Anti-ALK autoantibodies in patients with ALK-positive Non-Small Cell Lung Cancer (NSCLC): A monocentric experience.

Importance: Deregulation of anaplastic lymphoma kinase (ALK) occurs in 3-7% of advanced NSCLC mainly because of chromosomic rearrangements at the ALK locus. Next to its oncogenic function, ALK chimeric oncoprotein is a possible antigen for human immune system. The prognostic value of natural anti-ALK immunogenicity remains poorly explored in ALK ​+ ​NSCLC.

Antecedent viral immunization and efficacy of immune checkpoint blockade: an extensive serum antibody profile to predict outcomes in non-small cell lung cancer.

Introduction: Immune checkpoint blockers (ICBs) revolutionized the treatment of patients with advanced non-small cell lung cancer (NSCLC) but only a fraction of them obtain a response, and clinical benefit from these treatments is often difficult to predict. The aim of our study is to unveil the potential implications of antibody response to previous viral infections in predicting response to ICBs in patients with NSCLC.

Methods: Sera from patients treated with ICBs alone, chemotherapy (CT) or a combination of CT-ICBs were analyzed with VirScan (CDI Labs, USA), a high-throughput method that comprehensively analyzes epitope-level antiviral IgG antibodies via programmable phage display and immunoprecipitation sequencing.

Liquid Biopsy versus CT: Comparison of Tumor Burden Quantification in 1065 Patients with Metastases.

Background Tumor fraction (TF) at liquid biopsy is a potential noninvasive marker for tumor burden, but validation is needed. Purpose To evaluate TF as a potential surrogate for tumor burden, assessed at contrast-enhanced CT across diverse metastatic cancers. Methods This retrospective monocentric study included patients with cancer and metastatic disease, with TF results and contemporaneous contrast-enhanced CT performed between January 2021 and January 2023.

Neoadjuvant immunotherapy strategies for resectable non-small cell lung cancer (NSCLC): Current evidence among special populations and future perspectives.

About one third of patients with Non-Small Cell Lung Cancer (NSCLC) presents at diagnosis with localized or locally advanced disease amenable to curative surgical resection. Surgical operability refers to stage I to IIIA and selected stage IIIB NSCLC. One of the main challenges in the management of early-stage resectable NSCLC is the optimization of available therapeutic strategies to prevent local and distant disease relapse, thus improving survival outcomes.

Real-World Outcomes of First-Line Treatment With Anti-PD(L)1-Based Combination Therapy for Nonsquamous Metastatic Non-Small Cell Lung Cancer: A Multiregional Chart Review in Europe, Japan, and the United States.

Purpose: Anti-PD-1/PD(L)1-based combination therapy is the standard of care in first line (1L) for metastatic nonsquamous non-small cell lung cancer (mnsqNSCLC) without driver alterations. This study aimed to evaluate real-world clinical outcomes in this population.

Methods: Eligible physicians in the United States, Europe, and Japan abstracted information from medical charts of eligible adult patients with mnsqNSCLC (without /, no known alterations) who initiated 1L anti-PD(L)1-based combination therapy for mnsqNSCLC between 2017 and 2021.

Efficacy and safety of bintrafusp alfa in 2 phase I expansion cohorts with advanced HCC.

Background And Aims: Simultaneous inhibition of the TGF-β and programmed cell death 1 ligand 1 pathways provides a potential novel treatment approach. Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-βRII (a TGF-β "trap") fused to a human IgG1 monoclonal antibody blocking programmed cell death 1 ligand 1, was evaluated in patients with advanced HCC.

Approach And Results: In this global, open-label, phase I study (NCT02517398), patients with programmed cell death 1 ligand 1-unselected HCC who failed or were intolerant to ≥1 line of sorafenib received bintrafusp alfa 1200 mg every 2 weeks in a dose-escalation (n = 38) or dose-expansion (n = 68) cohort until confirmed progression, unacceptable toxicity, or trial withdrawal.

Impact of pembrolizumab treatment duration on overall survival and prognostic factors in advanced non-small cell lung cancer: a nationwide retrospective cohort study.

Background: The efficacy of front-line pembrolizumab has been established in studies that limit treatment duration to 2 years, but decision to stop pembrolizumab after 2 years is often at physician's discretion. ATHENA is a retrospective cohort study using a comprehensive administrative database aimed firstly at exploring the optimal duration of pembrolizumab and secondly real-life prognosis factors in patients with advanced non-small cell lung cancer (NSCLC).

Methods: Using the French National Health Insurance database (SNDS), we identified patients with incident lung cancer in France from 2015 to 2022.

PACIFIC-9: Phase III trial of durvalumab + oleclumab or monalizumab in unresectable stage III non-small-cell lung cancer.

Evidence from the Phase III PACIFIC trial established durvalumab, a monoclonal antibody (mAb) targeting PD-L1, following concurrent chemoradiotherapy (cCRT) as a global standard of care for patients with unresectable, stage III non-small-cell lung cancer (NSCLC). There remains an unmet need to improve upon the outcomes achieved with the PACIFIC regimen. Combining durvalumab with other immunotherapies may improve outcomes further.

Capmatinib plus nazartinib in patients with EGFR-mutated non-small cell lung cancer.

Purpose: This phase 1b/2 trial evaluated the efficacy and safety of capmatinib plus nazartinib in patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC).

Methods: In phase 1b, patients with progression on first-/second-generation EGFR-TKIs received escalating doses of capmatinib 200-400 mg bid plus nazartinib 50-150 mg qd. Once the MTD/RP2D was declared, phase 2 commenced with patient enrollment into groups according to mutation status and prior lines of treatment: group 1 (fasted; EGFR-TKI resistant; 1-3 prior lines; EGFR; any T790M/MET); group 2 (fasted; EGFR-TKI naïve; 0-2 prior lines; de novo T790M+; any MET); group 3 (fasted; treatment-naïve; EGFR; T790M-; any MET); group 4 (with food; 0-2 prior lines; EGFR; any T790M/MET).

Cancer Core Europe: Leveraging Institutional Synergies to Advance Oncology Research and Care Globally.

Cancer Core Europe brings together the expertise, resources, and interests of seven leading cancer institutes committed to leveraging collective innovation and collaboration in precision oncology. Through targeted efforts addressing key medical challenges in cancer and partnerships with multiple stakeholders, the consortium seeks to advance cancer research and enhance equitable patient care.

Recommendations for the use of next-generation sequencing (NGS) for patients with advanced cancer in 2024: a report from the ESMO Precision Medicine Working Group.

Background: Advancements in the field of precision medicine have prompted the European Society for Medical Oncology (ESMO) Precision Medicine Working Group to update the recommendations for the use of tumour next-generation sequencing (NGS) for patients with advanced cancers in routine practice.

Methods: The group discussed the clinical impact of tumour NGS in guiding treatment decision using the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) considering cost-effectiveness and accessibility.

Results: As for 2020 recommendations, ESMO recommends running tumour NGS in advanced non-squamous non-small-cell lung cancer, prostate cancer, colorectal cancer, cholangiocarcinoma, and ovarian cancer.

Reactions and adverse events induced by T-cell engagers as anti-cancer immunotherapies, a comprehensive review.

T-cell engagers (TCE) are cancer immunotherapies that have recently demonstrated meaningful benefit for patients with hematological malignancies and solid tumors. The anticipated widespread use of T cell engagers poses implementation challenges and highlights the need for guidance to anticipate, mitigate, and manage adverse events. By mobilizing T-cells directly at the contact of tumor cells, TCE mount an obligatory and immediate anti-tumor immune response that could result in diverse reactions and adverse events.

Toxicity of immunotherapy combinations with chemotherapy across tumor indications: Current knowledge and practical recommendations.

Chemotherapy associated with Immune Checkpoint Inhibitors is currently the standard of care in several tumor indications. This combination approach improves progression free survival (PFS), overall survival (OS) and complete pathological response (pCR) in several cancer types both in the early and metastatic approaches. However, the distinct spectrum of toxicities between cytotoxic side effects and immune related adverse events (irAEs) with similar clinical presentations and different management strategies remains a challenge in daily practice for healthcare professionals.

Immune checkpoint blockers in solid organ transplant recipients and cancer: the INNOVATED cohort.

Background: Patients with solid organ transplant (SOT) and solid tumors are usually excluded from clinical trials testing immune checkpoint blockers (ICB). As transplant rates are increasing, we aimed to evaluate ICB outcomes in this population, with a special focus on lung cancer.

Methods: We conducted a multicenter retrospective cohort study collecting real data of ICB use in patients with SOT and solid tumors.

Alectinib in Resected -Positive Non-Small-Cell Lung Cancer.

Background: Platinum-based chemotherapy is the recommended adjuvant treatment for patients with resectable, -positive non-small-cell lung cancer (NSCLC). Data on the efficacy and safety of adjuvant alectinib as compared with chemotherapy in patients with resected -positive NSCLC are lacking.

Methods: We conducted a global, phase 3, open-label, randomized trial in which patients with completely resected, -positive NSCLC of stage IB (tumors ≥4 cm), II, or IIIA (as classified according to the seventh edition of the of the American Joint Committee on Cancer and Union for International Cancer Control) were randomly assigned in a 1:1 ratio to receive oral alectinib (600 mg twice daily) for 24 months or intravenous platinum-based chemotherapy in four 21-day cycles.

Long-Term Outcomes After Concurrent Once- or Twice-Daily Chemoradiation in Limited-Stage Small Cell Lung Cancer: A Brief Report From the CONVERT Trial.

Purpose: CONVERT was a phase 3 international randomized clinical trial comparing once-daily (OD) and twice-daily (BD) radiation therapy (RT). This updated analysis describes the 6.5-year outcomes of these regimens delivered with conformal techniques.

Overcoming immuno-resistance by rescheduling anti-VEGF/cytotoxics/anti-PD-1 combination in lung cancer model.

Many tumors are refractory to immune checkpoint inhibitors, but their combination with cytotoxics is expected to improve sensitivity. Understanding how and when cytotoxics best re-stimulate tumor immunity could help overcome resistance to immune checkpoint inhibitors. studies were performed in C57BL/6 mice grafted with immune-refractory LL/2 lung cancer model.