Effect of Systemic Corticosteroid Therapy on the Efficacy and Safety of Nivolumab in the Treatment of Non-Small-Cell Lung Cancer

Introduction: Corticosteroids are used to treat immune-related adverse events (irAEs) associated with nivolumab. However, patients with non-small-cell lung cancer who are administered corticosteroids before the initiation of nivolumab treatment are commonly excluded from clinical trials. The appropriate timing for corticosteroid administration in relation to nivolumab treatment, effects of corticosteroids on the efficacy of nivolumab, and resulting adverse events are not clearly understood. In this study, the effects of differences in the timing of corticosteroid administration on nivolumab efficacy and the resulting adverse events were examined. Methods: A retrospective study was conducted with 109 patients who were treated with nivolumab at Sapporo Minami-Sanjo Hospital between December 2015 and March 2018. Results: Of the 109 patients treated with nivolumab, 12 patients were administered corticosteroids before the first cycle of nivolumab (pre-CS), and 33 patients were administered corticosteroids after the first cycle of nivolumab (post-CS). These 2 groups were compared with the control group comprising 64 patients who were not administered corticosteroids (non-CS). The objective response rate in the post-CS group was significantly higher than that in the non-CS group, and the disease control rate in the pre-CS group was significantly lower than that in the non-CS group. The overall survival time and progression-free survival time in the pre-CS group were significantly shorter than those observed in the non-CS group; however, these did not differ from those in the post-CS group. Conclusions: These results suggest that corticosteroids administered to patients with non-small-cell lung cancer after initiation of nivolumab treatment did not affect the disease prognosis. Thus, corticosteroids can be administered immediately for rapid treatment of irAEs.

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Randomized, Phase III Trial of First-Line Figitumumab in Combination With Paclitaxel and Carboplatin Versus Paclitaxel and Carboplatin Alone in Patients With Advanced Non–Small-Cell Lung Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2013.54.4932 ◽

2014 ◽

Vol 32 (19) ◽

pp. 2059-2066 ◽

Cited By ~ 84

Author(s):

Corey J. Langer ◽

Silvia Novello ◽

Keunchil Park ◽

Maciej Krzakowski ◽

Daniel D. Karp ◽

...

Keyword(s):

Lung Cancer ◽

Adverse Events ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Objective Response ◽

Small Cell ◽

Phase Iii ◽

Small Cell Lung ◽

First Line ◽

Serious Adverse Events

Purpose Figitumumab (CP-751,871), a fully human immunoglobulin G2 monoclonal antibody, inhibits the insulin-like growth factor 1 receptor (IGF-1R). Our multicenter, randomized, phase III study compared figitumumab plus chemotherapy with chemotherapy alone as first-line treatment in patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods Patients with stage IIIB/IV or recurrent NSCLC disease with nonadenocarcinoma histology received open-label figitumumab (20 mg/kg) plus paclitaxel (200 mg/m2) and carboplatin (area under the concentration-time curve, 6 mg · min/mL) or paclitaxel and carboplatin alone once every 3 weeks for up to six cycles. The primary end point was overall survival (OS). Results Of 681 randomly assigned patients, 671 received treatment. The study was closed early by an independent Data Safety Monitoring Committee because of futility and an increased incidence of serious adverse events (SAEs) and treatment-related deaths with figitumumab. Median OS was 8.6 months for figitumumab plus chemotherapy and 9.8 months for chemotherapy alone (hazard ratio [HR], 1.18; 95% CI, 0.99 to 1.40; P = .06); median progression-free survival was 4.7 months (95% CI, 4.2 to 5.4) and 4.6 months (95% CI, 4.2 to 5.4), respectively (HR, 1.10; P = .27); the objective response rates were 33% and 35%, respectively. The respective rates of all-causality SAEs were 66% and 51%; P < .01). Treatment-related grade 5 adverse events were also more common with figitumumab (5% v 1%; P < .01). Conclusion Adding figitumumab to standard chemotherapy failed to increase OS in patients with advanced nonadenocarcinoma NSCLC. Further clinical development of figitumumab is not being pursued.

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Phase 1b Study of Ramucirumab in Combination With Erlotinib or Osimertinib for Untreated EGFR-mutated Non–small Cell Lung Cancer Patients With Asymptomatic Brain Metastases

10.21203/rs.3.rs-533997/v1 ◽

2021 ◽

Author(s):

Hiroyasu Kaneda ◽

Kenji Sawa ◽

Haruko Daga ◽

Asuka Okada ◽

Yuki Nakatani ◽

...

Keyword(s):

Lung Cancer ◽

Adverse Events ◽

Brain Metastases ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Objective Response ◽

Small Cell ◽

Small Cell Lung ◽

Phase 1B ◽

Grade 3

Abstract Objectives: The study was designed to investigate the safety and tolerability of ramucirumab administered in combination with erlotinib or osimertinib for patients with untreated EGFR-mutated non–small cell lung cancer (NSCLC) and asymptomatic brain metastases, a patient subgroup in which these regimens have remained untested.Materials and methods: This multicenter phase 1b study (RELAY-Brain) consisted of two cohorts with three patients each. The two cohorts were assessed independently of one another and were not compared. Patients whose asymptomatic brain metastases had or had not undergone prior local therapy received ramucirumab (10 mg/kg) every 2 weeks plus either erlotinib (150 mg/day) or osimertinib (80 mg/day) until disease progression or intolerable toxicity. The primary objective of the study was to assess dose-limiting toxicity (DLT), defined as central nervous system (CNS) hemorrhage of grade ³2. Secondary end points included safety profile, objective response (systemic and intracranial), and disease control rate.Results: Six patients were enrolled in the study. Neither DLT nor serious or unexpected adverse events were observed. At the time of this analysis, discontinuation of the study drugs had also not occurred. One treatment-related adverse event of grade ³3 (hypertension of grade 3) was apparent. Common adverse events were generally manageable. The median number of ramucirumab administrations was 18.5 (range, 13 to 31), and there were no detected episodes of CNS hemorrhage. Four patients experienced at least one dose delay for ramucirumab, but there were no dose reductions or omissions for this drug. Five of the six patients showed an objective systemic response. Although only one patient had a measurable CNS lesion at baseline, a confirmed intracranial partial response was observed. Conclusion: Ramucirumab in combination with erlotinib or osimertinib showed promising safety and efficacy for EGFR-mutated NSCLC with brain metastases.Clinical trial registration: Japan Registry of Clinical Trials (jRCTs2051190027)

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Carcinoembryonic antigen: a useful prognostic marker in small-cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1985.3.10.1349 ◽

1985 ◽

Vol 3 (10) ◽

pp. 1349-1354 ◽

Cited By ~ 34

Author(s):

J P Sculier ◽

R Feld ◽

W K Evans ◽

F A Shepherd ◽

G DeBoer ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Carcinoembryonic Antigen ◽

Survival Time ◽

Cell Lung Cancer ◽

Group Performance ◽

Objective Response ◽

Eastern Cooperative Oncology Group ◽

Small Cell ◽

Small Cell Lung

Plasma carcinoembryonic antigen (CEA) was determined in 180 patients with small-cell lung cancer (SCLC) before treatment. An abnormal level (greater than or equal to 6 ng/mL) was found in 34% of patients tested. Patients with extensive disease (39/83) had a significantly higher frequency of abnormal CEA (P = .001) than those with limited disease (22/97). There was a strong correlation between obtaining an objective response--particularly a complete response (P = .00003)--and the absence of an elevated CEA. Patients with an abnormal CEA also had a shorter survival time (P = .0007) and the difference remained statistically significant after logrank adjustment for extent of disease and ECOG (Eastern Cooperative Oncology Group) performance status. There was also a negative correlation between survival time and the quantitative level of CEA. In this series, only the group of patients with normal initial CEA levels included all survivors beyond 2.5 years. We conclude that CEA is a useful prognostic factor in SCLC.

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Sorafenib combined with carboplatin/paclitaxel for advanced non-small cell lung cancer: A phase I subset analysis

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.7194 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 7194-7194 ◽

Cited By ~ 18

Author(s):

J. H. Schiller ◽

K. T. Flaherty ◽

M. Redlinger ◽

K. Binger ◽

J. Eun ◽

...

