Influence of first-line chemotherapy and EGFR mutations on second-line gefitinib in advanced non-small cell lung cancer

PURPOSE: Since the increased use of first-line chemotherapy for non–small-cell lung cancer (NSCLC), second-line chemotherapy may nowadays be considered for a growing group of patients. Guidelines for second-line treatment have to be developed yet. METHODS: We reviewed the published literature on second-line chemotherapy for NSCLC with emphasis on the role of factors such as pretreatment, response to first-line treatment, and length of disease-free-interval. RESULTS: Thirty-four single-agent-studies and 24 multidrug-studies on second-line treatment were identified. Docetaxel has been studied most extensively and is the only agent that has been studied in randomized phase III trials. Different definitions of sensitivity applied by different authors and conflicting results have been reported about the influence of response to prior chemotherapy. CONCLUSION: Since most patients are treated with a platinum-based regimen in the first line, platinum resistance usually is a major consideration for the use of second-line agents. We argue, however, that a more general definition of drug resistance is more appropriate than resistance to platinum only. Criteria to select NSCLC patients for second-line treatment have not been defined yet. This is also important in light of the upcoming necessity to test new drugs in pretreated instead of treated patients. Guidelines for second-line treatment of NSCLC based on clinical information on drug sensitivity to first-line therapy need to be developed.

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Albumin-bound paclitaxel plus PD-1/PD-L1 inhibitor versus second-line chemotherapy for patients with recurrent small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e20591 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e20591-e20591

Author(s):

Fengchun Mu ◽

Bingjie Fan ◽

Butuo Li ◽

Wenru Qin ◽

Xinyu Fan ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Objective Response ◽

Small Cell ◽

Second Line ◽

Small Cell Lung ◽

First Line ◽

Second Line Chemotherapy ◽

Line Chemotherapy

e20591 Background: The main aim of this study was to evaluate the efficiency of albumin-bound paclitaxel (nab-PTX) plus PD-1/PD-L1 inhibitor versus second-line chemotherapy in small cell lung cancer (SCLC) patients who have failure to the first-line standard treatment. Methods: We retrospectively collected patients’ data from medical records between January 2015 to July 2020 in Shandong Cancer Hospital and Institute. Consecutive 42 patients who were treated with nab-PTX plus PD-1/PD-L1 inhibitor were enrolled and compared with, 126 patients who received second-line chemotherapy (1:3 matched with patient and tumor characteristics). Progress free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) were evaluated for each group. Results: Patients treated with nab-PTX plus immunotherapy group and second-line chemotherapy group achieved the median PFS of 5.6 months and 3.3 months ( p = 0.043), respectively. The median OS were 7.7 months and 6.3 months ( p = 0.021), respectively. The ORR and DCR were also higher in nab-PTX plus PD-1/PD-L1 inhibitor group (ORR: 33.3% vs 20.6%, p = 0.094; DCR: 61.9% vs 41.3%, p = 0.020, respectively). The most common incidences of grade ≥3 adverse events were leukopenia and neutropenia, there were no significance difference between the two groups. Conclusions: Albumin-bound paclitaxel plus PD-1/PD-L1 inhibitor conferred higher ORR and DCR, and improved PFS and OS in SCLC patients failed with first-line treatment. Further prospective and randomized trial that directly compares the treatments is urgently warranted.

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BIM deletion polymorphism to predict systemic treatment outcome in advanced non-small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.8055 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 8055-8055

Author(s):

Jih-hsiang Lee ◽

Yu-lin Lin ◽

Hsuan-Yu Chen ◽

Yeun-Chung Chang ◽

Chong-Jen Yu ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Second Line ◽

Small Cell Lung ◽

First Line ◽

Deletion Polymorphism ◽

Nsclc Patients ◽

Line Chemotherapy

8055 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) and chemotherapies are treatments for EGFR mutant non-small cell lung cancer (NSCLC) patients. We explored the predictive factors for progression-free survival (PFS) and overall survival (OS) on first-line EGFR-TKIs and second-line chemotherapies in NSCLC patients. Methods: One hundred and six chemonaïve NSCLC patients who received first line gefitinib in a phase II study were prospectively followed until death. Clinical and molecular biomakers were correlated with PFS and OS. Results: The OS and PFS of first-line gefitinib treatment were 19.4 (95% CI 15.6-23.3) months and 7.4 (95% CI 6.7-8.1) months, respectively. Sixty-nine patients (65%) received subsequent second-line chemotherapy. Median PFS and OS of second-line chemotherapy were 5.7 (95% CI 4.8-6.6) and 15.1 (95% CI 10.5-20.2) months. Bcl-2-like protein 11 (also named as BIM) deletion polymorphism was found in 17 out of 101 (16.8%) patients tested. The median PFS from first-line gefitinib in patients carrying normal BIM and deletion polymorphism were 8.1 months and 3.6 months, respectively (p<0.001), and the median OS were 22.1 months and 14.1 months, respectively (p=0.041); in 44 patients with common EGFR mutations (del 19 or L858R), the PFS for patients carrying normal BIM and deletion polymorphism were 9.6 months and 7.4 months, respectively (p=0.034). A multivariate analysis suggested that BIM deletion polymorphism and EGFR mutational status were independent predictors for gefitinib PFS (hazard ratio 2.83, p=0.001, and 0.63, p=0.03, respectively). Conclusions: BIM deletion polymorphism predicts shorter PFS in EGFR mutation NSCLC patients treated with first line gefitinib.

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Chemo-immunotherapy as first-line treatment for small-cell lung cancer

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920980365 ◽

2020 ◽

Vol 12 ◽

pp. 175883592098036

Author(s):

Saira Farid ◽

Stephen V. Liu

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Predictive Biomarkers ◽

High Response Rate ◽

Small Cell ◽

Standards Of Care ◽

Small Cell Lung ◽

First Line ◽

Line Chemotherapy

Small-cell lung cancer (SCLC) is a highly lethal subtype of lung cancer. Despite concerted efforts over the past several decades, there have been limited therapeutic advances. Traditional chemotherapy offers a high response rate and rapid symptomatic improvement, but its benefit is fleeting, and relapse is quick and unforgiving. Immunotherapy has delivered improved outcomes for patients with many cancers and there was compelling rationale for development in SCLC. While initial efforts with cytotoxic T-lymphocyte protein-4 inhibitors failed to improve upon chemotherapy alone, the addition of programmed death ligand-1 (PD-L1) inhibitors to first-line chemotherapy finally provided long-awaited gains in survival. Atezolizumab, when added to carboplatin and etoposide, improved both progression-free survival and overall survival. Durvalumab, when added to platinum plus etoposide, similarly improved OS. Biomarker development has stalled as PD-L1 expression and tumor mutational burden have not been useful predictive biomarkers. However, based on the significant survival improvements, both atezolizumab and durvalumab were approved by the US Food and Drug Administration to be given with first-line chemotherapy, and these regimens represent the new standards of care for SCLC.

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