ALK rearrangement

Our study adds to the evidence regarding the role of the grading system in prognosis. EGFR, KRAS, and ALK are related to the degree of tumor differentiation.

For NSCLC with ALK, RET and ROS1 rearrangement, MET exon 14 skipping mutation, or BRAF V600E mutation, effectiveness of single or combined ICI therapy remains limited, therefore, targeted therapies should be considered prior to immunotherapy regimens. Future studies should address the investigation of better predictive biomarkers for immunotherapy response in oncogene-driven NSCLC.

The patient whose tumor harbored SEC31A::PDGFRA was treated after multiple relapses with imatinib and sunitinib therapy, with progression-free periods of 5 and 2 years, respectively. Despite its bland appearance, myxoid inflammatory myofibroblastic sarcoma harbors a significant risk for disseminated disease, particularly when it occurs in the peritoneum. Targeted therapy could be considered for patients with disseminated disease.

P1, N=24, Active, not recruiting, Jonsson Comprehensive Cancer Center | Recruiting --> Active, not recruiting | Trial completion date: Jun 2025 --> Jan 2025 | Trial primary completion date: Jun 2024 --> Jan 2024

P2 | N=33 | Active, not recruiting | Sponsor: Fundación GECP | Trial primary completion date: Apr 2024 ➔ Dec 2024

To date, more new agents and regimens can achieve satisfactory results in patients with NSCLC. In this review, we focus on recent advances and highlight the new approval of molecular targeted therapy for NSCLC patients with rare oncologic drivers.

P2, N=143, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | N=101 --> 143

P2, N=114, Active, not recruiting, Assistance Publique Hopitaux De Marseille | Recruiting --> Active, not recruiting | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Oct 2023 --> Oct 2024

ALK-rearranged Spitz tumour confirmed with FISH analysis favour clinically benign behaviour despite atypical histomorphology or positive sentinel lymph node. Therefore, correlation of histomorphology, immunohistochemical stain and molecular study are important for the definitive diagnosis of this entity.

P4, N=50, Recruiting, Novartis Pharmaceuticals | Trial completion date: Jul 2024 --> Jun 2025 | Trial primary completion date: Jul 2024 --> Jun 2025

No abstract available

Crizotinib, a first-generation ALK inhibitor, was approved in the USA in 2021 for pediatric patients and young adults with relapsed or refractory ALK-positive ALCL; however, its safety and efficacy have not been established in older adults...This podcast provides an overview of ALK-positive ALCL and IMT. We discuss the current treatment landscape, the role of ALK tyrosine kinase inhibitors, and areas of future research.

No abstract available

Both PNI and mGPS can be used as a reliable, inexpensive, and easily applicable prognostic index in the advanced lung cancer patients who had the targetable mutation and also received targeted therapy.

P1, N=18, Completed, Elpiscience Biopharma, Ltd. | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Mar 2024

Furthermore, a patient with an ALK-rearranged tumor achieved a remarkable 3-year progression-free survival following crizotinib treatment. Overall, our findings deepen the understanding of the complex genomic landscape of PSCC, revealing actionable targets amenable to tailored treatment of this poorly characterized malignancy.

The patient responded well with no evidence of residual or recurrent disease on follow-up imaging or surveillance esophagogastroduodenoscopy. Crizotinib was ultimately discontinued after 10 months of therapy, and the patient continues to undergo surveillance imaging for monitoring of disease burden.

P1/2, N=16, Active, not recruiting, Massachusetts General Hospital | Recruiting --> Active, not recruiting | N=31 --> 16 | Trial completion date: Nov 2024 --> Jan 2027 | Trial primary completion date: Nov 2022 --> Jan 2025

P1/2, N=12, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting --> Recruiting

We discuss the role of NGS as well as its potential benefit in patients with unresectable, ALK-negative metastatic disease. Considering this case and previous literature, we support the use of NGS for patients requiring systemic treatment.

The NGS testing revealed EML4::ALK fusion in three, STRN::ALK fusion in two, and ITSN2::ALK fusion in one. In conclusion, although ALK-rearranged PTCs have been associated with neutral gene expression profile from a BRAF-RAS scoring perspective, the "RAS-like" nuclear features were more commonly identified in this series, resulting in frequent indeterminate diagnosis of preoperative FNA.

Based on literature review and our experience in this case report, we concluded that crizotinib-associated renal cyst (CARCs) has features of malignancy and abscess in radiographic imaging, and thus, pathological confirmation is necessary to avoid inappropriate treatment decision. In addition, to benefit the patients with progress-free survival (PFS), switching from crizotinib to alectinib is recommended for the treatment of NSCLC patients who developed CARCs.

Our expert opinion encapsulates the critical importance of understanding resistance mechanisms in the context of ALK inhibitors for shaping successful treatment approaches. With a focus on molecular testing and comprehensive assessment, this review contributes valuable insights to the evolving landscape of NSCLC therapy.

Additionally, this review discusses practical diagnostic considerations including overlap between uterine IMT and smooth muscle tumours as well as pregnancy-associated uterine IMT. Finally, we highlight recent literature demonstrating the potential for aggressive behaviour in uterine IMT, including a novel risk stratification model for identifying high-risk IMT.

Several anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have been developed for the treatment of echinoderm microtubule-associated protein-like 4 (EML4)-ALK-rearranged non-small cell lung cancer (NSCLC), with the newer generation agents brigatinib, alectinib and lorlatinib showing prolonged responses. The second ALK resistance mutation detected after a chemotherapy interval, the G1202R, is the most common resistance mutation after second generation ALK TKIs and has been associated with sensitivity to third generation TKIs, such as lorlatinib. This case of a patient with EML4-ALK-rearranged NSCLC shows that sequential treatment with next-generation ALK TKIs, including rechallenge, can induce profound remissions, even in heavily pretreated patients, and that ALK-targeted strategies may be personalized by considering the presence of distinct ALK resistance mutations.

A significantly higher proportion of ATCs expressed p53 and PD-L1, and a lower proportion expressed PAX-8 and TTF-1, than the coexisting DTCs. Our findings provide more reliable evidence that ATCs and PDTCs are derived from DTCs.

No abstract available

Three cases previously classified as PTCL CD30+CD15+ showed DUSP22/IRF4 rearrangements, favouring a diagnosis of ALCL, ALK-. Our results suggest that cases previously designated PTCL CD30+CD15+, likely fall within the spectrum of ALCL, ALK-; additionally, a subset of ALCL, ALK- with DUSP22/IRF4 rearrangement expresses CD15, consistent with previous reports and expands the immunophenotypic spectrum of this lymphoma subgroup.

P2, N=117, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2024 --> Sep 2024 | Trial primary completion date: Jun 2024 --> Sep 2024

Therefore, based on the reported status of immunotherapy combined with chemotherapy for advanced NSCLC, this study conducted a comprehensive literature review by searching keywords "PD-1 and PD-L1, immune checkpoint inhibitor (ICI), and NSCLC" in MEDLINE, major conferences, and major clinical research projects to elucidate the therapeutic efficacy of immunotherapy combined with chemotherapy as the current first-line treatment approach for various types of NSCLC patients. Additionally, it addresses several pressing challenges associated with immunotherapy combined with chemotherapy, including enhancing treatment response and survival rate in specific patient populations and identifying potential biomarkers.

P1/2, N=470, Recruiting, Nuvalent Inc. | N=320 --> 470

A study presented in the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago emphasized the need for comprehensive genomic profiling (CGP) before single gene tests (SGTs) since it demonstrated that SGT can result in the depletion of precious biopsy samples. As a result, the efficacy of thorough genetic Profiling (CGP) is reduced, preventing patients from receiving valuable genetic information about their tumors.

To enhance the outcome of these patients, we need to understand the mechanisms of acquired resistance and evaluate the role of new drugs with novel mechanisms of action in the treatment landscape. In this chapter, we review treatment strategies of EGFR-mutant tumors in all stages, the mechanisms of acquired strategies, and novel therapies in this subset.

P1, N=5, Active, not recruiting, City of Hope Medical Center | Recruiting --> Active, not recruiting | N=31 --> 5

For advanced lung adenocarcinomas, with no targetable driver mutations, there is evidence-based guidance on the use of carboplatin-paclitaxel chemotherapy after first trimester. In contrast, for epidermal growth factor receptor (EGFR)-mutated or anaplastic lymphoma kinase (ALK)-rearranged metastatic lung adenocarcinomas, there is a paucity of clinical data on the safety of EGFR and ALK tyrosine kinase inhibitors to mother and fetus for official guidelines to recommend the use of these otherwise-first-line therapies in pregnancy. Considering this knowledge gap, we present a case of a young gravida 1 para 0 (G1P0) woman who continued alectinib 300 mg oral two times per day for ALK-rearranged metastatic lung adenocarcinoma throughout all 36 weeks of her pregnancy and delivered a healthy baby at term via caesarean section (C-section).

Both patients were treated with surgical resection and reconstruction. The prognosis of patients with this entity is currently uncertain but shall become more apparent over time as more cases are identified and followed.

P1, N=40, Recruiting, NYU Langone Health | Phase classification: P1/2 --> P1

P2, N=5, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Feb 2025

Already, important management aspects are apparent for several of these entities, while emerging therapeutic angles are coming into view. A brief, clinically-oriented introduction of the entities in this new category, focusing on relevant diagnostic, molecular, and management aspects, is the subject of this review.

P1/2, N=49, Active, not recruiting, Takeda | Recruiting --> Active, not recruiting | N=231 --> 49

No abstract available

P2, N=373, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed