PD-L1 mutation

The characterization of metastatic tumour samples can improve response prediction to immunotherapy, the anti-NECTIN4 antibody-drug conjugate enfortumab vedotin and the FGFR inhibitor erdafitinib. Routine metastatic biopsy can thus improve the precision of identifying driver druggable alterations, thus improving treatment selection for patients with mUC.

Here we summarize the current understanding of the molecular pathogenesis of ATLL, focusing on recent progress made by genetic, epigenetic, and single-cell analyses. These findings not only provide a deeper understanding of the molecular pathobiology of ATLL, but also have significant implications for diagnostic and therapeutic strategies.

Our results show guttiferone E to be a promising, novel and potent antitumor drug candidate for osimertinib-resistant lung cancer with EGFR L858R/T790M mutations.

This review highlights the need for further research to elucidate the exact mechanisms of ICI-associated pancreatic injury, develop predictive biomarkers, and refine treatment protocols. As ICI use continues to expand, a thorough understanding of this adverse event is essential for optimizing patient care and outcomes in cancer immunotherapy.

Although a rare occurrence and known to have a poor prognosis, B-Raf mutation positive programmed death ligand 1 overexpressed lung adenocarcinoma presenting with metastatic musculoskeletal lesions can respond favorably to a combination immune checkpoint inhibitor and BRAF inhibitor medication.

She underwent endoscopy and imaging; she also received transfusions, IVIG and pulse dexamethasone given concerns for ITP...Patient was initiated on carboplatin/pemetrexed (pembrolizumab held given refractory ITP)... A concurrent case of lung adenocarcinoma with IPT-like FDCS is unusual. We would like to highlight this rare entity especially in the setting of severe thrombocytopenia and the clinical challenges in using PD-1 inhibitors (such as pembrolizumab) which are known to cause thrombocytopenia.

The LAR subtype was characterized by a high rate of PIK3CA mutation, CD274 (encodes PD-L1) and PDCD1LG2 (encodes PD-L2) deletion, and a low homologous recombination deficiency (HRD) score. The non-LAR LD TIL group was characterized by a high frequency of NOTCH2 and MYC amplification and a high HRD score.

Seventeen patients received immunotherapy, and 1 patient received targeted therapy with the MET inhibitor glumetinib. PSC has a higher incidence in the elderly, smokers, and males, is highly malignant and has a poor prognosis. Based on its molecular biological characteristics, PD-L1 expression and tumor molecular detection can be performed to guide treatment options.

Taken together, these results confirm the value of biomarker testing in ES-NSCLC. Although approved targeted therapies for ES-NSCLC are still limited, the identification of actionable alterations could improve patients' selection for immunotherapy, favoring the enrollment in clinical trials and allowing a faster treatment start at disease recurrence.

Our findings contribute to the growing evidence that PD-L1 is expressed in the majority of invasive VSCCs, and thus may serve as an attractive therapeutic target. PD-L1 expression is higher in HPV-independent tumors, suggesting that this subtype may be more responsive to PD-L1 inhibitor therapy.

PFS was longer than expected with both regimens. A patient subset with wild-type BRCA platinum-sensitive aTNBC had durable disease control with chemotherapy-free maintenance.

Moreover, giving MSI-H tumors are often diagnosed at early stage and have favorable outcomes, less aggressive treatment strategies may be considered in clinical practice. In summary, this panoramic review may assist in design and/or interpretation of clinical trials, provide references in drug development, and constitute complementary information in drafting the clinical practice guideline.

Patients with low sTILs had a significantly worse overall survival (multivariate: HR 2.80; 95% CI 1.36-5.78; p = .02). Patients with low sTILs had a significantly poorer survival, despite adequate treatment with adjuvant therapy.

Using CRISPR-Cas9 genome editing, we generated biallelic PD-L1 mutants in human induced pluripotent stem cells (hiPSCs). The PD-L1 homozygous-knockout hiPSCs retained their normal morphology, gene expression, and in vivo differentiation potential.

Better overall survival and progression-free survival were observed in high PD-L1 expression tumors, regardless of KRAS mutation type. The heterogeneous nature of KRAS-mutant tumors and the presence of other co-mutations may contribute to different outcomes to immunotherapy-based strategies.

Conversely, pharmacological ACLY inhibition impedes aberrant AP-1 signaling in PD-1-deficient T-NHLs and is toxic to these cancers. Our data uncover genotype-specific vulnerabilities in PDCD1-mutated T-NHL and identify PD-1 as regulator of AP-1 activity.

P=N/A, N=29, Terminated, Muhammad Furqan | N=100 --> 29 | Active, not recruiting --> Terminated; low enrollment and remaining oncologist workload

Here, we report a case that continuous pembrolizumab monotherapy treatment induced complete remission of a recurrent cervical cancer patient with systemic metastasis and PIK3CA-E545K mutation, implying that PIK3CA mutation is potentially a biomarker for pembrolizumab treatment in cervical cancer...PIK3CA mutations may predict the response of cervical cancer to PD-1 blockade. The efficacy of PI3Kα inhibitors combined with PD-1 antibodies is promising in cervical cancer and warrants additional clinical and mechanistic investigations.

Conclusions F1CDx and TSO500 showed robust analytical performance for TMB assessment with TSO500 showing stronger concordance of TMB with high PD-L1 expression. As paradigm for early-resected NSCLC continues to evolve, understanding TMB and mutation landscape may help advance clinical outcomes for this subset of patients.

No abstract available

The three most used first-line chemotherapy treatments were Paclitaxel+Carboplatin (47.4%), Pemetrexed + Carboplatin (16.4%), and Gefitinib (5.06%). A higher smoking index and asbestos by year in the squamous histology vs non squamous one was found, most common treatment received as first line were chemotherapy, this is the first study in Mexico addressing clinical and treatment patterns in early lung cancer.

We identify the predictive utility of EGFR mutation and PD-L1 ≥50% status on local control in NSCLC patients with spinal metastases treated with spine SBRT, and a therapeutic benefit with peri-SBRT IO.

Sotorasib and adagrasib are targeted drugs that have been proven effective and approved for KRAS G12C mutation, but they have not yet entered the Chinese market. Conclusions Bringing immunotherapy to first-line use in NSCLC patients with KRAS mutation might prolong their survival, and combination therapy is a preferable option compared to monotherapy. Positive PD-L1 expression and common KRAS mutations may serve as potential prognostic biomarkers for KRAS-mutated NSCLC patients who receive immunotherapy.

Patients with resectable LA-NSCLC and an EGFR driver mutation treated with neoadjuvant-ChRT and completion surgery have reduced pathologic regression, lower local control rates, and shorter disease-free survival than patients without a driver mutation. Evaluation of molecular testing should be introduced in LA-NSCLC intended for prognostication and treatment decisions.

Possible future (bio-)markers, such as PD-L1, mutations, circulating tumor DNA (ctDNA) or Positron emission tomography (PET) need to be evaluated further in a prospective setting. In conclusion, we propose that the concept of discontinuing ICI therapy in patients with tumor response has to be seriously taken into consideration as it may be of benefit to our patients and health care systems.

Real-world survival data indicates poor prognosis in patients with locoregional recurrence. There is a need for new diagnostic tools to detect molecular recurrence through minimal residual disease (MRD) monitoring, enabling earlier and potentially more efficacious treatment for NSCLC.

PD-1/PD-L1 levels are significantly higher in MM patients and could be a promising biomarker for the disease. Variants of PD-L1 and PD-1 are linked to serum-soluble proteins and are associated with the development of MM.

We identify the predictive utility of EGFR mutation and PD-L1 =50% status on local control in NSCLC patients with spinal metastases treated with spine SBRT, and a therapeutic benefit with peri-SBRT IO.

The patient began carboplatin/pemetrexed as first line chemotherapy and was treated concurrently for latent TB due to IGRA positivity. Most recently, she started targeted immunotherapy against HER2 with trastuzumab-deruxtecan and is pending follow up imaging to evaluate progression... It is important to recognize that miliary nodules may be a presentation of malignancies rather than the classical association with tuberculosis. A positive IGRA and miliary pattern on CXR should prompt expedited workup to exclude miliary metastatic disease and miliary tuberculosis given widespread prevalence in the adult population worldwide.

Lung cancer cases diagnosed through LDCT were more likely to be at earlier stages, adenocarcinoma histology, and have a current smoking history compared to cases diagnosed outside of the screening program. There was no significant difference in LC specific biomarkers between the two cohorts. These findings highlight the importance of early detection through LCS programs, while also suggesting a need for larger studies to validate if biomarkers are similar between the two populations.

Seventeen (65.3%) subjects got one of EGFR-TKI therapy gefitinib, erlotinib or afatinib. Most EGFR mutated NSCLC patients were adenocarcinoma histologic subtype, metastatic stage, had point mutation exon 21 and deletion exon 19. Most subjects were not progressive with EGFR-TKIs targeted therapy.

Seventeen (41.5%) subjects got Platinum based chemotherapy and eighteen (43.9%) subjects got anti EGFR therapy erlotinib or gefitinib. The clinical features of NSCLC were male sex, non-smokers, mostly elderly, adenocarcinoma pathology, and diagnosed at advanced metastatic stage. Most subjects had EGFR mutation and underwent anti-EGFR treatment. The evaluation after the first 6 months, mostly were in favorable response.

Here, we report a case that continuous pembrolizumab monotherapy treatment induced a complete remission of a recurrent cervical cancer patient with systemic metastasis and PIK3CA-E545K mutation, implying that PIK3CA mutation is potentially a biomarker for pembrolizumab treatment in cervical cancer...PI3Kα-specific inhibitors markedly activate immune microenvironment by regulating the PD-1/L1-related pathways and promotes CD8+ T cell differentiation, proliferation in Caski-CDXs with PIK3CA-E545K mutation. PI3Kα inhibitor significantly enhances the anti-tumor efficacy of PD-1 blockade in CDXs and PDXs.Conclusion The efficacy of PI3K inhibitors combined with PD-1 antibodies is promising in cervical cancer and warrants additional clinical investigations.

P=N/A, N=100, Active, not recruiting, Muhammad Furqan | Recruiting --> Active, not recruiting | Trial completion date: Apr 2023 --> Aug 2023 | Trial primary completion date: Apr 2023 --> Aug 2023

Findings obtained in this study may help to determine treatment options according to the clinical condition of the patient by using LIPI values as a non-invasive, readily available and economically acceptable predictive biomarker in lung oncology.; Public health; Endoscopy and interventional pulmonology; Cell and molecular biology; General respiratory patient care; Respiratory intensive care; Epidemiology; Surgery

Better KPS score, female, and lung adenocarcinoma were independently associated with better PFS. Conclusion The results of this study suggest that SRS for patients with >10 BM may be non-inferior in OS to patients with 2–10 BM.

FGFR alteration frequency varied between the different stages of cancer. Higher positivity rates were observed at early stages, but lower levels of PD-L1 expression were detected in patients with FGFR mutations across at all stages of the disease.

For patients with multiple tumors, inter-tumoral heterogeneity of PD-L1 expression is common. Several actionable gene mutations were found to be more commonly occurred in PD-L1-heterogenous tumors. Physicians should carefully consider PD-L1 and genomic assessments by case in order to select appropriate patients for ICI treatments.

To our knowledge, this is the first study of this scale to correlate PD-L1 expression, somatic mutation data, histologic features, and survival in mesothelioma patients. The most significant findings were that patients with CDKN2A mutations had shorter survival and TP53 mutations, which were more prevalent in pleural mesotheliomas, were associated with higher nuclear grade, higher mitotic count, and greater nuclear atypia. An ongoing analysis evaluates the contribution of germline mutations, which occurred in a significant proportion (15.7%) of this mesothelioma patient cohort.

To begin with a brief on cancer immunology in general and in NSCLC, in particular, is discussed. In the end, recent advancements in laboratory techniques for refining biomarker assays are described.

Response rates to traditional immunotherapies are low and novel approaches such as the bifunctional fusion protein Bintrafusp alfa (BA) that concurrently blocks PD-L1 signaling and neutralizes TGFβ are actively under investigation...We assessed immune responses to BA in wild-type mice bearing established mouse oral cancer (MOC)-1 tumors that were randomized into the following groups: 1) vehicle; 2) anti-PD-L1 antibody (Avelumab); 3) TGFβ neutralizing construct with a mutated PD-L1 antibody (BA-M); 4) TGFβ neutralizing construct with a functional PD-L1 antibody (BA)...Although TGFβ neutralization alone fails to induce anti-tumor immunity, the addition of TGFβ neutralization to PD-L1 blockade provides greater control of primary tumor growth and protection from engraftment of a challenge tumor compared to PD-L1 blockade alone. Through adoptive transfer of tumor-specific T cell receptor-engineered T cells, ongoing experiments aim to determine if TGFβ-driven CD103 expression is required for T cell tumor residency and if neutralization of TGFβ in the setting of PD-L1 immune checkpoint blockade allows for recirculation of tumor-specific T cells into the periphery.

The Panel produced a set of prioritized considerations/consensus statements reflecting the Panel position on diagnostic and staging approach, first-line and second-line treatments of PD-L1-positive/germline BRCA (gBRCA) wild-type, PD-L1-positive/gBRCA mutated, PD-L1-negative/gBRCA wild-type and PD-L1-negative/gBRCA mutated TN mBC. The Panel critically and comprehensively discussed the most relevant and/or unexpected results and put forward possible interpretations for statements not reaching the consensus threshold.