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LETTER TO EDITOR
Year : 2019  |  Volume : 2  |  Issue : 2  |  Page : 249-250

Treating EGFR-positive advanced cancer lung – Did the water just get muddier?


Department of Medical Oncology, Silverline Hospital, Bhopal, Madhya Pradesh, India

Date of Web Publication20-Dec-2019

Correspondence Address:
Tarini Prasad Sahoo
Consultant Medical Oncologist, Silverline Hospital, Bhopal, Madhya Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_76_19

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How to cite this article:
Sahoo TP. Treating EGFR-positive advanced cancer lung – Did the water just get muddier?. Cancer Res Stat Treat 2019;2:249-50

How to cite this URL:
Sahoo TP. Treating EGFR-positive advanced cancer lung – Did the water just get muddier?. Cancer Res Stat Treat [serial online] 2019 [cited 2020 Apr 3];2:249-50. Available from: http://www.crstonline.com/text.asp?2019/2/2/249/273693



Significant progress has taken place in the treatment of advanced lung cancer, and with the advent of targeted therapies, the survival has tripled in the last decade. The debate about what would be the ideal first-line treatment in epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC) will only get fiercer after the overall survival (OS) data for the FLAURA study got presented at the ESMO 2019.[1] With osimertinib and dacomitinib being the only two tyrosine kinase inhibitors (TKI) showing superiority over the first-generation TKI (the latter not preferred due to its poor toxicity profile), can the combination of gefitinib with chemotherapy or a vascular endothelial growth factor inhibitor be considered an ideal first-line therapy in this subgroup?

In the review article published in the last issue of the journal,[2] the authors have put in perspective all the available options in this subgroup of patients, which in India will be 1/3rd of the total advanced NSCLC patient pool,[3] but there are few clinically relevant points which need a mention before an oncologist can decide on the therapy for such patients. Around 30%–40% of patients post-progression on first-line therapy do not receive a second line therapy; and this is an important fact that physicians have to remember, making the job of choosing the first-line agent much more relevant.

Also of note, the NE009 study from Japan (unpublished till date),[4] which has shown the highest survival, has demonstrated the PFS2 to be similar (gefitinib followed by chemotherapy compared to the combination), making the OS data more liable to scrutiny, and the post-progression treatment needs to be put in the public domain.

Let's assume that for 100 patients with EGFR-positive advanced NSCLC, approximately 30%–35% will have brain metastasis at presentation, and an additional 20% may develop brain metastasis in the next 5 years; osimertinib would be the preferred first-line choice in these patients.[5],[6] Add another 10% who would have a poor performance status without brain metastasis at presentation; again, single-agent TKI would be the preferred drug. With approximately 10%–12% having uncommon EGFR mutation, afatinib would be an option apart from chemotherapy and not the combination.

For the remaining 40%–45% of patients (not to mention the 3%–4% with exon 20 mutation), considering median OS with osimertinib of approximately 39 months and with 28% survival at 36 months, there would be very few patients who would opt for TKI and chemotherapy combination (taking into account its higher toxicity profile and nearly 1/5th of patients withdraw due to toxicity in the TMH data with the combination).[7]

As of today, the most preferred choice for mutations in exons 18, 19, and 21 will be osimertinib (give the “Best drug first” as per Dr. S.S. Ramalingam and specially when 30% may not be able to get a second-line therapy). The option of single-agent sequential TKI (afatinib followed by osimertinib) - data from the LUX lung 3/6/7 and GioTag study should also be discussed which have demonstrated an impressive median OS of 41.3 months and 45.7 months in patients with Del19-positive tumors while the 2-year survivals were 80 and 82% respectively.[8]The combination of gefitinib with chemotherapy although a valid first-line therapy will be preferred in developing countries specially where the patient has to bear most of the medical expense,[9] and osimertinib remains out of their reach.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ramalingam SS, Gray JE, Ohe Y, Cho BC, et al. LBA5_PR Osimertinib vs comparator EGFR-TKI as first-line treatment for EGFRm advanced NSCLC (FLAURA): Final overall survival analysis. Ann Oncol 2019;30 suppl_5:mdz394.076.  Back to cited text no. 1
    
2.
Rajendra A, Noronha V, Joshi A, Patil VM, Menon N, Prabhash K. Epidermal growth factor receptor-mutated non-small-cell lung cancer: A primer on contemporary management. Cancer Res Stat Treat 2019;2:36-53.  Back to cited text no. 2
  [Full text]  
3.
Noronha V, Prabhash K, Thavamani A, Chougule A, Purandare N, Joshi A, et al. EGFR mutations in Indian lung cancer patients: Clinical correlation and outcome to EGFR targeted therapy. PLoS One 2013;8:e61561.  Back to cited text no. 3
    
4.
Nakamura A, Inoue A, Morita S, Hosomi Y, Kato T, Fukuhara T, et al. Phase III study comparing gefitinib monotherapy (G) to combination therapy with gefitinib, carboplatin, and pemetrexed (GCP) for untreated patients (pts) with advanced non-small cell lung cancer (NSCLC) with EGFR mutations (NEJ009). J Clin Oncol 2018;36 Suppl 15:9005.  Back to cited text no. 4
    
5.
Chooback N, Lefresne S, Lau SC, Ho C. CNS metastases in epidermal growth factor receptor mutation-positive non-small-cell lung cancer: Impact on health resource utilization. J Oncol Pract 2018;14:e612-20.  Back to cited text no. 5
    
6.
Pandey A, Singh A, Singh S, Kumar A. Osimertinib in G719A mutated non-small cell lung cancer with leptomeningeal metastases. Cancer Res Stat Treat 2019;2:121-3.  Back to cited text no. 6
  [Full text]  
7.
Noronha V, Patil VM, JoshiA, Menon N, Chougule A, Mahajan A, et al. Gefitinib versus gefitinib plus pemetrexed and carboplatin chemotherapy in EGFR-mutated lung cancer. J Clin Oncol 2019:JCO1901154. [Epub ahead of print].  Back to cited text no. 7
    
8.
Hochmair MJ, Morabito A, Hao D, Yang CT, Soo RA, Yang JC, et al. Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer: Updated analysis of the observational GioTag study. Future Oncol 2019;15:2905-14.  Back to cited text no. 8
    
9.
Philip CC, Mathew A, John MJ. Cancer care: Challenges in the developing world. Cancer Res Stat Treat 2018;1:58-62.  Back to cited text no. 9
  [Full text]  



This article has been cited by
1 Author Reply to: Sahoo, Batra et al. and Mullapally et al.
Akhil Rajendra,Vanita Noronha,Amit Joshi,VijayMaruti Patil,Nandini Menon,Kumar Prabhash
Cancer Research, Statistics, and Treatment. 2019; 2(2): 252
[Pubmed] | [DOI]



 

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