Impact of cachexia in advanced NSCLC patients treated with PD-1 inhibitor.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 44-44
Author(s):  
Hitomi Jo ◽  
Hidehito Horinouchi ◽  
Shigehiro Yagishita ◽  
Yuki Shinno ◽  
Yusuke Okuma ◽  
...  
Keyword(s):  
Body Weight ◽  
Confidence Interval ◽  
Advanced Nsclc ◽  
Smoking Status ◽  
Hazard Ratio ◽  
Disease Stage ◽  
Cancer Center ◽  
Study Cohort ◽  
Durable Response ◽  
Nsclc Patients

44 Background: Cancer cachexia is known to a multifactorial catabolic syndrome and is observed 15-40% in general cancer population with worse prognosis. A recent study suggested a shorter survival period in non-small cell lung cancer (NSCLC) patients with a higher pembrolizumab clearance associated with cachexia. We here conducted analyses for the clinical impact of cachexia in advanced NSCLC treated with pembrolizumab. Methods: We evaluated consecutive advanced NSCLC patients who received pembrolizumab between March 2017 and December 2018 at the National Cancer Center Hospital. Cachexia was defined as a body weight loss >5% over the past 6 months or >2% in patients with a BMI <20 kg/m2 at the start of treatment. Information on patient age, sex, performance status, histology, driver mutation status, smoking status, disease stage, treatment line, and PD-L1 tumor proportion score were recorded. The overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were investigated according to the presence of cachexia. Univariate and multivariate analyses were performed. Results: A total of 157 NSCLC patients received pembrolizumab during the study period. Of these, 134 patients with information for body weight were included in the final analysis. Patients with cachexia accounted for 35% (47 out of 134) of this cohort. The ORR was 38% among the patients with cachexia and 35% among those without cachexia. The median PFS was significantly shorter for the patients with cachexia than for the patients without cachexia (median PFS, 4.2 months vs. 7.1 months; hazard ratio, 1.63; 95% confidence interval, 1.06 – 2.53; P = 0.02). The median OS was significantly shorter for the patients with cachexia (median OS, 8.6 months vs. NR; hazard ratio, 1.83; 95% confidence interval, 1.03-3.25; P = 0.04). The presence of cachexia was independently associated with a shorter PFS in a multivariate analysis. Conclusions: The presence of cachexia was significantly associated with a shorter PFS and OS in our study cohort. Screening for cachexia may help to identify patients who are more likely to achieve a durable response.

Experience of weight loss and its burden in patients with non-small cell lung cancer: Results of an online survey.

2016 ◽  
Vol 34 (26_suppl) ◽  
pp. 71-71 ◽  
Author(s):  
Ana Maria Rodriguez ◽  
Elizabeth M Duus ◽  
John Friend
Keyword(s):  
Quality Of Life ◽  
Lung Cancer ◽  
Weight Loss ◽  
Body Weight ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Appetite Loss ◽  
Nsclc Patients

71 Background: The main objectives of this study were to characterize and compare the burden of non-small cell lung cancer (NSCLC) patients who reported considerable weight loss ( ≥ 5% of their body weight in the past 6 months or ≥ 2% for a BMI less than 20 kg/m2) to those who did not. Methods: 95 advanced NSCLC patients were surveyed from the online patient-powered community PatientsLikeMe. Self-reported demographic and clinical characteristics were recorded. Appetite, distress and concerns, health-related quality of life (QLQ-C15-PAL) and anorexia-cachexia symptoms/concerns (FAACT A/CS) were summarized. The results obtained between patients who lost considerable weight and those who did not were compared, using a two-tailed t-test or a Kruskal-Wallis test. Patients with weight loss were additionally asked open-ended questions on burden and concerns. Results: 35 (37%) patients were classified as having considerable weight loss at the time of the survey and 60 (63%) where classified without. Most patients were female (81%), American (81%), and mean age was 59 years. 61% of patients indicated not receiving either chemotherapy or radiotherapy at the time of the survey. Patients with weight loss reported significantly (p < 0.05) lower overall quality of life (55.2 vs. 66.9), worsened anorexia-cachexia symptoms/concerns (30.7 vs. 36.0), and higher symptomology, specifically fatigue (64.8 vs. 49.1), nausea (19.5 vs. 9.2), and appetite loss (41.0 vs. 23.9) – than patients without weight loss. In addition, significantly more patients who lost weight reported moderate/high distress levels than patients who did not (71% vs. 38%). For patients with weight loss, change in food taste, fatigue, and decrease in appetite were the most frequently reported symptoms with the greatest impact on their lives. Conclusions: Our results support that weight loss negatively affects cancer patients’ quality of life and is associated with more distress and symptoms—particularly fatigue, and appetite loss. Weight loss-related symptoms also significantly impact their lives. Interventions targeted at maintaining/increasing body weight may help to improve well-being and reduce key symptoms in advanced NSCLC patients with considerable weight loss.

Body weight response with anamorelin in advanced non-small cell lung cancer (NSCLC) patients with anorexia/cachexia: Pooled analysis of two phase III trials.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10097-10097 ◽  
Author(s):  
David Christopher Currow ◽  
Jennifer S. Temel ◽  
Amy Pickar Abernethy ◽  
John Friend ◽  
Ruben Giorgino
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Advanced Nsclc ◽  
Pooled Analysis ◽  
Phase Iii ◽  
P Value ◽  
Double Blind ◽  
Entire Study ◽  
Ghrelin Receptor ◽  
Nsclc Patients

10097 Background: Anorexia/cachexia commonly occurs in patients with advanced NSCLC and is associated with increased morbidity and mortality. In two randomized, double-blind, placebo-controlled phase 3 trials in NSCLC patients with cachexia, the ghrelin receptor agonist anamorelin was well tolerated and significantly increased body weight, lean and fat mass, and anorexia/cachexia symptom burden over 12 weeks compared to placebo (Temel J. Lancet Oncol. 2016). Since an involuntary weight loss of ≥ 5% is an established diagnostic criterion for cancer anorexia/cachexia, an analysis was conducted to assess the proportion of patients with ≥ 5% increase in body weight. Methods: NSCLC patients [ROMANA 1 (NCT01387269; N = 484) and ROMANA 2 (NCT01387282; N = 495)] with stage III/IV disease and cachexia (BMI < 20 kg/m2 or ≥ 5% weight loss during prior 6 months) were randomized 2:1 to receive 100 mg once daily oral anamorelin or placebo up to 12 weeks. A pooled analysis was conducted post-hoc in the modified intent-to-treat population (N = 829) to measure the proportion of patients with ≥ 5% increase in body weight at the end of study (or last observation carried forward since week 6 or 9). Results: The percentage of patients with ≥ 5% increase in body weight at the end of study was significantly higher in the anamorelin arm (N = 188/552, 34.1%) compared to placebo (N = 37/277; 13.4%). Among patients with BMI < 20kg/m2 at baseline (N = 182), 47.3% (N = 53/112) of anamorelin patients had a weight increase of ≥ 5% compared to 17.4% (N = 12/69) in the placebo arm. In both cases the nominal p-value was lower than 0.0001. Conclusions: Data from two published large pivotal studies in advanced NSCLC patients with anorexia/cachexia suggest that anamorelin treatment effect size on body weight is clinically relevant, as shown by the higher response rate achieved when the stringent cut-off of ≥ 5% weight gain was applied. The proportion of patients with BMI < 20kg/m2 that benefited from anamorelin treatment was greater than the proportion of patients who benefited in the entire study sample, suggesting that patients with more advanced cachexia may still benefit from anamorelin treatment. Clinical trial information: ROMANA 1: NCT01387269; ROMANA 2: NCT01387282.