Keyword(s):

Lung Cancer ◽

Adverse Events ◽

Phase I ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Objective Response ◽

Small Cell ◽

Small Cell Lung ◽

Bleeding Events ◽

Anti Tumor Activity

7194 Background: The EGFR is often overexpressed in advanced non-small-cell lung cancer (NSCLC) - a solid tumor associated with a poor prognosis. Oncogenic k-ras mutations and raised serum VEGF predict poor outcome in NSCLC. In vitro targets of sorafenib include Raf, which is downstream of EGFR and k-ras. Sorafenib also targets the VEGFR-2/-3 tyrosine kinases, involved in tumor angiogenesis. Preclinically, sorafenib targets the tumor and tumor endothelium to inhibit tumor growth. Methods: This subanalysis of a Phase I trial with a Phase II expansion in NSCLC was performed to evaluate the safety (adverse events graded by NCI-CTC 2.0) and preliminary anti-tumor activity (response by RECIST, PFS, TTP) of oral sorafenib combined with carboplatin/paclitaxel in 15 patients with advanced, progressive NSCLC. Carboplatin (AUC 6)/paclitaxel (225 mg/m2) was administered on Day 1, and sorafenib (100, 200, or 400 mg bid) on Days 2–18 of each 21-day treatment cycle. Results: Drug-related adverse events were reported by 73% (11/15) of patients, but were mostly grade 1–2 (53%) in severity; none was grade 4. The most common drug-related events at any grade were dermatologic (Hand-foot skin reaction [20%]; rash [60%]), and gastrointestinal (diarrhea [20%]; anorexia [13%]). There were no drug-related cardiovascular adverse events. Three patients reported grade 1–2 drug-related bleeding events (epistaxis n = 2; other n = 1). Of the 14 evaluable patients, four (29%) had a confirmed PR as best response, seven (50%) had SD, and three (21%) had PD. Therefore, the disease control rate (objective response plus SD) was 79%. Duration of response was 25 weeks. Median PFS was 34 weeks. Discussion: This sorafenib combination was well tolerated and showed promising preliminary anti-tumor activity in patients with advanced, progressive NSCLC. [Table: see text]

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Nimotuzumab plus chemotherapy versus chemotherapy alone in advanced non-small cell lung cancer: A phase II, open-label, multicenter, randomized study.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.8053 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 8053-8053

Author(s):

Kumar Prabhash ◽

Kanaka Govind Babu ◽

Ashok K. Vaid ◽

Ranga Rao Rangaraju ◽

Bhawna Sirohi ◽

...

Keyword(s):

Lung Cancer ◽

Adverse Events ◽

Small Cell Lung Cancer ◽

Phase Ii ◽

Cell Lung Cancer ◽

Small Cell ◽

Control Group ◽

Small Cell Lung ◽

Open Label ◽

Nsclc Patients

8053 Background: To evaluate the safety and efficacy of nimotuzumab in combination with chemotherapy (docetaxel and carboplatin) versus chemotherapy alone in stage IIIB/IV non-small cell lung cancer (NSCLC) patients. Methods: This multicenter, open-label, phase II study, randomized 110 patients to receive nimotuzumab plus chemotherapy (nimotuzumab group) or chemotherapy alone (control group), and comprised concomitant, maintenance, and follow-up phases. Nimotuzumab (200 mg) was administered once weekly for 13 weeks during the first 2 phases with 4 cycles of chemotherapy; docetaxel (75 mg/m2) and carboplatin (area under the curve [AUC] = 5 mg/ml*min), every 3 weeks for a maximum of 4 cycles during the concomitant phase. The primary endpoint was objective response rate (ORR; sum of complete response [CR] and partial response [PR]). Secondary endpoints, overall survival (OS), and progression-free survival (PFS) were estimated using Kaplan-Meier method. Efficacy was evaluated on the intent-to-treat (ITT) and efficacy-evaluable (EE) sets. Safety was assessed from adverse events (AEs) and serious adverse events (SAEs) data. Results: ORR was significantly higher in the nimotuzumab group than in the control group in the ITT (54% vs. 34.5%; P=0.04) population. CR and PR were achieved in 3.6% and 50% patients, respectively, in the nimotuzumab group, and in 4% and 30.9% patients, respectively, in the control group. No significant differences in median PFS and OS were observed. Safety profiles were comparable between the 2 groups. Conclusions: Nimotuzumab plus chemotherapy significantly improved ORR as compared to chemotherapy alone; the combination was safe and well tolerated in stage IIIB/IV NSCLC patients.

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Efficacy and Safety of Antigen-specific Immunotherapy in the Treatment of Patients with Non-small-cell Lung Cancer: A Systematic Review and Meta-analysis

Current Cancer Drug Targets ◽

10.2174/1568009618666180430124738 ◽

2019 ◽

Vol 19 (3) ◽

pp. 199-209 ◽

Cited By ~ 1

Author(s):

Bing-Di Yan ◽

Xiao-Feng Cong ◽

Sha-Sha Zhao ◽

Meng Ren ◽

Zi-Ling Liu ◽

...

Keyword(s):

Lung Cancer ◽

Systematic Review ◽

Adverse Events ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Specific Immunotherapy ◽

Meta Analysis ◽

Small Cell ◽

Efficacy And Safety ◽

Small Cell Lung

Background and Objective: We performed this systematic review and meta-analysis to assess the efficacy and safety of antigen-specific immunotherapy (Belagenpumatucel-L, MAGE-A3, L-BLP25, and TG4010) in the treatment of patients with non-small-cell lung cancer (NSCLC). Methods: A comprehensive literature search on PubMed, Embase, and Web of Science was conducted. Eligible studies were clinical trials of patients with NSCLC who received the antigenspecific immunotherapy. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated for overall survival (OS), progression-free survival (PFS). Pooled risk ratios (RRs) were calculated for overall response rate (ORR) and the incidence of adverse events. Results: In total, six randomized controlled trials (RCTs) with 4,806 patients were included. Pooled results showed that, antigen-specific immunotherapy did not significantly prolong OS (HR=0.92, 95%CI: 0.83, 1.01; P=0.087) and PFS (HR=0.93, 95%CI: 0.85, 1.01; P=0.088), but improved ORR (RR=1.72, 95%CI: 1.11, 2.68; P=0.016). Subgroup analysis based on treatment agents showed that, tecemotide was associated with a significant improvement in OS (HR=0.85, 95%CI: 0.74, 0.99; P=0.03) and PFS (HR=0.70, 95%CI: 0.49, 0.99, P=0.044); TG4010 was associated with an improvement in PFS (HR=0.87, 95%CI: 0.75, 1.00, P=0.058). In addition, NSCLC patients who were treated with antigen-specific immunotherapy exhibited a significantly higher incidence of adverse events than those treated with other treatments (RR=1.11, 95%CI: 1.00, 1.24; P=0.046). Conclusion: Our study demonstrated the clinical survival benefits of tecemotide and TG4010 in the treatment of NSCLC. However, these evidence might be limited by potential biases. Therefore, further well-conducted, large-scale RCTs are needed to verify our findings.

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P21.07 Immune-Related Adverse Events with Durvalumab Consolidation in a Real-World Cohort of Patients with Non–Small Cell Lung Cancer (NSCLC)

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2021.01.587 ◽

2021 ◽

Vol 16 (3) ◽

pp. S366

Author(s):

G. Bravo Montenegro ◽

M. Serzan ◽

A. Belouali ◽

P. Sackstein ◽

K. Chen ◽

...

Keyword(s):

Lung Cancer ◽

Adverse Events ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Real World ◽

Small Cell ◽

Small Cell Lung

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440 Activity and safety of camrelizumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced non-small-cell lung cancer

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0440 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A466-A466

Author(s):

Guo Gui Sun ◽

Jing Hao Jia ◽

Peng Gao ◽

Xue Min Yao ◽

Ming Da Chen ◽

...

Keyword(s):

Lung Cancer ◽

Adverse Events ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Advanced Nsclc ◽

Small Cell ◽

Large Sample Size ◽

Small Cell Lung ◽

Previously Treated ◽

Line Chemotherapy

BackgroundEffective options are limited for patients with non–small-cell lung cancer (NSCLC) whose disease progresses after first-line chemotherapy. Camrelizumab is a potent anti-PD-1 monoclonal antibody and has shown promising activity in NSCLC. We assessed the activity and safety of camrelizumab for patients with previously treated, advanced NSCLC patients with negative oncogenic drivers.MethodsPatients who progressed during or following platinum-based doublet chemotherapy were enrolled. All patients received camrelizumab(200 mg)every 3 weeks or in combination with chemotherapy until loss of clinical benefit. The primary endpoint was objective response rate (ORR), other endpoints included disease control rate (DCR), progression-free survival (PFS) and safety.ResultsBetween Aug 5, 2019, and Jun 19, 2020, we enrolled 29 patients, 25 patients were available evaluated, ORR and DCR was 36% (9/25) and 92% (23/25), respectively. 25 of 29 patients were still receiving the treatment, the median PFS was not yet achieved. Compared with those without reactive cutaneous capillary endothelial proliferation (RCCEP), patients with RCCEP had higher ORR (60% vs. 28.6%). Treatment-related adverse events (AEs) occurred in 69.0% of patients (all Grade), and the most common were RCCEP (37.9%), pneumonitis (6.9%), and chest congestion (6.9%). Treatment-related grade 3 to 4 adverse events occurred in 10.3% of patients.ConclusionsIn patients with previously treated advanced NSCLC, camrelizumab demonstrated improved ORR and DCR, compared with historical data of the 2nd line chemotherapy, with a manageable safety profile. While patients with RCCEP derived greater benefit from camrelizumab. Further studies are needed in large sample size trials.

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Selpercatinib in RET fusion-positive non-small-cell lung cancer (SIREN): a retrospective analysis of patients treated through an access program

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211019675 ◽

2021 ◽

Vol 13 ◽

pp. 175883592110196

Author(s):

Oliver Illini ◽

Maximilian Johannes Hochmair ◽

Hannah Fabikan ◽

Christoph Weinlinger ◽

Amanda Tufman ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Real World ◽

Objective Response ◽

Progression Free Survival ◽

Small Cell ◽

Small Cell Lung ◽

Real World Setting ◽

Access Program

Introduction: Rearranged during transfection (RET) gene fusions are rare genetic drivers in non-small cell lung cancer (NSCLC). Selective RET-inhibitors such as selpercatinib have shown therapeutic activity in early clinical trials; however, their efficacy in the real-world setting is unknown. Methods: A retrospective efficacy and safety analysis was performed on data from RET fusion-positive NSCLC patients who participated in a selpercatinib access program (named patient protocol) between August 2019 and January 2021. Results: Data from 50 patients with RET fusion-positive advanced NSCLC treated with selpercatinib at 27 centers in 12 countries was analyzed. Most patients were Non-Asian (90%), female (60%), never-smokers (74%), with a median age of 65 years (range, 38–89). 32% of the patients had known brain metastasis at the time of selpercatinib treatment. Overall, 13 patients were treatment-naïve, while 37 were pretreated with a median of three lines of therapy (range, 1–8). The objective response rate (ORR) was 68% [95% confidence interval (CI), 53–81] in the overall population. The disease control rate was 92%. The median progression-free survival was 15.6 months (95% CI, 8.8–22.4) after a median follow-up of 9 months. In patients with measurable brain metastases ( n = 8) intracranial ORR reached 100%. In total, 88% of patients experienced treatment-related adverse events (TRAEs), a large majority of them being grade 1 or 2. The most common grade ⩾ 3 TRAEs were increased liver enzyme levels (in 10% of patients), prolonged QTc time (4%), abdominal pain (4%), hypertension (4%), and fatigue/asthenia (4%). None of patients discontinued selpercatinib treatment for safety reasons. No new safety concerns were observed, nor where there any treatment-related death. Conclusions: In this real-world setting, the selective RET-inhibitor selpercatinib demonstrated durable systemic and intracranial antitumor activity in RET fusion-positive NSCLC and was well tolerated.

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