We aimed to evaluate the efficacy and safety of granulocyte-colony stimulating factor (G-CSF) prophylaxis during chemoimmunotherapy with carboplatin plus etoposide and atezolizumab in extensive-stage small cell lung cancer (ES-SCLC). This retrospective, multicenter study enrolled ES-SCLC patients receiving carboplatin plus etoposide and atezolizumab, categorized into G-CSF and non-G-CSF groups. Demographic and disease-related data were collected. Response rates, progression-free survival (PFS), overall survival (OS), and toxicity were analyzed. Of 119 patients (median age: 63 years), the overall response rate (ORR) and disease control rate (DCR) were 72.3% and 81.5%, respectively. In the G-CSF group, the ORR was 76.4% compared to 60.0% in the non-G-CSF group (p = 0.33), and the DCR was 85.4% versus 70.0%, respectively (p = 0.46). Median PFS was 8.3 months (95% CI, 6.8-9.8) in the G-CSF group and 6.8 months (95% CI, 6.2-7.5) in the non-G-CSF group (p = 0.24). Median OS was 13.8 months (95% CI, 9.6-18.1) for the G-CSF group and 10.6 months (95% CI, 7.9-13.3) for the non-G-CSF group (p = 0.47). Grade 3 ≥ adverse events were similar between groups (49.4% vs. 33.3%, respectively, p = 0.12). G-CSF prophylaxis can be safely used in ES-SCLC patients undergoing carboplatin plus etoposide and atezolizumab regimen without significantly altering efficacy or increasing toxicity.
11 June 2024 in Journal of Oncology Pharmacy Practice
Objective: The objective of this article is to review the efficacy, safety, and evidence for current use and potential future uses of immune-checkpoint inhibitors (ICIs) in the management of resectable non-small cell lung cancer (NSCLC). Data sources: A literature review was carried out through PubMed to identify completed and ongoing clinical trials evaluating the use, efficacy, and safety of ICIs in the management of resectable NSCLC. Data summary: To date, four phase 3 trials have emerged that have changed our treatment practice concerning the utilization of ICIs during the adjuvant and neoadjuvant settings. The IMpower010 and KEYNOTE-091 trials examined the application of adjuvant atezolizumab and pembrolizumab, respectively, following surgical resection and adjuvant chemotherapy. In the CheckMate 816 trial, the combination of nivolumab and chemotherapy as a neoadjuvant therapy received approval for patients with resectable NSCLC. Also, for patients with resectable NSCLC, the use of a pembrolizumab and chemotherapy combination as a perioperative therapy received approval based on the results of the KEYNOTE-671 trial. Apart from these trials, there are numerous phase 2 and phase 3 trials, some of which have been published while others are still in progress. Conclusion: Despite the promising outcomes from these trials there remain several unanswered questions. In this review, we will assess clinical trials involving adjuvant, neoadjuvant, and perioperative ICIs, aiming to address the unresolved questions related to these therapeutic approaches.
Background: Lung cancer remains the leading cause of cancer-related deaths worldwide, with non-small cell lung carcinomas (NSCLCs) comprising the majority of cases. Among the common driver mutations, KRAS plays a critical role in guiding treatment strategies. This study evaluates the expression of programmed death-ligand 1 (PD-L1) and hypoxia-inducible factor 1-alpha (HIF-1α) in KRAS-mutant NSCLCs and investigates their associations with clinicopathological findings. Methods: A total of 85 cases with KRAS mutations were analyzed. Immunohistochemical staining for HIF-1α and PD-L1 was performed, and their relationships with mutation status and prognostic variables were assessed. Results: A significant correlation was identified between HIF-1α expression and PD-L1 expression in tumor cells. While the KRAS G12C mutation was not significantly associated with HIF-1α expression in tumor cells, it demonstrated a notable relationship with HIF-1α expression in the tumor microenvironment and PD-L1 expression. However, PD-L1 and HIF-1α expression did not significantly influence overall survival outcomes. Conclusions: Expression of PD-L1 was positively correlated with HIF-1α, which may provide evidence for a novel therapy targeting PD-L1 and HIF-1α in NSCLC. Further comprehensive studies are warranted to elucidate the prognostic implications of tumor–microenvironment and mutation interactions.
Background: Although CDK4/6 inhibitors combined with endocrine therapies have improved outcomes in HR+ HER2-negative metastatic breast cancer, predictive biomarkers for treatment response and adverse effects remain limited. This study assessed the prognostic and predictive value of large unstained cells (LUC), a subset of white blood cells that may reflect immune status or treatment response. Methods: A retrospective analysis of 210 patients with HR+ HER2-negative metastatic breast cancer treated with CDK 4/6 inhibitors between 2021 and 2024 was conducted. Clinical data, including demographics, tumor characteristics, and treatment regimens, were analyzed. Based on LUC levels, progression-free survival (PFS), overall survival (OS), and adverse events were evaluated. Results: The cohort had a median age of 57, of which 78% were postmenopausal. Common metastatic sites included bone (67%) and liver (24%). At a median follow-up of 18.5 months, the PFS and OS rates were 65% and 83%. Patients with low LUC levels had significantly shorter PFS (OR: 1.91; p = 0.014) and OS (OR: 2.39; p = 0.012), while high LUC levels correlated with a lower incidence of grade 3 neutropenia (OR: 0.49; p = 0.017). Liver metastasis and prior treatments were also linked to shorter survival. Conclusions: LUC levels emerge as a promising biomarker for predicting survival outcomes and the risk of neutropenia in HR+ HER2-negative metastatic breast cancer patients treated with CDK 4/6 inhibitors and endocrine therapy, showing their potential to guide personalized treatment approaches.