|LETTER TO THE EDITOR
|Year : 2021 | Volume
| Issue : 4 | Page : 788-789
Old targets, new bullets, nursing fresh hope
Homi Bhabha Cancer Hospital and Research Centre, Visakhapatnam, Andhra Pradesh, India
|Date of Submission||31-Oct-2021|
|Date of Decision||06-Nov-2021|
|Date of Acceptance||08-Nov-2021|
|Date of Web Publication||29-Dec-2021|
Door No. 9-6-39/1, High School Road, New Gajuwaka, Visakhapatnam - 530 026, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Ventrapati P. Old targets, new bullets, nursing fresh hope. Cancer Res Stat Treat 2021;4:788-9
Batra and Nathany have elaborately reviewed the role of KRAS in human carcinogenesis in their article titled, “Biomarker series: KRAS-A narrative review,” and Agrawal et al. have comprehensively reviewed the new drug, sotorasib, in their article titled, “Sotorasib– an inhibitor of KRAS p. G12c mutation in advanced non-small cell carcinoma: A narrative drug review.” I congratulate the authors for their extensive reviews and would like to share my opinion about the same.
It is no secret that the advent of targeted agents, especially against epidermal growth factor receptor, anaplastic lymphoma kinase, ROS, and Mesenchymal Epithelial Transition (MET) genes in lung cancer over the past two decades has revolutionized the treatment protocols, and drastically improved outcomes. KRAS was one of the earliest proto-oncogenes to be detected and is one of the most common genes to be mutated in colorectal, pancreatic, and lung cancers. Yet, it took almost 40 years for mankind to make the “undruggable” KRAS finally druggable. The response rates and disease control rates of sotorasib against the G12C mutant cancers in heavily pretreated patients are remarkable and offer a new glimmer of hope in this setting.
Although this breakthrough has been encouraging, there are certain aspects which should not be forgotten. First, the issue of the hurried Food and Drug Administration approval with the scanty available data reminds us of how nascent we still are in the war against cancer and of the long road ahead to victory, especially because of the unavailability of any other promising therapy in this setting and the need for more concrete evidence required to firmly establish its role.
Second, although colorectal, and pancreatic cancers have a higher proportion of RAS mutations, even after years of research, it is still disappointing to see the meager response rates in these cancers. Now that we have a targeted drug, more focused research is required to study the factors implicating outcomes in these patients, and it will be wonderful if we are able to control the disease with targeted therapies similar to lung cancers.
Third, in the Indian context, we should think how relevant this breakthrough is for us. The pertinent question is how many eligible patients will be able to procure the drug? For example, promising drugs such as osimertinib and immunotherapy in lung cancer are probably utilized by <10% of the eligible patients in our country. Right now, sotorasib costs more than $15,000 a month. How long will it be before it becomes affordable for Indian patients with cancer and will we actually be able to reap the benefits?, The average per capita national income in our country is around ₹12,000/month and most of the health expenditure is out-of-pocket, creating an enormous gap in the adoption of these new treatment regimens., A monumental policy decision by the government will probably be required for the Indian patients to benefit from these drugs, but that is easier said than done. Still, it would be wonderful to see these effective treatments within our reach.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Batra U, Nathany S. Biomarker series: KRAS – A narrative review. Cancer Res Stat Treat 2021;4:516-23. [Full text]
Agrawal AK, Pragya R, Choudhary A, Gupta A, Sambasivaiah K, Mishra BK, et al
. Sotorasib – An inhibitor of KRAS p.G12c mutation in advanced non-small cell carcinoma: A narrative drug review. Cancer Res Stat Treat 2021;4:524-8. [Full text]
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. [Full text]
Kapoor A, Noronha V, Shetty O, Chougule A, Chandrani P, Patil VM, et al.
Molecular tumor board: Case 2 – Evolution of resistance in anaplastic lymphoma kinase driven non-small-cell lung carcinoma. Cancer Res Stat Treat 2020;3:89-92. [Full text]
Kapoor A, Noronha V, Chougule A, Patil VM, Menon N, Joshi A, et al.
Molecular tumor board: Case 1-Interplay of EGFR, MET and PD-L1 in non-small cell lung carcinoma. Cancer Res Stat Treat 2019;2:228-31. [Full text]
Prabhash K, Vora A, Limaye S, Sahoo TP, Batra U, Patil S, et al.
Treatment of advanced non-small-cell lung cancer: First line, maintenance, and second line – Indian consensus statement update (Under the aegis of Lung Cancer Consortium Asia, Indian Cooperative Oncology Network, Indian Society of Medical and Pediatric Oncology, Molecular Oncology Society, and Association of Physicians of India). Cancer Res Stat Treat 2021;4:279-314. [Full text]
Beganovic S. Clinical significance of the KRAS mutation. Bosn J Basic Med Sci 2009;9 Suppl 1:17-20.
Aga SS, Nissar S. RAS mutations and colorectal cancer: Testing and precision medicine. Cancer Res Stat Treat 2021;4:580-1. [Full text]
Shetty O. Exploring RAS mutations in Indian patients with colorectal cancer: Have we seen it all? Cancer Res Stat Treat 2021;4:365-7. [Full text]
Hong DS, Kuo J, