Gut microbiota serves an important role in shaping systemic immune responses. Antibiotics cause changes in the gut microbiota that may influence the efficacy of cancer immunotherapy. In the present ...study, a retrospective analysis of the data from 90 patients treated with nivolumab for non-small cell lung cancer (NSCLC) was conducted. A total of 13 patients were treated with antibiotics prior to nivolumab therapy. The median progression-free survival time in patients treated with antibiotics was 1.2 months 95% confidence interval (CI), 0.5-5.8, while the time for patients who were not treated with antibiotics was 4.4 months (95% CI, 2.5-7.4). The median overall survival time in patients treated with antibiotics was 8.8 months, while it was not reached in those not treated with antibiotics, respectively. The differences between the survival curves with regard to PFS and OS were statistically significant (P=0.04 and P=0.037, respectively). However, in multivariate analysis, no statistically significant association was indicated between survival and prior antibiotic use, although a certain trend concerning the negative influence of antibiotic use was conveyed.
Objectives
Although liver metastasis has been known to be associated with poor prognosis, only a few studies have shown an association between liver metastasis and treatment outcomes with immune ...checkpoint inhibitors (ICI). Furthermore, factors associated with prognosis have remained unclear. The present study therefore evaluates the efficacy of nivolumab, pembrolizumab, and atezolizumab among patients with non-small cell lung cancer (NSCLC) who had liver metastasis and identifies factors correlated with prognosis.
Materials and methods
A total of 215 patients with advanced and recurrent NSCLC who received ICI therapy at a single center were retrospectively reviewed. A total of 41 patients (19.1%) had liver metastasis upon initiation of ICI therapy. Overall, 125, 64, and 26 patients were treated with nivolumab, pembrolizumab, and atezolizumab, respectively.
Results
Among the included patients, those with liver metastasis had shorter overall survival (OS) hazard ratio (HR), 2.04; 95% CI 1.33–3.13 and progression-free survival (PFS) (HR, 1.89; 95% CI 1.29–1.71) compared to those without the same. Patients with liver metastasis had a response rate (RR) of 22.5%. Among patients with liver metastasis, inferior OS was associated with low albumin, poor Eastern Cooperative Oncology Group performance status, driver mutation, and number of liver metastasis (≥ 5). Moreover, patients with liver metastasis who had good Royal Marsden Hospital (0–1) and Gustave Roussy Immune (0–1) scores showed significantly longer OS and PFS.
Conclusion
Despite the poor outcomes with ICI treatment in patients with advanced and recurrent NSCLC who had liver metastasis, some characteristics among patients with liver metastasis may be associated with prognosis.
Summary Background With use of EGFR tyrosine-kinase inhibitor monotherapy for patients with activating EGFR mutation-positive non-small-cell lung cancer (NSCLC), median progression-free survival has ...been extended to about 12 months. Nevertheless, new strategies are needed to further extend progression-free survival and overall survival with acceptable toxicity and tolerability for this population. We aimed to compare the efficacy and safety of the combination of erlotinib and bevacizumab compared with erlotinib alone in patients with non-squamous NSCLC with activating EGFR mutation-positive disease. Methods In this open-label, randomised, multicentre, phase 2 study, patients from 30 centres across Japan with stage IIIB/IV or recurrent non-squamous NSCLC with activating EGFR mutations, Eastern Cooperative Oncology Group performance status 0 or 1, and no previous chemotherapy for advanced disease received erlotinib 150 mg/day plus bevacizumab 15 mg/kg every 3 weeks or erlotinib 150 mg/day monotherapy as a first-line therapy until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, as determined by an independent review committee. Randomisation was done with a dynamic allocation method, and the analysis used a modified intention-to-treat approach, including all patients who received at least one dose of study treatment and had tumour assessment at least once after randomisation. This study is registered with the Japan Pharmaceutical Information Center, number JapicCTI-111390. Findings Between Feb 21, 2011, and March 5, 2012, 154 patients were enrolled. 77 were randomly assigned to receive erlotinib and bevacizumab and 77 to erlotinib alone, of whom 75 patients in the erlotinib plus bevacizumab group and 77 in the erlotinib alone group were included in the efficacy analyses. Median progression-free survival was 16·0 months (95% CI 13·9–18·1) with erlotinib plus bevacizumab and 9·7 months (5·7–11·1) with erlotinib alone (hazard ratio 0·54, 95% CI 0·36–0·79; log-rank test p=0·0015). The most common grade 3 or worse adverse events were rash (19 25% patients in the erlotinib plus bevacizumab group vs 15 19% patients in the erlotinib alone group), hypertension (45 60% vs eight 10%), and proteinuria (six 8% vs none). Serious adverse events occurred at a similar frequency in both groups (18 24% patients in the erlotinib plus bevacizumab group and 19 25% patients in the erlotinib alone group). Interpretation Erlotinib plus bevacizumab combination could be a new first-line regimen in EGFR mutation-positive NSCLC. Further investigation of the regimen is warranted. Funding Chugai Pharmaceutical Co Ltd.
Background
Based on several phase III studies, immune checkpoint inhibitors (ICIs) are essential and promising drugs for the treatment of non‐small cell lung cancer (NSCLC). However, in patients ...previously treated with ICI, the efficacy and safety of rechallenging the same or another type of ICI inhibitor remain unclear. Moreover, clinical data about the efficacy of switching the administration of anti‐programmed death‐1 (PD‐1) antibodies (e.g. nivolumab, pembrolizumab) and anti‐programmed death‐ligand 1 (PD‐L1) antibodies (e.g. atezolizumab) as ICI rechallenge are limited. Thus, the current study aimed to evaluate the efficacy and safety of such treatment strategy in NSCLC patients.
Methods
We retrospectively reviewed the medical records of 17 patients with advanced or recurrent NSCLC who received both anti‐PD‐1 and anti‐PD‐L1 antibodies during their clinical courses.
Results
Among the 17 patients, one (5.9%) and nine (52.9%) achieved partial response and stable disease, respectively, after ICI rechallenge. The median progression‐free survival of ICI rechallenge in these patients was 4.0 (range: 0.4–8.0) months, and the median overall survival from the start of the initial ICI was 31.0 (range: 7.6–46.8) months. Of the 10 patients who developed immune‐related adverse events (irAEs) during the first ICI treatment, five presented with these events after the readministration of ICI. Among them, four experienced relapsed irAEs and two patients had pneumonitis, which is a grade 3 or higher irAE. Almost all irAEs during the rechallenge treatment were manageable.
Conclusions
Switching the administration of anti‐PD‐1 and anti‐PD‐L1 antibodies as ICI rechallenge could be a treatment option for some NSCLC patients.
Key points
• Significant findings of the study
In this study, switching the administration of anti‐PD‐1 and anti‐PD‐L1 antibodies as ICI rechallenge could be an effective and safe treatment option for some patients with advanced or recurrent NSCLC.
• What this study adds
Switching the administration of ICI may increase the efficacy of readministration. However, the mechanism is unknown. Thus, further accumulation of cases is required, and extensive investigations must be conducted to elucidate the mechanism and benefits of such treatment.
Thymic carcinoma (TC) is a rare cancer with a poor prognosis and limited treatment options, especially after relapse.
In this open-label, two-stage, multicentre, single-arm and phase II trial, the ...main eligibility criteria were unresectable or recurrent TC, an Eastern Cooperative Oncology Group–performance status of 0 or 1, progression after at least one chemo(radio)therapy and no history of autoimmune disease. Nivolumab was administered at a dose of 3 mg/kg every 2 weeks. The primary end-point was response rate (RR) as evaluated by central review using Response Evaluation Criteria In Solid Tumours (RECIST), version 1.1. The planned sample size was 15 for each stage, with a threshold RR of 5%, an expected RR of 20%, one-sided alpha of 5% and power of 80%.
Between July 1 and August 16 2016, 15 patients were accrued in the first stage. Response was assessable in all patients, and 13 had squamous histology. Median follow-up time was 14.1 months (range: 2.4–17.5). The median number of nivolumab received was eight (range: 3–33). RR was 0% (95% confidential interval CI: 0–21.8). Eleven patients had stable disease (SD) including five patients with SD for 24 or more weeks. Median progression-free survival was 3.8 months (95% CI: 1.9–7.0). Two patients experienced immune-related serious adverse events (grade III aspartate aminotransferase (AST) increase and grade II adrenal insufficiency). Because the early termination criteria (less than one responder) were fulfilled during the first stage, the patient accrual was terminated.
Despite the small number of patients, nivolumab was unable to produce tumour shrinkage by RECIST in previously treated unresectable or recurrent TC.
•Thymic carcinoma (TC) is a rare cancer with a poor prognosis and limited treatment options.•This is the first phase II trial of nivolumab for pretreated unresectable or recurrent TC.•Nivolumab produced no responders among the 15 patients accrued during the first stage.•Only two patients developed serious immune-related adverse events, both of which were resolved.•However, the disease control rate of 73% suggested some clinical benefit of nivolumab in TC.
Biomarkers for predicting the effect of anti–programmed cell death 1 monoclonal antibody therapy against non–small-cell lung cancer (NSCLC) are urgently required. We prospectively studied the ...baseline plasma soluble programmed cell death ligand 1 (sPD-L1) levels from 39 NSCLC patients as a predictive marker of nivolumab therapy. The clinical benefit from nivolumab therapy was significantly associated with the baseline plasma sPD-L1 levels. Plasma sPD-L1 levels could represent a novel predictive marker for nivolumab therapy against NSCLC.
Biomarkers for predicting the effect of anti–programmed cell death 1 (PD-1) monoclonal antibody against non–small-cell lung cancer (NSCLC) are urgently required. Although it is known that the blood levels of soluble programmed cell death ligand 1 (sPD-L1) are elevated in various malignancies, the nature of sPD-L1 has not been thoroughly elucidated. We investigated the significance of plasma sPD-L1 levels as a biomarker for anti–PD-1 monoclonal antibody, nivolumab therapy.
The present prospective study included 39 NSCLC patients. The patients were treated with nivolumab at the dose of 3 mg/kg every 2 weeks, and the effects of nivolumab on NSCLC were assessed according to the change in tumor size, time to treatment failure (TTF), and overall survival (OS). The baseline plasma sPD-L1 concentration was determined using an enzyme-linked immunosorbent assay.
The area under the curve of the receiver operating characteristic curve was 0.761. The calculated optimal cutoff point for sPD-L1 in the plasma samples was 3.357 ng/mL. Of the 39 patients, 59% with low plasma sPD-L1 levels achieved a complete response or partial response and 25% of those with high plasma sPD-L1 levels did so. In addition, 22% of the patients with low plasma sPD-L1 levels developed progressive disease compared with 75% of those with high plasma sPD-L1 levels. The TTF and OS were significantly longer for those patients with low plasma sPD-L1 levels compared with the TTF and OS for those with high plasma sPD-L1 levels.
The clinical benefit from nivolumab therapy was significantly associated with the baseline plasma sPD-L1 levels. Plasma sPD-L1 levels might represent a novel biomarker for the prediction of the efficacy of nivolumab therapy against NSCLC.
Purpose
Polypharmacy is a common problem among older adults. However, its prevalence and impact on the clinical outcomes of anticancer treatment, such as survival and adverse events, in older ...patients with advanced cancer have not been well investigated.
Methods
We retrospectively reviewed data from Japanese patients treated with an immune checkpoint inhibitor (ICI) for advanced or recurrent non-small-cell lung cancer (NSCLC) between 2016 and 2019.
