Liquid biopsy mutation panel for non-small cell lung cancer: analytical validation and clinical concordance

Molecular testing for genomic variants is recommended in advanced non-small cell lung cancer (NSCLC). Standard tissue biopsy is sometimes infeasible, procedurally risky, or insufficient in tumor tissue quantity. We present the analytical validation and concordance study ofEGFRvariants using a new 17-gene liquid biopsy assay (NCT02762877). Of 144 patients enrolled with newly diagnosed or progressive stage IV nonsquamous NSCLC, 140 (97%) had liquid assay results, and 117 (81%) had bothEGFRblood and tissue results. Alterations were detected in 58% of liquid samples. Overall tissue-liquid concordance forEGFRalterations was 94.0% (95% CI 88.1%, 97.6%) with positive percent agreement of 76.7% (57.7%, 90.1%) and negative percent agreement of 100% (95.8%, 100%). Concordance forALKstructural variants was 95.7% (90.1%, 98.6%). This assay detected alterations in other therapeutically relevant genes at a rate similar to tissue analysis. These results demonstrate the analytical and clinical validity of this 17-gene assay

Genomic alterations and the incidence of brain metastases in advanced and metastatic non-small cell lung cancer: a systematic review and meta-analysis.

BackgroundBrain metastases (BM) in patients with advanced and metastatic non-small cell lung cancer (NSCLC) are linked with poor prognosis. Identifying genomic alterations associated with BM development could influence screening and determine targeted treatment. We aimed to establish prevalence and incidence in these groups, stratified by genomic alterations.Patients and methodsA PRISMA-compliant systematic review and meta-analysis was conducted (PROSPERO ID CRD42022315915). Articles published in MEDLINE, EMBASE, and Cochrane Library between January 2000-May 2022 were included. Prevalence at diagnosis, and incidence of new BM per year were obtained, including patients with EGFR, ALK, KRAS, and other alterations. Pooled incidence rates were calculated using random effects models.ResultsSixty-four unique articles were included (24,784 NSCLC patients with prevalence data from forty-five studies and 9,058 NSCLC patients with incidence data from forty studies). Pooled BM prevalence at diagnosis was 28.6% (45 studies, 95% Confidence Interval [CI] 26.1-31.0), and highest in patients that are ALK-positive (34.9%) or with RET-translocations (32.2%). With a median follow-up of 24 months, per-year incidence of new BM was 0.13 in the wild-type group (14 studies, 95% CI 0.11-0.16). Incidence was 0.16 in the EGFR group (16 studies, 95% CI 0.11-0.21), 0.17 in the ALK group (5 studies, 95% CI 0.10-0.27), 0.10 in the KRAS group (4 studies, 95% CI 0.06-0.17), 0.13 in the ROS1 group (3 studies, 95% CI 0.06-0.28), and 0.12 in the RET group (2 studies, 95% CI 0.08-0.17).ConclusionsComprehensive meta-analysis indicates a higher prevalence and incidence of BM in patients with certain targetable genomic alterations. This supports brain imaging at staging and follow-up, and the need for targeted therapies with brain penetrance

Immunotherapy-related adverse events in real-world patients with advanced non-small cell lung cancer on chemoimmunotherapy: a Spinnaker study sub-analysis

