Lung cancer third line therapy

Following the results of the CROWN phase III trial, the third-generation macrocyclic ALK inhibitor lorlatinib has been introduced as a salvage option after the failure of a first-line TKI in ALK-rearranged NSCLC, while its precise role in the therapeutic algorithm of ROS1 positive disease is still to be completely defined. The ability to overcome acquired resistance to prior generation TKIs (alectinib, brigatinib, ceritinib, and crizotinib) and the high intracranial activity in brain metastatic disease thanks to increased blood-brain barrier penetration are the reasons for the growing popularity and interest in this molecule...

BACKGROUND: Lorlatinib is a brain-penetrant, third-generation anaplastic lymphoma kinase (ALK) inhibitor indicated for ALK-positive metastatic non-small cell lung cancer (NSCLC). In a global phase II study, patients who experience disease progression despite prior treatment with ALK tyrosine kinase inhibitors (TKIs) was assessed. Herein, we report real-world clinical outcomes of lorlatinib-treated patients with ALK-positive advanced NSCLC who were heavily pretreated and progressed on first- and second-generation ALK-TKIs, in a Taiwanese population under the lorlatinib expanded access program (EAP)...

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) as the most common type. In addition, NSCLC has a high mortality rate and an overall adverse patient outcome. Although significant improvements have been made in therapeutic options, effectiveness is still limited in late stages, so the need for a better understanding of the genomics events underlying the current therapies is crucial to aid future drug development. Vinorelbine (VRB) is an anti-mitotic chemotherapy drug (third-generation vinca alkaloid) used to treat several malignancies, including NSCLC...

BACKGROUND: This case report addresses the dearth of effective therapeutic interventions for central nervous system metastases in patients with HER2-negative breast cancer. It presents a unique case of a woman with estrogen receptor-positive, HER2-negative breast cancer who developed brain metastasis. The report highlights her initial favorable response to abemaciclib and letrozole therapy prior to the discontinuation due to drug-induced lung damage (DILD). CASE SUMMARY: In this comprehensive case summary, we present the clinical course of a woman in her 60s, who 11 years following primary breast cancer surgery, was diagnosed with multiple brain metastases...

BACKGROUND: The clinical efficacy and safety of camrelizumab as a third- or later-line regimen in patients with advanced non-small cell lung cancer (NSCLC) have not been determined in large clinical trials. OBJECTIVE: This study aimed to evaluate the clinical efficacy and safety of camrelizumab in combination with albumin-bound paclitaxel as a third- or later-line treatment for patients with advanced NSCLC. METHODS: A total of 257 patients with advanced NSCLC who were histopathologically confirmed and failed in clinical second-line therapy regimens at Jiangxi Province Cancer hospital from January 2018 to December 2021 were retrospectively selected...

BACKGROUND: Immune checkpoint inhibitors (ICIs) have changed the therapeutic options for extensive-stage small-cell lung cancer (ES-SCLC). In this real-world study, we analyzed the treatment patterns in patients with ES-SCLC and evaluated the efficacy of chemotherapy combined with immunotherapy as first-line therapy. METHODS: A retrospective analysis was performed on patients with ES-SCLC who received treatment at China-Japan Friendship Hospital (Beijing, China) between August 1, 2020, and April 30, 2023...

In the past 15 years, non-small cell lung cancer (NSCLC) treatment has changed with the discovery of mutations and the development of new targeted therapies and immune checkpoint inhibitors. Epidermal growth factor receptor ( EGFR ) was the first mutation in NSCLC to have a drug that was FDA-approved in 2013. Osimertinib, a third-generation tyrosine kinase inhibitor, is approved as first-line therapy for advanced NSCLC and in the adjuvant setting for Stage IB-IIIA resected NSCLC. However, resistance to osimertinib is inevitably an issue, and thus patterns of resistance to EGFR -mutated NSCLC have been studied, including MET amplification, EGFR C797X-acquired mutation, human epidermal growth factor 2 (HER2) amplification, and transformation to small cell and squamous cell lung cancer...

Immune checkpoint inhibitor (ICI)-induced myocarditis is one of the most serious and potentially fatal toxicities of immunotherapy. Most of the guidelines for managing this toxicity are based on expert opinions. Human epidermal growth factor receptor 2 (HER2) alterations in non-small cell lung cancer (NSCLC) could be found using next-generation sequencing (NGS) on tissue and liquid biopsies. There is an approved first-line targeted therapy for HER2-positive breast and gastroesophageal cancers. Until now, no first-line targeted therapy for NSCLC with HER2 alterations has been approved...

BACKGROUND: Anaplastic lymphoma kinase ( ALK ) rearrangement confers sensitivity to second- and third-generation ALK inhibitors, which have become the standard of care for ALK-positive non-small cell lung carcinoma (NSCLC). However, primary resistance to these inhibitors remains a rare and poorly understood phenomenon, especially in cases involving kinesin light chain 1 ( KLC1 )/ ALK -rearranged metastatic NSCLC. CASE DESCRIPTION: In this report, we present a unique and challenging case of primary resistance to second- and third-generation ALK tyrosine kinase inhibitors (TKIs) attributed to KLC1/ALK gene fusion partners in a patient with ALK-positive pleural metastatic NSCLC...

BACKGROUND: Epidermal growth factor receptor ( EGFR ) exon 20 insertion (ex20ins) mutation is the third most common EGFR -mutant form, accounting for 10-12% of all EGFR mutations in non-small cell lung cancer (NSCLC). Chemotherapy was the first-line treatment for patients with EGFR ex20ins mutation in the era when EGFR ex20ins tyrosine kinase inhibitors ( EGFR ex20ins-TKIs) were inaccessible. Although EGFR ex20ins-TKIs have since then demonstrated certain efficacy, the population benefit rate is not high due to the high cost of the drug and limited benefit to the population...

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the current recommended option for the first-line treatment of patients with EGFR-mutant non-small cell lung cancer (NSCLC). Resistance to first-generation TKIs led to the development of second- and third-generation TKIs with improved clinical outcomes. However, sequential administration of TKIs has led to the emergence of new EGFR resistance mutations and persistent tumor cell survival. This evidence highlights the potential role of EGFR in transducing growth signals in NSCLC tumor cells...

OBJECTIVE: This study aims to investigate and analyze the correlation between EGFR-TKI first-line therapy and EGFR mutation status in patients with advanced lung cancer. METHODS: We selected 60 patients with advanced lung cancer and EGFR mutations (diagnosed as stage IIIb or IV) from our hospital between January 2019 and November 2022. Each patient underwent an EGFR mutation test and was categorized into two groups based on their mutation status: 28 patients with exon 21 mutations and 32 with exon 19 deletions...

AIMS: SCLC is the most aggressive lung cancer histology with a 5-year OS <10%. At the diagnosis, almost two-thirds of the SCLC an Extended Disease presentation. Two randomized studies (CASPIAN and ImPower133) demonstrated an OS improvement, when immunotherapy was prescribed as maintenance therapy after standard chemotherapy. To date, SABR has had a limited indication in managing metastatic SCLC, although recent reports proposed it as a valid treatment option in selected patients. We propose a retrospective multicentric analysis of patients treated with SABR for oligometastatic SCLC...

INTRODUCTION: Necitumumab plus gemcitabine and cisplatin (GCN) is a standard therapy for patients with advanced lung squamous cell carcinoma (LSqCC). However, the efficacy and tolerability of GCN in second-line or later treatment for patients previously treated with immune checkpoint inhibitors (ICIs) remain unknown. METHODS: This multicenter, retrospective, cohort study assessed the efficacy and tolerability of GCN initiated between November 1, 2019 and March 31, 2022 as second-line to fourth-line treatment in patients with advanced LSqCC who had been pretreated with ICIs...

Background: The treatment paradigm for advanced non-small-cell lung cancer (NSCLC) is rapidly changing. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and anti-programmed death-1 (PD-1) antibodies have increasingly been incorporated into routine care for nearly all patients with NSCLC. Toripalimab was recently approved as the first-line treatment for advanced non-squamous NSCLC in combination with chemotherapy. Stevens-Johnson syndrome (SJS) is a rare but potentially fatal complication of TKI and anti-PD-1 therapy...

Anti-angiogenesis therapy plays a vital role in the treatment of tumors, with anlotinib as its representative targeted drug. Anlotinib is a novel oral tyrosine kinase inhibitor (TKI) with inhibitory effects on tumor growth tumor angiogenesis. In Phase III clinical trials, anlotinib demonstrated better overall survival and progression-free survival than placebo in patients with advanced non-small cell lung cancer (NSCLC), and was approved for the first time as a third-line treatment for refractory advanced NSCLC...

We report the case of a 68-year-old man who developed a sigmoidorectal fistula after marked response to enfortumab vedotin for advanced bladder cancer. The patient had undergone radical cystectomy with ileal conduit after neoadjuvant chemotherapy. Six months after surgery, local recurrence in the pelvic cavity and multiple lung metastases were found, and the patient was administered pembrolizumab as second-line therapy. Due to worsening local recurrence and suspected invasion of the sigmoid colon and rectum, enfortumab vedotin was initiated as third-line therapy and comprehensive genomic profiling was simultaneously performed...

Radionecrosis describes a rare but serious complication of radiation therapy. In clinical practice, stereotactic radiosurgery (SRS) is increasingly used in combination with systemic therapy, including chemotherapy, immune checkpoint inhibitor and targeted therapy, either concurrently or sequentially. There is a paucity of literature regarding radionecrosis in patients receiving whole brain radiation therapy (WBRT) alone (without additional SRS) in combination with immunotherapy or targeted therapies. It is observed that certain combinations increase the overall radiosensitivity of the tumorous lesions...

BACKGROUND: Although ALK-translocated (ALK+) advanced non-small cell lung cancers (aNSCLCs) are currently treated with second- or third-generation ALK inhibitors (ALK-TKIs), some patients respond durably to the first-generation ALK-TKI crizotinib. OBJECTIVE: This study aimed to describe the clinical characteristics of these long-term responders. PATIENTS AND METHODS: This national, multicenter, retrospective, non-interventional study included patients with ALK+ aNSCLCs and long-term responses to first (L1)- or subsequent (≥ L2)-line crizotinib, defined, respectively, as treatments lasting > 18 and > 10 months...

Lung cancer is one of the most common malignant tumors with the highest incidence. Gene mutations are rare in small-cell lung carcinoma (SCLC), resulting in targeted therapy being only a third-line recommendation. Surufatinib (Sulanda) is an oral angio-immune kinase inhibitor used to treat solid tumors. We report a case of SCLC treated with surufatinib combined with camrelizumab, with good therapeutic results in our department. The patient experienced over 18 months of progression-free survival and over 28 months of overall survival...