|LETTER TO EDITOR
|Year : 2019 | Volume
| Issue : 2 | Page : 249-250
Treating EGFR-positive advanced cancer lung – Did the water just get muddier?
Tarini Prasad Sahoo
Department of Medical Oncology, Silverline Hospital, Bhopal, Madhya Pradesh, India
|Date of Web Publication||20-Dec-2019|
Tarini Prasad Sahoo
Consultant Medical Oncologist, Silverline Hospital, Bhopal, Madhya Pradesh
Source of Support: None, Conflict of Interest: None
|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
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. 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, 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, 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Also of note, the NE009 study from Japan (unpublished till date), which has shown the highest survival, has demonstrated the PFS2 to be similar (gefitinib followed by chemotherapy compared to the combination),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., 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).
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.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, and osimertinib remains out of their reach.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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