Surgical Outcomes After Neoadjuvant Chemoimmunotherapy for Resectable Non-Small Cell Lung Cancer

BackgroundNeoadjuvant chemoimmunotherapy for resectable non-small cell lung cancer (NSCLC) represents an important research topic. Despite the potential benefits of this approach, the inflammatory responses and adverse events associated with neoadjuvant chemoimmunotherapy can present technical challenges and compromise a planned resection. This study assessed the safety and feasibility of neoadjuvant chemoimmunotherapy followed by surgery for resectable NSCLC.MethodsThe study was conducted from May 2019 to March 2021. Patients who were age 18 years or older, were diagnosed with stage Ib–IIIb NSCLC, and received neoadjuvant chemoimmunotherapy followed by surgery were included. Demographic information, clinical and pathologic characteristics, data about neoadjuvant therapy, and surgical details were collected by retrospective chart review. Toxicity profiles were collected retrospectively or by telephone follow-up.ResultsTwenty patients were included in this study. The median age was 56 years (range, 48–72 years), and 18 patients (90%) were men. Squamous carcinoma (14/20, 70%) was the most common cancer type, followed by adenocarcinoma (4/20, 20%), adenosquamous carcinoma (1/20, 5%), and large cell neuroendocrine carcinoma (1/20, 5%). All patients received two to four cycles of neoadjuvant therapy, and the median interval between final therapy and surgery was 49 days (range, 23–133 days). Computed tomography evaluation after neoadjuvant therapy showed partial response in 15 patients (75%) and stable disease in 5 (25%). Final pathologic examinations showed major pathologic response in eight patients, including pathologic complete response in five (25%). Most patients (18/20, 90%) had reduced pathologic staging. Twelve patients (60%) underwent open thoracotomy; the other eight patients underwent minimally invasive surgery, which was uneventful and without intraoperative conversion to open thoracotomy. No perioperative deaths occurred, and only seven patients (35%) developed postoperative complications. Most patients experienced only grade 1–2 adverse effects and laboratory abnormalities during neoadjuvant therapy, and no grade 3 or worse adverse effects or laboratory abnormalities occurred. No patients experienced surgical delays as a result of immune-related adverse events.ConclusionsPreoperative administration of chemoimmunotherapy for patients with resectable NSCLC was safe and feasible.

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Safety and efficacy analysis of pembrolizumab dosing patterns in patients with advanced melanoma and non-small cell lung cancer

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155220984252 ◽

2021 ◽

pp. 107815522098425

Author(s):

A Kartolo ◽

R Holstead ◽

W Hopman ◽

L Young ◽

T Baetz

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Adverse Events ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Treatment Efficacy ◽

Advanced Melanoma ◽

Small Cell ◽

Cancer Type ◽

Small Cell Lung

Aim To evaluate the impact of discrepancy between prescribed and recommended fixed 200 mg dose (P-F discrepancy) on immune-related adverse events (irAEs) and treatment efficacy in patients with advanced melanoma and NSCLC. Methods This retrospective study included 177 patients with advanced melanoma or non-small cell lung cancer (NSCLC) who received at least one cycle of single-agent pembrolizumab. We defined P-F discrepancy as the differences between prescribed pembrolizumab dose and 200 mg recommended dose, expressed in percentages. Our primary outcome was immune-related adverse events (irAEs), and our secondary outcomes included overall survival (OS) and progression free survival (PFS). Results The median P-F discrepancy was –21.5%, with the 25th and 75th percentile at –32% and –5.0% respectively. ROC curve analyses did not show any optimal cutoffs to prognosticate irAEs (AUC = 0.558 for all patients) or cancer mortality (AUC = 0.583 for melanoma; AUC = 0.539 for NSCLC) in either cancer type. Separate multivariable Cox analyses suggested no statistically significant association between P-F discrepancy and overall survival in patients with melanoma (HR 1.012, 95%CI 0.987–1.038, P = 0.362) or NSCLC (HR 0.998, 95%CI 0.978–1.019, P = 0.876). Conclusion There was no optimal pembrolizumab cut-off point to predict irAEs or treatment efficacy. We supported the use of weight-based pembrolizumab dosing, given the potential cost-saving and no differences in terms of irAEs or treatment efficacy in patients with advanced melanoma or NSCLC. Future studies on province- or national-level would be important to validate our findings.

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Do endocrine adverse events predict longer progression-free survival among patients with non-small-cell lung cancer receiving nivolumab?

PLoS ONE ◽

10.1371/journal.pone.0257484 ◽

2021 ◽

Vol 16 (9) ◽

pp. e0257484

Author(s):

Izabela Chmielewska ◽

Marta Dudzińska ◽

Michał Szczyrek ◽

Joanna Świrska ◽

Kamila Wojas-Krawczyk ◽

...

Keyword(s):

Lung Cancer ◽

Adverse Effects ◽

Adverse Events ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Progression Free Survival ◽

Small Cell ◽

Small Cell Lung ◽

Free Survival ◽

Increased Risk

The aim of the study was to assess the occurrence and nature of immune-related endocrine adverse events (irAEs) among patients with non-small-cell lung cancer (NSCLC) treated with nivolumab. Methods: The study group included 35 patients (15 women, 20 men, 65.8 ± 7.1 years) with NSCLC in stage IIIB (n = 16, 45.7%) and IV (n = 19,54.3%) who were treated with nivolumab. Results: Of the studied patients, 34.3% (n = 12) developed endocrine irAEs (irAE group): 22.9% (n = 8) hyperthyroidism and 8.6% (n = 3) hypothyroidism, and in one case, hypophysitis was observed. The median irAEs onset time was 2 months. In the group of patients with thyroid disorders, permanent hypothyroidism eventually developed in 58.3%. The severity of the analyzed irAEs ranged from mild to moderate (Grade 1–2); the case of hypophysitis was estimated as Grade 3. The comparison of progression-free survival time (PFS) between the two groups showed longer PFS in patients in the irAE group (p = 0.021). Patients with irAE were treated significantly longer with nivolumab and they received more doses of nivolumab, however in Cox analysis we did not find patients with irAE to experience progression later than patients without them. Conclusions: Nivolumab therapy is associated with an increased risk of endocrine adverse effects, particularly thyroid dysfunction. Endocrine adverse effects can be successfully treated pharmacologically and usually do not require discontinuation of immunotherapy. The relationship between a better cancer prognosis in patients who developed endocrine irAE has not been found.

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Adjuvant and neoadjuvant therapy for early stage non[ndash ]small cell lung cancer

Seminars in Oncology ◽

10.1053/sonc.2001.27612 ◽

2001 ◽

Vol 28 (4L) ◽

pp. 23-28

Author(s):

Katherine M.W. Pisters

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Neoadjuvant Therapy ◽

Cell Lung Cancer ◽

Early Stage ◽

Small Cell ◽

Small Cell Lung ◽

Adjuvant And Neoadjuvant Therapy

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

Cancer Control ◽

10.1177/1073274820985790 ◽

2021 ◽

Vol 28 ◽

pp. 107327482098579

Author(s):

Kengo Umehara ◽

Kaori Yama ◽

Keisuke Goto ◽

Azusa Wakamoto ◽

Tae Hatsuyama ◽

...

Keyword(s):

Lung Cancer ◽

Adverse Events ◽

Small Cell Lung Cancer ◽

Survival Time ◽

Cell Lung Cancer ◽

Objective Response ◽

Small Cell ◽

Control Group ◽

Small Cell Lung ◽

Corticosteroid Administration

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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