scholarly journals Silibinin Suppresses Tumor Cell-Intrinsic Resistance to Nintedanib and Enhances Its Clinical Activity in Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4168
Author(s):  
Joaquim Bosch-Barrera ◽  
Sara Verdura ◽  
José Carlos Ruffinelli ◽  
Enric Carcereny ◽  
Elia Sais ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Advanced Nsclc ◽  
Hazard Ratio ◽  
Pharmacological Intervention ◽  
Study Cohort ◽  
Intrinsic Resistance ◽  
Platinum Based Chemotherapy ◽  
Synergistic Cytotoxicity

The anti-angiogenic agent nintedanib has been shown to prolong overall and progression-free survival in patients with advanced non-small-cell lung cancer (NSCLC) who progress after first-line platinum-based chemotherapy and second-line immunotherapy. Here, we explored the molecular basis and the clinical benefit of incorporating the STAT3 inhibitor silibinin—a flavonolignan extracted from milk thistle—into nintedanib-based schedules in advanced NSCLC. First, we assessed the nature of the tumoricidal interaction between nintedanib and silibinin and the underlying relevance of STAT3 activation in a panel of human NSCLC cell lines. NSCLC cells with poorer cytotoxic responses to nintedanib exhibited a persistent, nintedanib-unresponsive activated STAT3 state, and deactivation by co-treatment with silibinin promoted synergistic cytotoxicity. Second, we tested whether silibinin could impact the lysosomal sequestration of nintedanib, a lung cancer cell-intrinsic mechanism of nintedanib resistance. Silibinin partially, but significantly, reduced the massive lysosomal entrapment of nintedanib occurring in nintedanib-refractory NSCLC cells, augmenting the ability of nintedanib to reach its intracellular targets. Third, we conducted a retrospective, observational multicenter study to determine the efficacy of incorporating an oral nutraceutical product containing silibinin in patients with NSCLC receiving a nintedanib/docetaxel combination in second- and further-line settings (n = 59). Overall response rate, defined as the combined rates of complete and partial responses, was significantly higher in the study cohort receiving silibinin supplementation (55%) than in the control cohort (22%, p = 0.011). Silibinin therapy was associated with a significantly longer time to treatment failure in multivariate analysis (hazard ratio 0.43, p = 0.013), despite the lack of overall survival benefit (hazard ratio 0.63, p = 0.190). Molecular mechanisms dictating the cancer cell-intrinsic responsiveness to nintedanib, such as STAT3 activation and lysosomal trapping, are amenable to pharmacological intervention with silibinin. A prospective, powered clinical trial is warranted to confirm the clinical relevance of these findings in patients with advanced NSCLC.

scholarly journals Immune-Related Adverse Events Are Associated With Clinical Benefit in Patients With Non-Small-Cell Lung Cancer Treated With Immunotherapy Plus Chemotherapy: A Retrospective Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Kenji Morimoto ◽  
Tadaaki Yamada ◽  
Chieko Takumi ◽  
Yuri Ogura ◽  
Takayuki Takeda ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Confidence Interval ◽  
Small Cell Lung Cancer ◽  
Clinical Outcomes ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Hazard Ratio ◽  
Small Cell Lung

