Complete and timely tissue genotyping is challenging, leading to significant numbers of patients with newly diagnosed metastatic non-small cell lung cancer (mNSCLC) being undergenotyped for all eight ...genomic biomarkers recommended by professional guidelines. We aimed to demonstrate noninferiority of comprehensive cell-free DNA (cfDNA) relative to physician discretion standard-of-care (SOC) tissue genotyping to identify guideline-recommended biomarkers in patients with mNSCLC.
Prospectively enrolled patients with previously untreated mNSCLC undergoing physician discretion SOC tissue genotyping submitted a pretreatment blood sample for comprehensive cfDNA analysis (Guardant360).
Among 282 patients, physician discretion SOC tissue genotyping identified a guideline-recommended biomarker in 60 patients versus 77 cfDNA identified patients (21.3% vs. 27.3%;
< 0.0001 for noninferiority). In tissue-positive patients, the biomarker was identified alone (12/60) or concordant with cfDNA (48/60), an 80% cfDNA clinical sensitivity for any guideline-recommended biomarker. For FDA-approved targets (
) concordance was >98.2% with 100% positive predictive value for cfDNA versus tissue (34/34
or
-positive patients). Utilizing cfDNA, in addition to tissue, increased detection by 48%, from 60 to 89 patients, including those with negative, not assessed, or insufficient tissue results. cfDNA median turnaround time was significantly faster than tissue (9 vs. 15 days;
< 0.0001). Guideline-complete genotyping was significantly more likely (268 vs. 51;
< 0.0001).
In the largest cfDNA study in previously untreated mNSCLC, a validated comprehensive cfDNA test identifies guideline-recommended biomarkers at a rate at least as high as SOC tissue genotyping, with high tissue concordance, more rapidly and completely than tissue-based genotyping.
.
Biosimilars can provide choices for patients and may provide cost savings; however, their uptake has been slow in the USA, in part due to limited knowledge. To provide additional confidence in US ...pegfilgrastim biosimilars, this narrative review compared the safety profiles of biosimilar pegfilgrastims, currently approved or filed for approval in the USA, with the EU- and US-approved reference pegfilgrastims. Headache and bone pain were common to biosimilars and reference products and occurred at a similar incidence. Clinical trial data on the safety profiles of biosimilar pegfilgrastims and reference products have demonstrated similarity and comparability, with no unexpected safety outcomes. Overall, the safety profiles of biosimilar pegfilgrastims and reference pegfilgrastims demonstrated a high degree of similarity and comparability.
: Somatic genomic testing is recommended by numerous expert guidelines to inform targeted therapy treatment for patients with advanced nonsquamous non–small cell lung cancer (aNSCLC). The NILE study ...was a prospective observational study that demonstrated noninferiority of cell-free circulating tumor DNA (cfDNA)-based tumor genotyping compared to tissue-based genotyping to find targetable genomic alterations in patients with newly diagnosed nonsquamous aNSCLC. As the cohort has matured, clinical outcomes data can now be analyzed.
: This prospective, multicenter North American study enrolled patients with previously untreated nonsquamous aNSCLC who had standard of care (SOC) tissue genotyping performed and concurrent comprehensive cfDNA analysis (Guardant360). Patients with targetable genomic alterations, as defined by NCCN guidelines, who were treated with physician's choice of therapy had objective response rates, disease control rate, and time to treatment collected and compared to published outcomes.
: Among 282 patients, 89 (31.6%) had an actionable biomarker, as defined by NCCN, detected by tissue (21.3%) and/or cfDNA (27.3%) analysis. Sixty-one (68.5%) of these were treated with an FDA-approved targeted therapy guided by somatic genotyping results (EGFR, ALK, ROS1). Thirty-three patients were eligible for clinical response evaluation and demonstrated an objective response rate of 58% and disease control rate of 94%. Twenty-five (76%) and 17 (52%) achieved a durable response > 6 months and 12 months, respectively. The time to treatment (TtT) was significantly faster for cfDNA-informed biomarker detection as compared to tissue genotyping (18 vs. 31 days, respectively; P = .0008).
cfDNA detects guideline-recommended biomarkers at a rate similar to tissue genotyping, and therapeutic outcomes based on plasma-based comprehensive genomic profiling are comparable to published targeted therapy outcomes with tissue profiling, even in community-based centers.
