Impact of renal function on treatment options and outcomes in advanced non-small cell lung cancer

Abstract Background Whereas there are many pharmacological interventions prescribed for patients with advanced anaplastic lymphoma kinase (ALK)- rearranged non-small cell lung cancer (NSCLC), comparative data between novel generation ALK-tyrosine kinase inhibitors (TKIs) remain scant. Here, we indirectly compared the efficacy and safety of first-line systemic therapeutic options used for the treatment of ALK-rearranged NSCLC. Methods We included all phase 2 and 3 randomised controlled trials (RCTs) comparing any two or three treatment options. Eligible studies reported at least one of the following outcomes: progression free survival (PFS), overall survival (OS), objective response rate (ORR), or adverse events of grade 3 or higher (Grade ≥ 3 AEs). Subgroup analysis was conducted according to central nervous system (CNS) metastases. Results A total of 9 RCTs consisting of 2484 patients with 8 treatment options were included in the systematic review. Our analysis showed that alectinib (300 mg and 600 mg), brigatinib, lorlatinib and ensartinib yielded the most favorable PFS. Whereas there was no significant OS or ORR difference among the ALK-TKIs. According to Bayesian ranking profiles, lorlatinib, alectinib 600 mg and alectinib 300 mg had the best PFS (63.7%), OS (35.9%) and ORR (37%), respectively. On the other hand, ceritinib showed the highest rate of severe adverse events (60%). Conclusion Our analysis indicated that alectinib and lorlatinib might be associated with the best therapeutic efficacy in first-line treatment for major population of advanced NSCLC patients with ALK-rearrangement. However, since there is little comparative evidence on the treatment options, there is need for relative trials to fully determine the best treatment options as well as the rapidly evolving treatment landscape.

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“My Patient Was Diagnosed With Nontargetable Advanced Non–Small Cell Lung Cancer. What Now?” Diagnosis and Initial Treatment Options for Newly Diagnosed Patients With Advanced NSCLC

American Society of Clinical Oncology Educational Book ◽

10.1200/edbk_201231 ◽

2018 ◽

pp. 696-707 ◽

Cited By ~ 3

Author(s):

Melissa Johnson ◽

Nathan A. Pennell ◽

Hossein Borghaei

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Treatment Options ◽

The United States ◽

Small Cell ◽

Small Cell Lung ◽

Platinum Based Chemotherapy ◽

Treatment Naïve ◽

Novel Therapeutic Strategies

Although lung cancer remains the leading cause of cancer-related mortality in the United States and worldwide, the rate at which Americans are dying from lung cancer is declining. Improving survival can be explained, in large part, by a growing understanding of the heterogeneous biology of non–small cell lung cancer (NSCLC) as well as recent successes of novel therapeutic strategies more effective and tolerable than platinum-based chemotherapy. We now recognize distinct subtypes of NSCLC, defined by molecular profiling and immunohistochemistry, with different treatment algorithms, including targeted small molecular inhibitors and immunotherapy for each. Both biomarker selection and preferred frontline strategies continue to evolve rapidly, making it difficult for many practitioners to keep up. In this review, we will first describe the recommended initial workup for a patient with advanced or metastatic NSCLC in 2018; next, we present an algorithm to aid oncologists in the selection of the most appropriate therapy for treatment-naive patients with NSCLC, and finally, we offer a look into future treatment options through a discussion of ongoing clinical trials.

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Non-Radiation Based Early Pain Relief Treatment Options for Patients With Non-Small Cell Lung Cancer and Cancer Induced Bone Pain: A Systematic Review

Frontiers in Oncology ◽

10.3389/fonc.2020.509297 ◽

2020 ◽

Vol 10 ◽

Author(s):

Anita J. W. M. Brouns ◽

Ben H. De Bie ◽

Marieke H. J. van den Beuken-van Everdingen ◽

Anne-Marie C. Dingemans ◽

Lizza E. L. Hendriks

Keyword(s):

Lung Cancer ◽

Systematic Review ◽

Pain Relief ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Bone Pain ◽

Treatment Options ◽

Small Cell ◽

Small Cell Lung

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Targeting KRAS Mutant Non-Small-Cell Lung Cancer: Past, Present and Future

International Journal of Molecular Sciences ◽

10.3390/ijms21124325 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4325 ◽

Cited By ~ 1

Author(s):