BackgroundThe immunotherapy plus chemotherapy combination is one of the most promising treatments in advanced non-small-cell lung cancer (NSCLC). Immunotherapy often causes immune-related adverse events (irAEs), which have been reported to be associated with the good clinical outcomes. However, the effects of immunotherapy plus chemotherapy remain unknown. In this study, we investigated the association between irAEs caused by immunotherapy plus chemotherapy and clinical efficacy in patients with advanced NSCLC.Materials and MethodsWe retrospectively analyzed the data of patients with advanced NSCLC, who received a combination of immunotherapy plus chemotherapy at six institutions in Japan between January 2019 and September 2019. We examined the effect of irAEs on various clinical outcomes.ResultsWe included 70 patients with advanced NSCLC. Patients were divided into two groups: patients with irAEs and patients without irAEs. Patients with irAEs had significantly longer progression-free survival than those without irAEs on univariate (hazard ratio 0.53, 95% confidence interval 0.30–0.93, p = 0.026) and multivariate (hazard ratio 0.53, 95% confidence interval 0.29–0.97, p = 0.041) analyses. In addition, patients with grade 1–2 irAEs (mild irAEs) had significantly longer progression-free and overall survival than those with grade 3-5 irAEs (severe irAEs) or without irAEs on univariate (398 days versus 189 days, respectively; p = 0.0061) and multivariate (not reached versus 412 days, respectively; p = 0.021) analyses.ConclusionPatients with NSCLC who experienced mild irAEs showed better response to treatment with immunotherapy plus chemotherapy than those with severe irAEs or without irAEs. Further large-scale research is warranted to confirm these findings.

Postoperative adjuvant chemotherapy for thoracic pathological T3N0M0 esophageal cancer: A propensity score-matched analysis (APEC Study 1).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15537-e15537
Author(s):  
Qifeng Wang ◽  
Tao Li ◽  
Yongtao Han ◽  
Qiang Li ◽  
Lin Peng ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Propensity Score ◽  
Confidence Interval ◽  
Hazard Ratio ◽  
Postoperative Chemotherapy ◽  
Phase Iii ◽  
R0 Resection ◽  
Study Cohort ◽  
Postoperative Adjuvant Chemotherapy ◽  
Matched Samples

e15537 Background: The role of postoperative chemotherapy (POCT) in thoracic esophageal squamous cell carcinoma (TESCC) has not been addressed . The aim of this study was to investigate whether POCT after an R0 resection improves outcomes in pT3N0M0 TESCC compared with operation alone. Methods: This study included 604 patients with pT3N0M0 TESCC who were treated at Sichuan Cancer Hospital from January 2009 to December 2017. The patients were divided into two groups: a surgery plus postoperative chemotherapy group (PORT group) comprising Surgery alone patients who underwent after an R0 resection and a surgery group (S group). Propensity score matching was used to create patient groups that were balanced across several covariates (n= 246 in each group). Outcome measures included overall survival (OS), disease free survival (DFS). Results: In the whole group 5-year OS and PFS were 58.4% and 56.0%. In the overall study cohort, 5-year OS (68.3% versus 50.4%, p < 0.0001) and DFS (65.5% versus 45.8%, p < 0.0001) rates were significantly higher in the POCT group than in the S group. These data were confirmed in the matched samples (5-year OS, 68.3% versus 49.5% [p < 0.0001]; DFS, 65.5% versus 42.5% [p < 0.0001]). Multivariate Cox analyses in the matched samples revealed that surgery and postoperative POCT were independently associated with longer OS (hazard ratio = 0.553, 95% confidence interval: 0.391–0.726, p < 0.0001) and longer DFS (hazard ratio = 0.556, 95% confidence interval: 0.416–0.744, p < 0.0001) than resection alone. Subgroup analysis found : POCT with IIA in pT3N0M0 have not longer OS and DFS ( p = 0.122 and p = 0.193). POCT with IIB in pT3N0M0 have the longer OS and DFS(p < 0.0001 both). Conclusions: Postoperative adjuvant Chemotherapy is strongly associated with improved OS and DFS in patients with pT3N0M0 TESCC. A multicenter, randomized phase III clinical trial is warranted to confirm these findings.

scholarly journals Severe weight loss after minimally invasive oesophagectomy is associated with poor survival in patients with oesophageal cancer at 5 years

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yasufumi Koterazawa ◽  
Taro Oshikiri ◽  
Gosuke Takiguchi ◽  
Naoki Urakawa ◽  
Hiroshi Hasegawa ◽  
...  
Keyword(s):  
Weight Loss ◽  
Enteral Nutrition ◽  
Confidence Interval ◽  
Minimally Invasive ◽  
Hazard Ratio ◽  
University Hospital ◽  
Cancer Center ◽  
Jejunostomy Tube ◽  
Severe Weight Loss ◽  
Minimally Invasive Oesophagectomy

