Outcomes in Patients With Non–small-cell Lung Cancer With Brain Metastases Treated With Pembrolizumab-based Therapy

BackgroundPatients with metastatic non–small-cell lung cancer (mNSCLC) and untreated brain metastases (BM) have been excluded from most trials of immune checkpoint inhibitors (ICIs). Real-world evidence on efficacy and survival outcomes of ICIs in patients with BM is limited.Patients and MethodsWe conducted a single-center retrospective study of patients with mNSCLC treated with pembrolizumab with or without chemotherapy and compared progression-free survival (PFS) and overall survival (OS) between patients with and without BM using Kaplan-Meier and Cox methodology. We also characterized systemic and intracranial objective response rate (ORR) and treatment details, including timing of cranial irradiation.ResultsBetween Augutst 2013 and December 2018, 570 patients with mNSCLC treated with pembrolizumab-based therapy were analyzed. Of 126 (22.1%) patients with BM, 96 (76.2%) had treated BM (local therapy prior to pembrolizumab), and 30 (23.8%) had untreated BM. Of patients with untreated BM, 17 (56.7%) underwent radiation within 30 days after pembrolizumab initiation. In the remaining 13 (43.3%) treated with pembrolizumab-based therapy alone, intracranial ORR was 36.4%. Patients with and without BM did not have significantly different systemic ORR (27.8% vs. 29.7%; P = .671), PFS (mPFS 9.2 vs. 7.7 months; P = .609), or OS (mOS 18.0 vs. 18.7 months; P = .966). Factors associated with improved survival on Cox analysis included female gender, performance status, adenocarcinoma histology, and first-line therapy.ConclusionsPatients with BM did not have inferior survival to patients without BM after treatment with pembrolizumab-based therapy. In the current era, BM may not automatically confer inferior survival, and should not exclude patients from receiving pembrolizumab-based therapy.     

Living With Cancer Alone? The Experiences of Singles Diagnosed With Colorectal Cancer

This paper seeks to understand the experiences of single colorectal cancer patients. This study consisted of 12 semi-structured interviews that were digitally voice-recorded, transcribed, and analyzed. Six main themes emerged: (a) gradual shift in view of cancer diagnosis from fatalistic to normalized, (b) perception of cancer as a nadir experience, (c) concerns of singlehood, (d) factors influencing cancer experiences, (e) factors influencing coping with cancer, and (f) range of responses towards cancer diagnosis. Singles with colorectal cancer require short- to long-term individualized care plans, and psycho-emotional support. This may help enhance their individual coping and adjustment to the diagnosis.     

Cell-Free Plasma DNA-Guided Treatment With Osimertinib in Patients With Advanced EGFR-Mutated NSCLC

Introduction

Osimertinib is standard treatment for patients with advanced EGFR T790M-mutated non–small-cell lung cancer who have been pre-treated with EGFR–tyrosine kinase inhibitors (TKIs). We studied whether cell-free plasma DNA for T790M detection can be used to select patients for osimertinib treatment in the clinical routine.

How Do I Deal With the Axilla in Patients With a Positive Sentinel Lymph Node?

Optimal management of the axilla in a patient with a positive sentinel node biopsy is not yet defined.     

Neoadjuvant Chemotherapy With Docetaxel-Cisplatin in Patients With Stage III N2 Non–Small-Cell Lung Cancer

IntroductionTo assess the efficacy and potential prognostic factors of patients with stage III N2 non–small-cell lung cancer (NSCLC) treated with neoadjuvant docetaxel-cisplatin (DP) chemotherapy followed by surgical resection.MethodsSixty-two patients with NSCLC treated with DP as neoadjuvant chemotherapy between November 2003 and December 2009 were identified and reviewed in this study. Tumor response, survival, and clinicopathologic data were collected retrospectively. The time to event was analyzed by fitting Cox proportional hazards models.ResultsFifty-eight (94%) of 62 patients eventually underwent surgical resection after DP. The overall clinical response rate to induction DP chemotherapy was 42%. Patients with squamous cell carcinoma (SCC) histology were more likely to response to the DP regimen than those with adenocarcinoma histology (68% vs. 33%, P = .006). With a median follow-up of 82.4 months among the 58 patients, there were 41 (71%) tumor relapses and 27 (47%) deaths. The median event-free survival was 27.5 months (95% CI, 22.3-32.7 months), and the median overall survival was 66.7 months (95% CI, 35.1-98.3 months). In multivariate analysis, when fitting the Cox proportional hazards model, SCC histology (hazard ratio [HR] 0.234 [95% CI, 0.098-0.560]; P = .001) and mediastinal downstaging to N0 (HR 0.451 [95% CI, 0.226-0.898]; P = .024) were independent predictors of better event-free survival.ConclusionsNeoadjuvant chemotherapy with the DP regimen is both active and well tolerated in patients with stage III N2 NSCLC. SCC histology predicted a better treatment response and survival outcome than adenocarcinoma histology in this patient group. Further investigation of combined-modality treatment is warranted to improve survival in the adenocarcinoma subset of stage III N2 NSCLC.     

Correlation of Neutrophil to Lymphocyte Ratio and Absolute Neutrophil Count With Outcomes With PD-1 Axis Inhibitors in Patients With Advanced Non–Small-Cell Lung Cancer

Introduction

Programmed death-1 (PD-1) axis inhibitors have become standard therapy in advanced non–small-cell lung cancer (NSCLC). Response might be delayed and pseudo-progression occasionally occurs in patients who eventually benefit from treatment. Additional markers beyond programmed death ligand 1 (PD-L1) expression are needed to assist in patient selection, response evaluation, and treatment decisions.

Soluble c-Met Levels Correlated With Tissue c-Met Protein Expression in Patients With Advanced Non–Small-Cell Lung Cancer

Background

Immunohistochemistry (IHC) and fluorescent in situ hybridization are reliable methods for identifying c-Met protein expression or c-Met gene amplification. However, each technique requires a high-quality tissue sample, which might not be available. The aim of the present study was to investigate the correlation between the soluble c-Met level and tissue c-Met protein expression and the relationship between these markers and patient prognosis.

Immune-related Adverse Events of Pembrolizumab in a Large Real-world Cohort of Patients With NSCLC With a PD-L1 Expression ≥ 50% and Their Relationship With Clinical Outcomes

BackgroundThe role of immune-related adverse events (irAEs), as a surrogate predictor of the efficacy of checkpoint inhibitors, has not yet been described in the setting of first-line, single-agent pembrolizumab for patients with metastatic non–small-cell lung-cancer (NSCLC) with a programmed death-ligand 1 (PD-L1) expression of ≥ 50%.Patients and MethodsWe previously conducted a multicenter retrospective analysis in patients with treatment-naive metastatic NSCLC and a PD-L1 expression of ≥ 50% receiving first-line pembrolizumab. Here, we report the results of the irAE analysis and the potential correlation between irAEs and clinical outcomes.ResultsA total of 1010 patients were included in this analysis; after a 6-week landmark selection, 877 (86.8%) patients were included in the efficacy analysis. Any grade irAEs (P < .0001), grade 3/4 irAEs (P = .0025), leading to discontinuation irAEs (P = .0144), multiple-site and single-site irAEs (P < .0001), cutaneous irAEs (P = .0001), endocrine irAEs (P = .0227), pulmonary irAEs (P = .0479), and rheumatologic irAEs (P = .0018) were significantly related to a higher objective response rate. Any grade irAEs (P < .0001), single-site irAEs (P < .0001), multiple-site irAEs (P = .0005), cutaneous irAEs (P = .0042), endocrine irAEs (P < .0001), gastrointestinal irAEs (P = .0391), and rheumatologic irAEs (P = .0086) were significantly related to progression-free survival. Any grade irAEs (P < .0001), single-site irAEs (P < .0001), multiple-site irAEs (P = .0003), cutaneous irAEs (P = .0002), endocrine irAEs (P = .0001), and rheumatologic irAEs (P = .0214) were significantly related to overall survival.ConclusionsThis study confirms the feasibility and the safety of first-line, single-agent pembrolizumab, in a large, real-world cohort of patients with NSCLC with PD-L1 expression ≥ 50%. The occurrence of irAEs may be a surrogate of clinical activity and improved outcomes in this setting.     

Challenges With Serum Protein Electrophoresis in Assessing Progression and Clinical Response in Patients With Waldenström Macroglobulinemia

Accurate determination of the immunoglobulin (Ig) M paraprotein concentration is crucial to evaluating response in patients with Waldenström macroglobulinemia (WM). In most clinical laboratories, M-spike quantitation is performed by serum protein electrophoresis, which is the same method used to quantitate IgG and IgA paraproteins in patients with multiple myeloma (MM). However, the migration pattern and propensity of IgM paraproteins to form higher-order complexes in serum makes laboratory evaluation of samples from patients with WM especially challenging. We review examples of patients whose IgM paraprotein is particularly ill-suited to M-spike quantitation by serum protein electrophoresis: a case of “sticky M,” a case of IgM multimers that cannot be resolved, and a case of an IgM in the β region. In these and similar cases, a method other than M-spike quantitation, such as IgM heavy chain nephelometry, should be considered in laboratory evaluation of paraprotein concentration.     

