Cancer Research, Statistics, and Treatment

: 2019  |  Volume : 2  |  Issue : 2  |  Page : 251--252

First-line treatment of EGFR-mutant NSCLC: Spoiled for choice?

Ullas Batra, Mansi Sharma, Srujana Joga, Parveen Jain 
 Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India

Correspondence Address:
Ullas Batra
Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Rohini, Sector 5, New Delhi - 110 085

How to cite this article:
Batra U, Sharma M, Joga S, Jain P. First-line treatment of EGFR-mutant NSCLC: Spoiled for choice?.Cancer Res Stat Treat 2019;2:251-252

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Batra U, Sharma M, Joga S, Jain P. First-line treatment of EGFR-mutant NSCLC: Spoiled for choice?. Cancer Res Stat Treat [serial online] 2019 [cited 2021 Aug 5 ];2:251-252
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Full Text

Lung cancer is the poster child for personalized medicine. In the last decade, the treatment of lung cancer has undergone a paradigm shift with the development of biomarkers such as epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase rearrangement. The treatment of EGFR-mutant non-small cell lung cancer (NSCLC) itself has undergone a major change with various treatment options available for first-line treatment.[1]

Various factors should be taken into account while choosing the first-line treatment for EGFR-mutant NSCLC. These include efficacy, toxicity, quality of life, and cost–benefit analysis. The results of IRESSA Pan-Asia Study and EURopean TArceva vs. Chemotherapy trials established gefitinib/erlotinib as the first-line treatment of EGFR-mutant NSCLC. However, patients invariably progress after 9–12 months. Various strategies have been used to increase the progression-free survival (PFS)/overall survival (OS) including the combination of EGFR tyrosine kinase inhibitors (TKIs) with chemotherapy, combination with anti-angiogenics, and use of third-generation TKIs.

The results of AZD9291 Versus Gefitinib or Erlotinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (FLAURA) trial established osimertinib as the standard of care in the first-line treatment of this subgroup of patients. Osimertinib not only prolongs the PFS,[2] but also results in improved OS.[3] The drug is also very well tolerated[4] and has the added advantage of penetrating the blood–brain barrier. Nearly 26% of the patients who received the drug are still continuing the drug at 3 years.[5]

It should also be noted that 30% of patients in both the arms of the FLAURA trial could not take second-line treatment.[5] In addition, only 50% of the patients would develop T790M mutation while on progression on the first-/second-generation TKIs.[6],[7] Thus, a majority of eligible patients may not be able to take osimertinib if not used in the first-line setting.

The other strategies used to increase the PFS are a combination of EGFR with anti-angiogenic agents and EGFR chemotherapy combinations. The results of EGFR chemotherapy combinations are promising, but this regimen is associated with higher toxicity and high rates of discontinuation of treatment. The OS data of Tata Memorial Hospital trial are not yet mature,[8] and the results of the NEJ009 trial have not yet been published.[9] The addition of anti-angiogenics to EGFR TKIs has similarly yielded an improvement in PFS but is again associated with higher rates of toxicity in the combination arm.[10]

Osimertinib is the only TKI that has shown OS advantage in head-to-head comparison with another TKI. Even in the Alectinib with Crizotinib in Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer trial (ALEX), alectinib has not shown OS advantage till date.[11] Even in other cancers such as chronic myeloid leukemia and gastrointestinal stromal tumor, later-generation TKIs have not been able to show increased OS advantage compared to first-generation TKIs. Thus, in view of overall OS, improved central nervous system penetration rates,[12] and better toxicity profile, osimertinib should be considered as the standard of care first-line treatment of EGFR-mutant NSCLC in 2019.

However, the last word on the combination of chemotherapy and EGFR TKIs has not yet been delivered. The FLAURA 2 trial, which is a Phase III clinical trial comparing osimertinib to a combination of osimertinib/pemetrexed and cisplatin, is currently recruiting patients. The results of this trial should provide a clear answer to the optimal first-line management of EGFR-mutant NSCLC.

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Conflicts of interest

There are no conflicts of interest.


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