|LETTERS TO EDITOR
|Year : 2021 | Volume
| Issue : 1 | Page : 187-188
Authors' reply to Devakumar et al., Katte et al., and Batra et al.
Suresh Kumar Bondili, Vanita Noronha, Anuradha Chougule, Kumar Prabhash
Department of Medical Oncology, Mumbai, Maharashtra, India
|Date of Submission||03-Mar-2021|
|Date of Decision||04-Mar-2021|
|Date of Acceptance||06-Mar-2021|
|Date of Web Publication||26-Mar-2021|
Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai - 400 012, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Bondili SK, Noronha V, Chougule A, Prabhash K. Authors' reply to Devakumar et al., Katte et al., and Batra et al.. Cancer Res Stat Treat 2021;4:187-8
|How to cite this URL:|
Bondili SK, Noronha V, Chougule A, Prabhash K. Authors' reply to Devakumar et al., Katte et al., and Batra et al.. Cancer Res Stat Treat [serial online] 2021 [cited 2021 May 9];4:187-8. Available from: https://www.crstonline.com/text.asp?2021/4/1/187/312116
We thank Devakumar et al., Katte et al., and Batra and Nathany for their interest and valuable suggestions for our manuscript titled, “Resistance mechanisms to epidermal growth factor receptor inhibitors in non-small cell lung cancer.”
Our patient had epidermal growth factor receptor (EGFR)-mutant metastatic adenocarcinoma of the lung and received gefitinib and osimertinib in the first and second lines, respectively. Post disease progression on osimertinib, a next-generation sequencing (NGS)-based analysis of the ascitic fluid cell block revealed a mutation in the CTNNB1 gene along with the EGFR C797S mutation. Devakumar et al. have pointed out that despite the availability of a targetable genomic alteration, we used conventional chemotherapy alone for the treatment. This was because the patient had a considerable disease burden and a borderline performance status of 2, thus necessitating the use of chemotherapy to control the symptom burden. Additionally, information about the type of C797S mutation (cis or trans conformation) was requested from the molecular laboratory, but was not available at the time of treatment initiation. Lastly, since the proposed targeted treatment options did not have sufficient evidence and as the patient had a high disease burden, we preferred the standard treatment option of chemotherapy first and reserved the experimental approaches to a later line after the exhaustion of all the standard treatment options. We agree with Devakumar et al. that EA1045, brigatinib plus cetuximab, and BLU-945 are the treatment options when C797S is in cis with T970M and gefitinib with osimertinib when they are in trans, however, most of these drugs are inaccessible in the Indian setting. Moreover, the combination of gefitinib and osimertinib, albeit tolerable, was not preferred in our patient due to limited evidence of its benefit. In the case reports by Arulananda et al. and Wang et al. on patients treated with the combination of EGFR tyrosine kinase inhibitors (TKIs) and osimertinib, the progression-free survival was modest, at 6 weeks and 3 months, respectively.,
CTNNB1, which is a part of the Wnt/beta-catenin pathway, is frequently mutated in several cancers including colorectal cancer, melanoma, mesothelioma, etc. It is also frequently found to be mutated in adenocarcinoma of the lung and is one of the mechanisms of resistance to EGFR TKIs. We agree with Devakumar et al. that trametinib and bevacizumab can be used to target the CTNNB1 mutations, as shown in a preclinical study and a small phase-I clinical trial, respectively. Therefore, these agents can be considered after exhausting standard therapies., The evidence is more for niclosamide, and it is already being evaluated in a phase-II clinical trial in metastatic colorectal cancer (NCT02519582) and in combination with abiraterone and prednisolone (NCT02807805) in castration-resistant prostate cancer. We concur with Devakumar et al. on their proposed approach [Figure 1], however, more clinical research is required to generate sufficient data for it to be incorporated into routine clinical practice.
We agree with Batra and Nathany, that using techniques with higher sensitivities like digital droplet polymerase chain reaction can identify T790M mutations in the plasma cfDNA much before the actual radiological progression. As the ascitic fluid cell block on progression revealed adenocarcinoma, the possibility of a small cell transformation appeared unlikely. Additionally, we would like to clarify that the NGS panel used included TP53 mutations but not mutations in the RB1 gene. We agree that incorporation of the RB1 gene in the NGS panel could give us a better idea about the possibility of a small cell transformation which might otherwise be missed because of tumor heterogeneity.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Devakumar V, Raut NV, Britto N,. Exploring novel combinations of targeted therapy in the journey of epidermal growth factor receptor-mutant lung cancers. Cancer Res Stat Treat 2021;4:184-5. [Full text]
Katte T, Sirigiri DN, Rasalkar AA. Study of intransigence of the epidermal growth factor receptor in non-small cell lung cancer. Cancer Res Stat Treat 2021;4:185-6. [Full text]
Batra U, Nathany S. Path beyond TKIs- Full of Riddles and Puzzles. Cancer Res Stat Treat 2021;4:182-3. [Full text]
Bondili SK, Nandhana R, Noronha V, Joshi A, Patil V, Menon N, et al
. Resistance mechanisms to epidermal growth factor receptor inhibitors in non-small cell lung cancer. Cancer Res Stat Treat 2020;3:801-7. [Full text]
Arulananda S, Do H, Musafer A, Mitchell P, Dobrovic A, John T. Combination Osimertinib and Gefitinib in C797S and T790M EGFR-Mutated Non-Small Cell Lung Cancer. J Thorac Oncol 2017;12:1728-32.
Wang Z, Yang JJ, Huang J, Ye JY, Zhang XC, Tu HY, et al
. Lung Adenocarcinoma Harboring EGFR T790M and In Trans C797S Responds to Combination Therapy of First- and Third-Generation EGFR TKIs and Shifts Allelic Configuration at Resistance. J Thorac Oncol 2017;12:1723-7.
Montpréville VT, Ayoubi RE, Mamodaly M, Lacroix L, Mercier O, Fadel E, et al
. P1.09-17 CTNNB1 (Beta-Catenin) Mutations in Non-Small Cell Lung Carcinoma: A Clinicopathological Study of 18 Cases. J Thorac Oncol 2018;13:S557.
Uitdehaag JC, Roos JA, Doornmalen AM, Prinsen MB, Spijkers-Hagelstein JA, Vetter JR de, et al
. Selective Targeting of CTNNB1-, KRAS- or MYC-Driven Cell Growth by Combinations of Existing Drugs. PLoS One 2015;10:e0125021.
Aghajanian C, Filiaci V, Dizon DS, Carlson JW, Powell MA, Secord AA, et al
. A phase II study of frontline paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus, or ixabepilone/carboplatin/bevacizumab in advanced/recurrent endometrial cancer. Gynecol Oncol 2018;150:274-81.