Challenges remain with collecting adequate tissue biopsies to successfully perform comprehensive genomic profiling to identify NCCN-recommended biomarkers to inform first-line therapy in patients with newly diagnosed, advanced NSCLC. Plasma-based genotyping (liquid biopsy) has previously demonstrated noninferiority to tissue biopsy for identifying targetable biomarkers in patients with NSCLC and achieves genotyping at a faster rate than tissue. This study analyzed clinical outcomes of 33 patients who were treated with targeted therapy in the first-line setting based on liquid biopsy results and demonstrated that patients respond to therapy at rates similar to those treated based on tissue-genotyping results, while able to initiate targeted therapy significantly faster (18 vs. 31 days, respectively). These findings support the utility of liquid biopsy at diagnosis of advanced disease to inform targeted therapy options in a fast, noninvasive manner.
Background
This randomized, double‐blinded, phase II trial evaluated the efficacy of carboplatin and pemetrexed plus either apatorsen, an antisense oligonucleotide targeting heat shock protein (Hsp) ...27 mRNA, or placebo in patients with previously untreated metastatic nonsquamous non‐small cell lung cancer (NSCLC).
Methods
Patients were randomized 1:1 to Arm A (carboplatin/pemetrexed plus apatorsen) or Arm B (carboplatin/pemetrexed plus placebo). Treatment was administered in 21‐day cycles, with restaging every two cycles, until progression or intolerable toxicity. Serum Hsp27 levels were analyzed at baseline and during treatment. The primary endpoint was progression‐free survival (PFS); secondary endpoints included overall survival (OS), objective response rate, and toxicity.
Results
The trial enrolled 155 patients (median age 66 years; 44% Eastern Cooperative Oncology Group performance status 0). Toxicities were similar in the 2 treatment arms; cytopenias, nausea, vomiting, and fatigue were the most frequent treatment‐related adverse events. Median PFS and OS were 6.0 and 10.8 months, respectively, for Arm A, and 4.9 and 11.8 months for Arm B (differences not statistically significant). Overall response rates were 27% for Arm A and 32% for Arm B. Sixteen patients (12%) had high serum levels of Hsp27 at baseline. In this small group, patients who received apatorsen had median PFS of 10.8 months, and those who received placebo had median PFS 4.8 months.
Conclusion
The addition of apatorsen to carboplatin and pemetrexed was well tolerated but did not improve outcomes in patients with metastatic nonsquamous NSCLC cancer in the first‐line setting.
Implications for Practice
This randomized, double‐blinded, phase II trial evaluated the efficacy of carboplatin and pemetrexed plus either apatorsen, an antisense oligonucleotide targeting heat shock protein 27 mRNA, or placebo in patients with previously untreated metastatic nonsquamous non‐small cell lung cancer (NSCLC). The addition of apatorsen to carboplatin and pemetrexed was well tolerated but did not improve outcomes in patients with metastatic nonsquamous NSCLC cancer in the first‐line setting.
摘要
背景。本次随机双盲 II 期试验对卡铂和培美曲塞联合 Apatorsen一种反义寡核苷酸靶向热休克蛋白 (Hsp) 27 mRNA或安慰剂治疗既往未经治疗的非鳞状非小细胞肺癌 (NSCLC) 患者的疗效进行评估。
方法。按照 1:1 的比例将患者随机分配至 A 组(卡铂/培美曲塞联合 Apatorsen)或 B 组(卡铂/培美曲塞联合安慰剂)。治疗以 21 天为一个周期进行，每两个周期重新安排治疗，直至患者出现疾病进展或无法忍受的毒性。在基线和治疗期间对血清 Hsp27 水平进行分析。主要终点为无进展生存期 (PFS)；次要终点包括总生存期 (OS)、客观缓解率和毒性。
结果。试验招募了 155 名患者(中位年龄为 66 岁；44% 的患者的美国东部肿瘤协作组体力状态得分为 0)。2 个治疗组中的毒性相似；血细胞减少、恶心、呕吐和疲劳是最常见的治疗相关不良反应。A 组的中位 PFS 和 OS 分别为 6.0 个月和 10.8 个月，B 组的中位 PFS 和 OS 分别为 4.9 个月和 11.8 个月(差异无统计学意义)。A 组和 B 组的总缓解率分别为 27% 和 32%。在基线时，十六名患者 (12%) 的血清 Hsp27 水平较高。在这个小群体中，使用 Apatorsen 的患者的中位 PFS 为 10.8 个月，使用安慰剂的患者的中位 PFS 为 4.8 个月。
结论。在一线治疗中，卡铂和培美曲塞联合 Apatorsen 治疗的耐受性良好，但是，不能改善转移性非鳞状 NSCLC 患者的预后。
实践意义:本次随机双盲 II 期试验对卡铂和培美曲塞联合 Apatorsen(一种反义寡核苷酸靶向热休克蛋白 27 mRNA)或安慰剂治疗既往未经治疗的转移性非鳞状非小细胞肺癌 (NSCLC) 患者的疗效进行评估。在一线治疗中，卡铂和培美曲塞联合 Apatorsen 治疗的耐受性良好，但是，不能改善转移性非鳞状 NSCLC 患者的预后。
This article evaluates the efficacy and safety of apatorsen when added to a standard carboplatin/pemetrexed regimen in the first‐line treatment of patients with metastatic non‐squamous non‐small cell lung cancer.