Distinct MET Protein Localization Associated With MET Exon 14 Mutation Types in Patients With Non–small-cell Lung Cancer

Background

The MET gene has been recognized as a potential important therapeutic target in non–small-cell lung cancer (NSCLC). We sought to investigate the MET exon 14 mutations in a cohort of Chinese patients with NSCLC.

Is There a Flare Phenomenon on Bone Scintigraphy in Men With Advanced Prostate Cancer Treated With Radium-223?

Introduction

Radium-223 is an approved survival-prolonging treatment option in men with castration-resistant prostate cancer (mCRPC) and bone metastases. In the registration trial (ALSYMPCA), no regular imaging was mandated. We aimed to analyze men with metastatic mCRPC treated with radium-223 who had bone scintigraphy for staging and treatment monitoring.

Comparing Outcomes of Patients With Early-Stage Non–Small-Cell Lung Cancer Treated With Stereotactic Body Radiotherapy Based on Frailty Status

Introduction

Frailty of surgical patients has been associated with worse outcomes. There is limited literature discussing frailty in patients with lung cancer treated with stereotactic body radiotherapy (SBRT). This study assesses the relationship between frailty and overall survival (OS), tumor control, and toxicity in patients with early-stage non–small-cell lung cancer (NSCLC) treated with SBRT.

Patient-reported Outcomes After the Treatment of Early Stage Non–small-cell Lung Cancer With Stereotactic Body Radiotherapy Compared With Surgery

IntroductionAs there is increasing evidence for comparable survival after either stereotactic body radiotherapy (SBRT) or surgery for patients with stage I non–small-cell lung cancer (NSCLC), treatment impact on the quality of life (QoL) is essential for well-informed decision-making. Our previous work evaluated health utility between surgery and SBRT in stage I NSCLC. The aim of this secondary analysis is to directly compare QoL in the first year after SBRT and surgery.Materials and MethodsQoL was assessed at baseline and 3, 6, and 12 months after treatment. Two prospectively collected databases of patients with clinically proven stage I NSCLC, from 2 large hospitals in the Netherlands, were pooled (n = 306; 265 patients were treated with SBRT and 41 patients with surgery). To correct for confounding, propensity scores were calculated, to be selected for surgical treatment. A mixed model analysis was used to study differences in QoL between the 2 treatments.ResultsThe 41 surgical patients were matched to 41 SBRT patients on propensity score with a 1:1 ratio. At baseline, patients in the surgery group report a lower QoL compared with patients in the SBRT group. However, during the first year after treatment, no clinical meaningful differences were observed, except for role functioning, between patients treated using either modality.ConclusionThis study comparing a matched cohort revealed no clinically significant differences in QoL following either SBRT or surgery for early stage NSCLC. These results support the hypothesis that surgery and SBRT are comparable treatments.     

Phase 2 Study of Nimotuzumab in Combination With Concurrent Chemoradiotherapy in Patients With Locally Advanced Non–Small-Cell Lung Cancer

BackgroundWe evaluated the tolerability and efficacy of nimotuzumab, a humanized IgG1 monoclonal anti–epidermal growth factor receptor antibody, with concurrent chemoradiotherapy in patients with unresectable locally advanced non–small-cell lung cancer.Patients and MethodsIn this multicenter, single-arm, open-label, phase 2 trial conducted in Japan (JapicCTI-090825), patients received thoracic radiotherapy (60 Gy, 2 Gy per fraction, 6 weeks) and four 4-week cycles of chemotherapy (day 1, cisplatin 80 mg/m²; days 1 and 8, vinorelbine 20 mg/m²). Nimotuzumab 200 mg was administrated weekly for 16 weeks. The primary endpoint was treatment completion rate, defined as the percentage of patients completing 60 Gy of radiotherapy within 8 weeks, 2 cycles of chemotherapy, and at least 75% of the required nimotuzumab dose during the initial 2-cycle concurrent chemoradiotherapy period.ResultsOf 40 patients enrolled, 39 received the study treatment, which was well tolerated, with a completion rate of 87.2%. Thirty-eight patients completed 60 Gy of radiotherapy within 8 weeks. Infusion reaction, grade 3 or higher rash, grade 3 or higher radiation pneumonitis, or grade 4 or higher nonhematologic toxicity were not observed. The objective response rate was 69.2%. The median progression-free survival (PFS) and 5-year PFS rate were 508 days and 29.0%, respectively. The 5-year PFS rate in patients with non–squamous cell carcinoma (n = 23) was 13.7% and in patients with squamous cell carcinoma (n = 16) was 50.0%. The 5-year overall survival rate was 58.4%.ConclusionAddition of nimotuzumab to the concurrent chemoradiotherapy regimen was well tolerated and showed potential for treating patients with locally advanced non–small-cell lung cancer, particularly squamous cell carcinoma.