Iris Z. Uras ◽

Herwig P. Moll ◽

Emilio Casanova

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Biological Diversity ◽

Treatment Options ◽

Small Cell ◽

Small Cell Lung ◽

Advanced Stages ◽

Direct Targeting ◽

Aggressive Clinical Course

Lung cancer is the most frequent cancer with an aggressive clinical course and high mortality rates. Most cases are diagnosed at advanced stages when treatment options are limited and the efficacy of chemotherapy is poor. The disease has a complex and heterogeneous background with non-small-cell lung cancer (NSCLC) accounting for 85% of patients and lung adenocarcinoma being the most common histological subtype. Almost 30% of adenocarcinomas of the lung are driven by an activating Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation. The ability to inhibit the oncogenic KRAS has been the holy grail of cancer research and the search for inhibitors is immensely ongoing as KRAS-mutated tumors are among the most aggressive and refractory to treatment. Therapeutic strategies tailored for KRAS+ NSCLC rely on the blockage of KRAS functional output, cellular dependencies, metabolic features, KRAS membrane associations, direct targeting of KRAS and immunotherapy. In this review, we provide an update on the most recent advances in anti-KRAS therapy for lung tumors with mechanistic insights into biological diversity and potential clinical implications.

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PDGFR-β expression in small cell lung cancer patients

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.17128 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 17128-17128

Author(s):

B. Lu

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Prognostic Value ◽

Treatment Options ◽

Cell Cancer ◽

Small Cell ◽

Tumor Control ◽

Small Cell Lung ◽

Significant Difference

17128 Background: Small cell lung cancer (SCLC) carries an extremely poor prognosis and treatment options for this disease remain poor. PDGF and PDGFR-β are expressed and have been found to have prognostic value in several human cancers. Data in non-small cell cancer cell lines have suggested that PDGFR is a therapeutic target for drug development. In the current study PDGFR-β expression and prognostic value in SCLC was investigated. Methods: Paraffin embedded tissue blocks from 53 patients with limited and extensive stage SCLC were obtained for immunohistochemical staining. Tumors from each patient were sampled three times and stained with PDGFR-β specific antibody. Patients were divided into low and high staining groups based on intensity. Results: There was high intensity PDGFR-β staining in 20 patients with SCLC. Another 29 expressed low intensity PDGFR- β staining, with only 4 patients showing no PDGFR- β staining. There was no statistically significant difference in five year overall survival between patients with low levels of PDGFR-β staining versus those with high level staining SCLC tumors (P = 0.538). Conclusions: Though expression of PDGFR-β may not be a predictor of prognosis, due to its high expression in SCLC it may represent an important target for improved tumor control, however, further studies are required to confirm this. No significant financial relationships to disclose.

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Genetic landscape and PD-L1 expression of Chinese patients with small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21099 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21099-e21099

Author(s):

Meifang Chen ◽

Ding Zhang ◽

Guoqiang Wang ◽

Bijiong Wang

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Treatment Options ◽

Small Cell ◽

Chinese Patients ◽

Genomic Profiling ◽

Small Cell Lung ◽

Genetic Landscape ◽

Expression Status

e21099 Background: Small cell lung cancer (SCLC) is a highly aggressive carcinoma of the lung. Whereas, precise treatment options for SCLC are limited. Genomic profiling would be essential to understand drug resistance related mechanism. So far, little is known about an in-depth molecular characterization for SCLC in Chinese patients. Here we described the mutational landscape and programmed cell death-1 (PD-L1) expression profile in Chinese patients with SCLC by next-generation sequencing (NGS) assay. Methods: Chinese patients with SCLC were included in this study. Genomic profiling of DNA was performed on formalin-fixed paraffin-embedded tumor samples and matched blood through a NGS with 381 cancer-related genes panel. PD-L1 expression status of tumor tissue was determined by immunohistochemistry. Results: In total, 115 patients with SCLC were included in the present study. We identified 2,948 mutations, spanning 434 genes, with TP53, RB1 and LRP1B being the most frequently mutated genes, occurring in 109(94.78%), 88(76.52%) and 48(41.74%) of SCLC patients, respectively. For somatic single nucleotide variant (SNV), TP53 (108/115, 93.91%), RB1 (82/115, 71.30%) and LRP1B (43/115, 37.39%) were frequently mutated, which exhibited the similar mutation frequencies with TCGA database. To be noted, 79 (68.70%) SCLC patients harbored both RB1 and TP53 mutations, which was comparable with TCGA data (84/110, 76.36%). Germline SNV spectrum varied significantly compare with somatic SNV. BLM, MSH2 and VEGFA were the most frequently germline mutated genes. In our dataset, the tumor mutation burden (TMB) of 108 patients, PD-L1 expression status of 95 patients and microsatellite stabilities/instabilities (MSS/MSI) status of 112 patients were also analyzed. The median TMB was 10.61/MB. The positive rate of PD-L1 expression was 12.63%. All patients were MSS. Conclusions: Our study revealed the genetic landscape and PD-L1 expression of SCLC. The data may provide the support on immunotherapy and targeted therapy research.

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