BackgroundThe Spinnaker study evaluated survival outcomes and prognostic factors in patients with advanced non-small-cell lung cancer receiving first-line chemoimmunotherapy in the real world. This sub-analysis assessed the immunotherapy-related adverse effects (irAEs) seen in this cohort, their impact on overall survival (OS) and progression-free survival (PFS), and related clinical factors.MethodsThe Spinnaker study was a retrospective multicentre observational cohort study of patients treated with first-line pembrolizumab plus platinum-based chemotherapy in six United Kingdom and one Swiss oncology centres. Data were collected on patient characteristics, survival outcomes, frequency and severity of irAEs, and peripheral immune-inflammatory blood markers, including the neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII).ResultsA total of 308 patients were included; 132 (43%) experienced any grade irAE, 100 (32%) Grade 1–2, and 49 (16%) Grade 3–4 irAEs. The median OS in patients with any grade irAES was significantly longer (17.5 months [95% CI, 13.4–21.6 months]) than those without (10.1 months [95% CI, 8.3–12.0 months]) (p<0.001), either if Grade 1–2 (p=0.003) or Grade 3–4 irAEs (p=0.042). The median PFS in patients with any grade irAEs was significantly longer (10.1 months [95% CI, 9.0–11.2 months]) than those without (6.1 months [95% CI, 5.2–7.1 months]) (p<0.001), either if Grade 1–2 (p=0.011) or Grade 3–4 irAEs (p=0.036). A higher rate of irAEs of any grade and specifically Grade 1–2 irAEs correlated with NLR <4 (p=0.013 and p=0.018), SII <1,440 (p=0.029 ad p=0.039), response to treatment (p=0.001 and p=0.034), a higher rate of treatment discontinuation (p<0.00001 and p=0.041), and the NHS-Lung prognostic classes (p=0.002 and p=0.008).ConclusionsThese results confirm survival outcome benefits in patients with irAEs and suggest a higher likelihood of Grade 1–2 irAEs in patients with lower NLR or SII values or according to the NHS-Lung score

A reciprocal feedback between the PDZ binding kinase and androgen receptor drives prostate cancer

We acknowledge support from the National Cancer Research Institute (National Institute of Health Research (NIHR) collaborative study: “Prostate Cancer: Mechanism of Progression and Treatment (PROMPT)” (grant G0500966/75466). This work was funded by a Cancer Research UK program grant (to DEN) and funding from the US Department of Defense (Prostate Cancer Research Program Transformative Impact Award, grant ID W81XWH-13- 2-0093; WDT, SMD and LAS), National Health and medical Research Council (grant ID 1083961; LAS) and PCFA/Cancer Australia/Movember (grant IDs 1012337 and 1043482; WDT and LAS). The research programs of WDT and LAS are supported by the Movember Foundation and the Prostate Cancer Foundation of Australia through the Movember Revolutionary Team Award. This work was also supported by the National Institutes of Health (NIH) grant R01CA174777 to SMD. FO was supported by a PhD project grant from Prostate Cancer UK (S10-10). LAS and MA were supported by a Young Investigator Award from the Prostate Cancer Foundation of the USA.Peer reviewe

Treatment beyond four cycles of first line Platinum and Etoposide chemotherapy in real-life patients with stage IV Small Cell Lung Cancer: a retrospective study of the Merseyside and Cheshire Cancer network

Abstract Background Dose intensity and dose density of first line Platinum and Etoposide (PE) do not influence Overall Survival (OS) of Small Cell Lung Cancer (SCLC) patients. The effect of treatment length, however, remains unclear. Current guidelines recommend treating beyond 4 cycles -up to 6-, in patients that respond to and tolerate systemic treatment. This has led to variable practice both in clinical practice and clinical research. Here we aimed at quantifying the possible clinical benefit of the extended regimen in our real-life patients treated with PE doublet. Methods Of all patients with SCLC treated in our network with non-concurrent first line PE chemotherapy between 2008 and 2015, we identified and described patients that received 4 cycles (4c) or more (&gt; 4c), and analysed patients with stage IV disease. Results Two hundred forty-one patients with stage IV had 4c and 69 had &gt; 4c. The latter were more likely to have sequential thoracic radiotherapy, which suggested a lower metastatic burden. Nevertheless, there were no statistically significant differences when comparing clinical outcomes. The median Duration of Response (DoR; time from last chemotherapy cycle to progression) was 5 months in both groups (HR 1.22; 95% CI 0.93–1.61). Median Progression Free Survival (PFS; time from diagnosis to radiological progression) was 8 months (4c) versus 9 months (&gt; 4c) (HR 0.86; 95% CI 0.66–1.13) and median OS was 11 versus 12 months (HR 0.86, 95% CI 0.66–1.14). Conclusion Our results highlight a lack of clinical benefit by extending first line PE treatment in stage IV disease, and support limiting treatment to 4 cycles until superiority of a longer regimen is identified in a randomised study. </jats:sec