Abstract Background Patients often experience severe weight loss after oesophagectomy. Enteral nutrition via a feeding jejunostomy tube (FT) is commonly practised. This study aimed to assess the effect of severe weight loss postoperatively and enteral nutrition via an FT on long-term prognosis after oesophagectomy. Methods This study analysed 317 patients who underwent minimally invasive oesophagectomy at Kobe University Hospital and Hyogo Cancer Center from 2010 to 2015. The patients’ body weight was evaluated at 3 months postoperatively. They were organised into the severe weight loss (n = 65) and moderate weight loss (n = 252) groups. Furthermore, they were categorised into the FT group (184 patients who had an FT placed during oesophagectomy) and no-FT group (133 patients without FT). Patients (119 per group) matched for the FT and no-FT groups were identified via propensity score matching. Results The 5-year overall survival (OS) rate in the severe weight loss group was significantly lower (p = 0.024). In the multivariate analysis, tumour invasion depth (pT3-4), preoperative therapy and severe weight loss had a worse OS (hazard ratio = 1.89; 95% confidence interval = 1.12–3.17, hazard ratio = 2.11; 95% confidence interval = 1.25–3.54, hazard ratio = 1.82; 95% confidence interval = 1.02–3.524, respectively). No significant differences in the number of severe weight loss patients and OS were found between the FT and no-FT groups. Conclusion Severe weight loss is significantly associated with poor OS. In addition, enteral nutrition via an FT did not improve the severe weight loss and OS.

scholarly journals Smoking Status at Diagnosis and Colorectal Cancer Prognosis According to Tumor Lymphocytic Reaction

2020 ◽  
Vol 4 (5) ◽  
Author(s):  
Kenji Fujiyoshi ◽  
Yang Chen ◽  
Koichiro Haruki ◽  
Tomotaka Ugai ◽  
Junko Kishikawa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Confidence Interval ◽  
Cancer Patients ◽  
Cpg Island ◽  
Smoking Status ◽  
Disease Stage ◽  
Health Study ◽  
Cancer Tissue ◽  
Colon And Rectal Cancer ◽  
Prognostic Association

Abstract Background Smoking has been associated with worse colorectal cancer patient survival and may potentially suppress the immune response in the tumor microenvironment. We hypothesized that the prognostic association of smoking behavior at colorectal cancer diagnosis might differ by lymphocytic reaction patterns in cancer tissue. Methods Using 1474 colon and rectal cancer patients within 2 large prospective cohort studies (Nurses’ Health Study and Health Professionals Follow-up Study), we characterized 4 patterns of histopathologic lymphocytic reaction, including tumor-infiltrating lymphocytes (TILs), intratumoral periglandular reaction, peritumoral lymphocytic reaction, and Crohn’s-like lymphoid reaction. Using covariate data of 4420 incident colorectal cancer patients in total, an inverse probability weighted multivariable Cox proportional hazards regression model was conducted to adjust for selection bias due to tissue availability and potential confounders, including tumor differentiation, disease stage, microsatellite instability status, CpG island methylator phenotype, long interspersed nucleotide element-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Results The prognostic association of smoking status at diagnosis differed by TIL status. Compared with never smokers, the multivariable-adjusted colorectal cancer–specific mortality hazard ratio for current smokers was 1.50 (95% confidence interval = 1.10 to 2.06) in tumors with negative or low TIL and 0.43 (95% confidence interval = 0.16 to 1.12) in tumors with intermediate or high TIL (2-sided Pinteraction = .009). No statistically significant interactions were observed in the other patterns of lymphocytic reaction. Conclusions The association of smoking status at diagnosis with colorectal cancer mortality may be stronger for carcinomas with negative or low TIL, suggesting a potential interplay of smoking and lymphocytic reaction in the colorectal cancer microenvironment.

