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Published on: February 12, 2017
Customized chemotherapy in metastatic non-small cell lung cancer (NSCLC)
Jia Wei1, Teresa Moran2, Zhengyun Zou1
1Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, China ;
Abstract:
Metastatic non-small cell lung cancer (NSCLC) unfortunately remains a lethal disease, despite recent genetic characterization of subclasses of NSCLC, mainly adenocarcinoma, which has led to the development of targeted therapies that improve progression-free survival (PFS). Ultimately, however, patients fatally relapse. In this review we will focus on the search to improve survival for NSCLC patients deemed to be pan-negative for the common driver alterations susceptible to targeted therapy, above all those with EGFR mutations or ALK, ROS or RET translocations. Other uncommon driver mutations such as HER2 and BRAF mutations should be tested in order to rule out targeted treatment before assigning patients to chemotherapy. Chemotherapy yields short lived response with median survival still less than one year. Customized chemotherapy represents one way to attempt to prolong survival, although to date no prospective randomized customized studies have reported sufficient evidence to support this. In one attempt to demonstrate the role of tailoring chemotherapy, the Spanish Lung Cancer Group (SLCG) phase II customized chemotherapy trial (NCT00883480) showed that RAP80, a component of the BRCA1-A complex, influenced outcome in patients with low BRCA1 expression treated with cisplatin/gemcitabine, and in patients with intermediate/high BRCA1 levels receiving cisplatin/docetaxel or docetaxel alone. We are currently performing a prospective, randomized phase III trial comparing non-customized cisplatin/docetaxel with customized therapy in metastatic NSCLC patients (NCT00617656/GECP-BREC) and a parallel phase II study (ChiCTR-TRC-12001860) is being carried out in China (BREC-China) under the auspices of the SLCG.
Insights
This review explores improving survival for metastatic non-small cell lung cancer (NSCLC) patients lacking common targets. Customized chemotherapy, guided by biomarkers like BRCA1 expression, shows promise in prolonging survival beyond standard treatments.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Metastatic non-small cell lung cancer (NSCLC) remains a significant cause of cancer mortality.
- While targeted therapies have improved progression-free survival (PFS) for specific NSCLC subtypes, many patients eventually relapse.
- Patients negative for common driver alterations (e.g., EGFR, ALK, ROS, RET) often receive chemotherapy with limited efficacy.
Purpose of the Study:
- To review strategies for improving survival in metastatic NSCLC patients lacking common actionable mutations.
- To discuss the role of genetic profiling, including uncommon mutations (HER2, BRAF), in guiding treatment decisions.
- To evaluate the potential of customized chemotherapy approaches in this patient population.
Main Methods:
- Review of current literature and clinical trials focusing on NSCLC treatment strategies.
- Analysis of genetic alterations and their impact on therapeutic response.
- Discussion of ongoing and completed clinical trials investigating customized chemotherapy (e.g., SLCG trials NCT00883480, NCT00617656, ChiCTR-TRC-12001860).
Main Results:
- Chemotherapy alone provides short-lived responses with median survival under one year for pan-negative NSCLC.
- A Phase II trial (NCT00883480) suggested that RAP80 expression influences outcomes with specific chemotherapy regimens based on BRCA1 levels.
- Ongoing Phase III trials are comparing customized versus non-customized chemotherapy in metastatic NSCLC.
Conclusions:
- Identifying and testing for uncommon driver mutations is crucial before defaulting to chemotherapy.
- Customized chemotherapy, potentially guided by biomarkers like BRCA1 expression, offers a promising avenue for improving survival in NSCLC patients.
- Further research and prospective randomized trials are essential to establish the efficacy of tailored chemotherapy regimens.
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