Highlights • Use of proteomic testing modified the treatment recommendations by physicians. • Clinical outcomes were projected over lifetime based on a randomized controlled trial. • Costs for ...testing, treatment, surveillance, and AE management were assessed. • Including proteomic testing in management of NSCLC is a cost-effective strategy that improves survival and quality of life.
Objective: The VeriStrat
1
(VS) test is intended to help guide treatment decisions for patients with advanced non-small-cell lung cancer (NSCLC) without an EGFR-sensitizing mutation, classifying ...patients into two categories. Patients classified as VSGood have a favorable prognosis and significant clinical response to EGFR tyrosine kinase inhibitors (TKIs). Patients classified as VSPoor have a less favorable prognosis and exhibit no significant response to EGFR-TKIs. The objective of this paper is to assess the real-world impact of VS test results on physicians' treatment recommendations including referrals for best supportive care (BSC).
Methods: Between 1 January 2012 and 1 November 2016, physician respondents were asked to complete standardized questionnaires before and after receiving VS results in patients meeting criteria for the intended use of the VS test. This study evaluated three endpoints: whether physicians followed VS test results in making treatment recommendations, the extent to which tests results changed these treatment recommendations, and the patterns of care subsequent to VS testing.
Results: Of the tests ordered by 989 physicians, 2494 VS tests had completed treatment recommendation questionnaires both prior to and after testing. Prior to VS testing, physicians were considering treatment with EGFR-TKIs for 2250 patients (90%). The VS test classified 1950 patients as VSGood and 544 patients as VSPoor. For patients classified as VSPoor, physicians recommended BSC for 25% of patients and standard systemic treatments such as chemotherapies for 65% of patients. Consistent with previous publications, physicians recommended EGFR-TKI therapy for only 10% of VSPoor patients but for 89% of VSGood patients. Overall, physician's treatment recommendations were consistent with test results in 98% of cases. Availability of test results decreased ineffective treatment recommendations by 89% for VSPoor patients.
Conclusions: Among physicians ordering VS, the test significantly influenced treatment recommendations for patients with NSCLC, reducing ineffective and expensive treatment at the end of life.
Soft tissue involvement in extramedullary plasmacytoma (EMP) is an exceptionally rare occurrence within the spectrum of plasma cell neoplasms. This case report presents the unique scenario of a ...patient who developed a soft tissue mass EMP subsequent to receiving radiation therapy for a solitary bone plasmacytoma at a distinct anatomical site. The primary objective of this report is to elucidate the clinical characteristics, diagnostic complexities, and management considerations associated with this uncommon presentation. Through a comprehensive review of existing literature, we aim to provide valuable insights and expertise to healthcare providers involved in the assessment and treatment of similar cases.
Bilateral synchronous testicular tumors are a relatively uncommon occurrence, especially when they involve germ cell tumors of different histology. In this context, we present a compelling case ...report of a male patient who was diagnosed with bilateral synchronous germ cell testicular tumors, with one being a seminoma and the other a non-seminomatous germ cell tumor (NSGCT). The coexistence of two distinct histological types, seminoma and NSGCT, necessitates a comprehensive diagnostic approach to accurately identify and characterize each tumor. This underscores the importance of clinical history, physical examination, imaging techniques, and histopathological analysis to establish an appropriate diagnosis. Careful consideration must be given to factors such as tumor stage, histological subtype, and individual patient characteristics to determine the most suitable treatment strategy. Treatment options may encompass a combination of surgery, chemotherapy, and radiation therapy, tailored to each tumor's specific characteristics and the patient's overall health. By highlighting this unique case, we aim to underscore the significance of meticulous evaluation and accurate diagnosis when confronted with bilateral synchronous testicular tumors of different histology.
PDF