scholarly journals LMD-06. A NSCLC patient with leptomeningeal metastasis harboring rare EGFR mutations G719S and L861Q benefited from doubling dosage of osimertinib: a case report

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii8-iii8
Author(s):  
Hui Wang ◽  
Changguo Shan ◽  
Weiping Hong ◽  
Lei Wen ◽  
Mingyao Lai ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Kinase Inhibitor ◽  
Nsclc Patient ◽  
Growth Factor Receptor ◽  
Leptomeningeal Metastasis ◽  
Egfr Mutations ◽  
Optimal Dosage ◽  
Durable Response ◽  
Disturbance Of Consciousness ◽  
Nsclc Patients

Abstract Leptomeningeal metastasis (LM) is a rare but lethal complication of advanced non-small cell lung cancer (NSCLC) that has a devastating impact on patient survival and quality of life. Osimertinib, an irreversible tyrosine kinase inhibitor, is approved as a therapy for advanced NSCLC with epidermal growth factor receptor (EGFR) mutation. However, the efficacy and optimal dosage of osimertinib in the treatment of NSCLC patients with LM who harbor uncommon EGFR mutations have yet to be fully investigated. Herein, we report a case of an advanced NSCLC patient with LM carrying EGFR G719S and L861Q, who was successfully treated by osimertinib at 160 mg. The patient initially presented with clear cell renal carcinoma and renal metastatic adenocarcinoma, and underwent right nephrectomy. At 2 months after nephrectomy, He developed a disturbance of consciousness and was subsequently diagnosed with NSCLC with LM by meningeal biopsy pathology and cerebrospinal fluid (CSF) cytology. Next-generation sequencing detected the rare EGFR mutations G719S and L861R in the meningeal biopsy tissues. The patient was then administered osimertinib at 80 mg quaque die (QD); after 1 month of treatment, his symptoms were alleviated. However, two months later, he experienced epileptic episode. Subsequently, the osimertinib dosage was doubled to 160 mg QD. After 1 month of treatment, the patient achieved central nervous system (CNS) response, and at the time of this manuscript’s submission, he had maintained stable disease (SD) for more than 1 year. To our knowledge, this study provides the first clinical evidence that the administration of osimertinib at 160 mg once daily can achieve an encouraging, durable response in an NSCLC patients with LM carrying EGFR G719S and L861Q. Aslo, it is recommended to consider performing leptomeningeal biopsy for precision treatment in NSCLC paiernts with leptomeningeal metastasis.

Results from a phase I safety lead-in study investigating the combination of erlotinib and the histone deacetylase inhibitor entinostat in patients with advanced NSCLC

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14545-e14545 ◽  
Author(s):  
K. Konduri ◽  
A. I. Spira ◽  
R. M. Jotte ◽  
T. Boyd ◽  
T. Boyd ◽  
...  
Keyword(s):  
Cell Lines ◽  
Kinase Inhibitors ◽  
Advanced Nsclc ◽  
Smoking Status ◽  
Nsclc Cell ◽  
10Mg Dose ◽  
Pharmacokinetic Analysis ◽  
Phase 2 ◽  
Nsclc Patients ◽  
Egfr Tki

e14545 Background: Preclinical studies showed the synergistic effect of entinostat with epidermal growth factor tyrosine kinase inhibitors (EGFR-TKI) in NSCLC cell lines. Entinostat (SNDX-275, Syndax Pharmaceuticals) is an oral, class 1 isoform selective HDACi that restores the expression of e-cadherin and sensitivity to EGFR-TKI in NSCLC cell lines. The aim of this study was to determine the safety and feasibility of combining entinostat with erlotinib in advanced NSCLC patients in order to determine the recommended Phase 2 dose. Methods: Patients with recurrent or metastatic NSCLC whose tumors progressed on prior chemotherapy were treated with either 5 or 10mg orally of entinostat once every two weeks and erlotinib 150mg daily. Results: A total of 9 patients were enrolled (3 at entinostat 5mg; 6 at 10mg). Characteristics: Sex: M/F: 6/3; Age range: 46–84 yrs; ECOG PS: 0–1; Smoking status: 1/8 (never/current or prior smokers); Number of prior treatments: 1–2. There was one DLT of grade 3 asthenia. This occurred in one of the six patients in the 10mg dose cohort. The most common adverse events were anorexia, and asthenia. This was more often noted in elderly patients. Of the 9 evaluable patients, one patient had a confirmed partial response and remains on study (>5 cycles) and another patient had stable disease for 8 months. Pharmacokinetic analysis has been completed with both drugs exhibiting levels comparable to historical data. No drug:drug interaction was observed. EGFR FISH, EGFR mutation, and epithelial-to-mesenchymal marker analysis is in progress. Conclusions: This study has established the safety and a recommended phase 2 dose of 10 mg of entinostat once every other week in combination with 150 mg daily of erlotinib in a 28-day cycle in advanced NSCLC patients. A randomized, double blinded phase 2 study has been initiated with 43 patients enrolled to date. [Table: see text]

Utility of the Lung Immune Prognostic Index (LIPI) in prognostication and disease control prediction in advanced NSCLC patients treated with nivolumab.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20645-e20645
Author(s):  
Juan Ruiz Bañobre ◽  
María C. Areses Manrique ◽  
Rosario García Campelo ◽  
Rafael Lopez ◽  
Francisco J. Afonso Afonso ◽  
...  
Keyword(s):  
Disease Control ◽  
Advanced Nsclc ◽  
Smoking Status ◽  
Statistical Significance ◽  
Prognostic Index ◽  
Rank Test ◽  
Clinicopathologic Characteristics ◽  
Logistic Regression Models ◽  
Nsclc Patients ◽  
The Impact

e20645 Background: The lung immune prognostic index (LIPI) has been proposed as a new biomarker to select advanced non-small cell lung cancer (NSCLC) patients for anti-programmed cell death-1 or programmed death ligand 1 therapy. In this study, we investigate the prognostic and predictive utility of the LIPI in a multicentric nivolumab monotherapy-based cohort. Methods: 153 patients with available baseline LIPI were included. Survival estimates were calculated by the Kaplan-Meier method, and groups were compared with the log-rank test. The impact of the baseline LIPI on survival (PFS and OS), and DCR and ORR was assessed by Cox and logistic regression models respectively, adjusted for age, sex, ECOG-PS, smoking status, histology, TNM stage at diagnosis, presence of brain metastases and number of prior regimens. All p values were 2-sided, and those less than 0.05 were considered statistically significant. Results: 50.3% (n = 77) of the patients had a good (0 factors) LIPI, while 41.2% (n = 63) and 8.5% (n = 13) had intermediate (1 factor) and poor (2 factors) LIPI respectively. No significant differences were observed between the LIPI groups according to clinicopathologic characteristics. A high LIPI was significantly associated with poor OS in univariate (HR = 3.12, 95% CI 2.12 – 4.60; p < 0.0001) and multivariate (HR = 3.10, 95% CI 2.09 – 4.58; p < 0.0001) analyses. A high LIPI was associated with poor PFS (HR = 1.49, 95% CI 1.07 – 2.07; p = 0.02), but this correlation did not reach a statistical significance in multivariate analysis (HR = 1.37, 95% CI 0.98 – 1.92; p = 0.07). A higher LIPI was associated with a lower disease control rate in univariate (OR = 0.50, 95% CI 0.29 – 0.85; p = 0.01) and multivariate (OR = 0.55, 95% CI 0.31 – 0.98; p = 0.04) analyses. Conclusions: This study confirms the utility of the LIPI in prognostication and disease control prediction in advanced NSCLC patients treated with nivolumab in the second line of therapy or beyond.

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