Results
Among 157 older (aged ≥ 65 years) patients, the prevalence of polypharmacy, defined as ≥ 5 medications, was 59.9% (94/157). The prevalence of potentially inappropriate medication use, according to the screening tool of older people’s prescription (STOPP) criteria version 2, was 38.2% (60/157). The median progression-free survival (PFS) in patients with and without polypharmacy was 3.7 and 5.5 months, respectively (
P
= 0.0017). The median overall survival (OS) in patients with and without polypharmacy was 9.5 and 28.1 months, respectively (
P
< 0.001). Multivariate analysis revealed marked associations between polypharmacy and OS, but no significant associations between polypharmacy and PFS. Polypharmacy was not associated with immune-related adverse events but was associated with higher rate of unexpected hospitalizations during ICI treatment (59.6% vs. 31.7%,
P
< 0.001).
Conclusion
Polypharmacy is an independent prognostic factor in older patients with advanced NSCLC treated with ICI. Also, polypharmacy could be utilized as a simple indicator of patients’ comorbidities and symptoms or as a predictive marker of unexpected hospitalizations during ICI treatment.
Immune-related adverse events, including autoimmune toxicity, may develop as a consequence of immune-checkpoint inhibitor (ICI) cancer therapy. Cytokine release syndrome (CRS) is a severe and ...life-threatening cytokine-associated toxicity that can develop after adoptive T-cell therapy. We herein report a rare case of severe CRS after ICI therapy for advanced non-small-cell lung cancer. He presented with a prolonged high fever, cardiogenic shock, and disseminated intravascular coagulation after the first course of programed death ligand-1 inhibitor and platinum-based doublet chemotherapy. He recovered by steroid pulse therapy and tocilizumab. CRS is a rare but life-threatening adverse event of ICI therapy and therefore warrants awareness.
An individual may contract coronavirus disease 2019 (COVID-19) and influenza simultaneously; hence, adequate measures must be undertaken for the next winter in Japan. In preparation for the future, ...this study aimed to clarify the incidence of influenza coinfection in patients with COVID-19 during the previous winter. We conducted a retrospective study of the medical records of 193 patients diagnosed with COVID-19 between January 31, 2020, and April 23, 2020, in a single hospital. We evaluated the incidence of COVID-19 and influenza coinfection. Using rapid diagnostic testing, we found that no patient with COVID-19 was coinfected with influenza. Coinfection with influenza and COVID-19 was rare during the past winter in Japan.
Advanced thymic carcinomas have limited treatment options. Recently, lenvatinib was approved for advanced thymic carcinoma treatment. However, the clinical benefit of lenvatinib re‐administration in ...patients with advanced thymic carcinoma who developed prior lenvatinib treatment resistance (lenvatinib rechallenge) remains unclear. Here, we present a case treated with lenvatinib rechallenge for advanced thymic carcinoma who was previously treated with lenvatinib as the second‐line treatment followed by multiple cytotoxic agents. Disease control rapidly deteriorated after the eighth line of treatment because of uncontrollable right pleural and pericardial effusion, which required repeated thoracic and pericardial drainage. Shortly after lenvatinib re‐administration, rapid pleural and pericardial effusion reduction was observed. Thereafter, the patient achieved sustained clinical response with good pleural and pericardial effusion control for approximately 7 months. Our case might suggest lenvatinib rechallenge as a treatment option for patients with advanced thymic carcinoma, especially those with poor pleural and pericardial effusion control.
We present a case treated with “lenvatinib rechallenge” for advanced thymic carcinoma who was previously treated with lenvatinib followed by multiple cytotoxic agents. Shortly after lenvatinib rechallenge, rapid pleural and pericardial effusion reduction was observed. Our case might suggest lenvatinib rechallenge as a treatment option for patients with advanced thymic carcinoma.
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