy naïve patients with advanced NSCLC and a PS of 0–1 has a lower response rate and overall efficacy compared with historical controls of chemotherapy. [Table: see text]

Efficacy of immune checkpoint blockade alone or combined with chemotherapy and smoking status in NSCLC: A systematic review and meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21661-e21661
Author(s):  
Shanshan Wang ◽  
You-En Lin ◽  
Dan Yang ◽  
Guoqiang Wang ◽  
Shangli Cai ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Standard Treatment ◽  
Smoking Status ◽  
Meta Analysis ◽  
Single Agent ◽  
Synergetic Effect ◽  
Tobacco Consumption ◽  
Immune Checkpoint Blockade ◽  
Never Smokers ◽  
Nsclc Patients

e21661 Background: Tobacco smoking is a critical cause of mutational burden and immuno-microenvironmental alteration in non-small cell lung cancer (NSCLC). However, the association between tobacco consumption and the synergetic effect of chemotherapy on single-agent immunotherapy remains controversial. Methods: We systematically searched PubMed, the Cochrane Central library and Embase, for the RCTs of ICI in NSCLC with HR for both PFS and OS according to smoking status. Random-effects model were used to pool estimates of survival HR and 95%CI. Subgroup analysis and meta-regression were implemented to investigate the source of heterogeneity. Results: In total, 13 eligible RCTs of 8154 NSCLC patients (6800 ever-smokers and 1354 never-smokers) were included. PFS benefit from immunotherapy comparing standard treatment remarkably differed between ever-smokers and never-smokers (P = 0.005), where significant PFS benefit was observed in ever-smokers (pooled HR = 0.72, 95%CI 0.63-0.81, P < 0.001) instead of never-smokers (pooled HR = 0.98, 95%CI 0.73-1.31, P = 0.90). In never-smokers, the choice of regimen (monotherapy vs. combination therapy) considerably impacted the benefit of PFS (HR = 2.21, 95%CI 1.35-3.61, P = 0.005) and OS (HR = 1.99, 95%CI 1.03-3.82, P = 0.041). Compared to standard treatment, monotherapy worsened PFS (HR = 1.39, 95%CI 1.01-1.90, P = 0.046) and did not improve OS (HR = 0.91, 95%CI 0.72-1.14) in never-smokers, while combination therapy dramatically delayed both progression (HR = 0.63, 95%CI 0.49-0.81, P < 0.001) and death (HR = 0.45, 95%CI 0.25-0.82, P = 0.010). Conclusions: Tobacco smoke was associated with larger PFS, but not OS benefit from immunotherapy. In never-smokers, not ever-smokers, combination with chemotherapy compared to single-agent ICI might confer significantly greater delays of both progression and death. [Table: see text]

scholarly journals Abnormal sympathetic nerve activity in women exposed to cigarette smoke: a potential mechanism to explain increased cardiac risk

2013 ◽  
Vol 305 (10) ◽  
pp. H1560-H1567 ◽  
Author(s):  
Holly R. Middlekauff ◽  
Jeanie Park ◽  
Harsh Agrawal ◽  
Jeffrey A. Gornbein
Keyword(s):  
Blood Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Cold Pressor Test ◽  
Tobacco Exposure ◽  
Menstrual Phase ◽  
Nerve Activity ◽  
Baroreflex Control ◽  
Former Smokers ◽  
Never Smokers

In women, cardiac deaths attributable to tobacco exposure have reached the same high levels as men. Normally, sympathetic nerve activity (SNA) fluctuates according to the menstrual phase, but in habitual smokers, SNA levels remain constant. Our purpose is to extend these observations to other groups of women exposed to tobacco smoke and to explore potential mechanisms. We hypothesize that women exposed to secondhand smoke, but not former smokers, have nonfluctuating SNA compared with never smokers, and that impaired baroreflex suppression of SNA, and/or heightened central SNA responses, underlie this nonfluctuating SNA. We also hypothesize that female smokers have impaired nocturnal blood pressure dipping, normally mediated by modulation of SNA. In 49 females (19 never, 12 current, 9 former, 9 passive smokers), SNA was recorded (microneurography) during high- and low-hormone ovarian phases at rest, during pharmacological baroreflex testing, and during the cold pressor test (CPT). Twenty-four hour blood pressure (BP) monitoring was performed. Current and passive smokers, but not former smokers, had a nonfluctuating pattern of SNA, unlike never smokers in whom SNA varied with the menstrual phase. Baroreflex control of SNA was significantly blunted in current smokers, independent of menstrual phase. In passive smokers, SNA response to CPT was markedly increased. Nondipping was unexpectedly high in all groups. SNA does not vary during the menstrual cycle in active and passive smokers, unlike never and former smokers. Baroreflex control of SNA is blunted in current smokers, whereas SNA response to CPT is heightened in passive smokers. Smoking cessation is associated with return of the altered SNA pattern to normal.

Response to single-agent (SA) chemotherapy (CTx) after immunotherapy exposure in non-small cell lung cancer (NSCLC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9083-9083 ◽  
Author(s):  
Gustavo Schvartsman ◽  
S. Andrew Peng ◽  
Giorgios Bis ◽  
J. Jack Lee ◽  
Marcelo Felipe Kuperman Benveniste ◽  
...  
Keyword(s):  
Univariate Analysis ◽  
Single Agent ◽  
Progression Free Survival ◽  
Eligibility Criteria ◽  
Free Survival ◽  
Programmed Death ◽  
Never Smokers ◽  
Md Anderson ◽  
Nsclc Patients ◽  
Tumor Types

9083 Background: Overall response rates (ORR) to 2nd-line SACTx in NSCLC have consistently not exceeded 15%. Exploratory analysis of clinical trials in various tumor types have demonstrated potential improvements in ORR to CTx after exposure to vaccine-based immunotherapy. The objective of this retrospective study was to determine if SACTx (3rd-line or beyond) would yield improved ORR when given after exposure to programmed-death-(ligand)1 inhibitors (PD1i) in metastatic NSCLC. Methods: Eligibility criteria - patients registered in the Thoracic GEMINI database of MD Anderson treated between 06/12 and 11/16 who received at least one SACTx as 3rd-line or beyond, following progression after platinum-based CTx and PD1i. We computed efficacy outcomes to each therapy, including ORR by RECIST v1.1, progression-free survival (PFS) and overall survival (OS). Results: Of 306 PD1i-treated patients registered in the database, 28 met eligibility criteria - 54% were male, median age 66 years, 82% adenocarcinoma, 29% never smokers. The PD1i and SACTx most commonly used were nivolumab (82%) and docetaxel (54%). ORR to SACTx after exposure to PD1i was 39% (11/28 patients, 8 confirmed). In contrast, ORR to 1st-line CTx in this cohort was 30% (Table). Liver metastasis and pembrolizumab as the PD1i of choice were the only factors associated with response to SACTx on univariate analysis (p < 0.05). Conclusions: In NSCLC patients, ORR to SACTx after immunotherapy exposure was higher compared to historical data from the pre-PD1i era, and approached ORR to 1st-line platinum-based CTx. Further investigation of a possible chemosensitization effect by immunotherapy is warranted. [Table: see text]

Cabozantinib (CABO) plus durvalumab (DURVA) in patients with advanced and chemotherapy-treated bladder carcinoma of urothelial and non-urothelial histology: An open-label, single-arm, phase 2 trial.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. TPS536-TPS536 ◽  
Author(s):  
Andrea Necchi ◽  
Patrizia Giannatempo ◽  
Daniele Raggi ◽  
Andrea Anichini ◽  
Giuseppina Calareso ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Immune Cell ◽  
Single Agent ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Effective Combination ◽  
Platinum Based Chemotherapy ◽  
Ecog Ps

TPS536 Background: DURVA and CABO have shown single-agent activity in patients (pts) with urothelial carcinoma (UC). Their combination may result in prolonging overall survival (OS) in pts who have failed prior platinum-based chemotherapy (CT). Additionally, DURVA+CABO may be an effective combination for treating subgroup of pts like those with bone metastases only (not having RECIST-measurable disease) or with non-UC histology. Methods: In an open-label, single-arm, multicenter, phase 2 trial, pts will assume CABO 40 mg daily, orally, and will be administered DURVA 1500 mg, intravenously, q28 days, until disease progression (PD, RECIST 1.1) or onset of unacceptable toxicity. Treatment beyond PD is not allowed. Key inclusion criteria: ECOG-PS 0-1, bladder or upper tract primary tumor, UC and non-UC histology, failure of 1 or 2 platinum-based CT for metastatic disease (2nd-to-3rd line only). Neoadjuvant/adjuvant CT is counted if relapse occurred ≤6 months (m) of the last CT cycle. Response is evaluated by RECIST criteria v.1.1 q2 cycles. The primary endpoint of the study is OS. The target is to detect an improvement in median OS from ≤6m (H0) to ≥9m(H1). To achieve 90% power with a one-sided non-parametric test at 5% significance, 122 pts must will be accrued over 36m and follow-up may be closed 12m after the end of accrual. PD-L1 expression will be assessed using with the Ventana SP142 assay, and categorized as high (≥25% of tumor cells [TC] or immune cells [IC]) or low/negative ( < 25% TC or IC). The decision on whether or not to undertake PD-L1+ cohort expansion will be based on predictive power (PP) calculation: a PP ≥30% will be regarded as promising and necessary to continue. An interim analysis is planned after 24m (50% expected events). This analysis will be based on PP. The criterion for stopping the trial because of futility will be a PP < 20%. Analyses on tissue/blood samples will include immune-cell profiling, cytokine assessment, gene expression analyses and next-generation sequencing (FoundationOne). FDG-PET response in bone metastases will represent another translational endpoint (EudraCT number 2017-000580-32). Clinical trial information: 2017-000580-32.

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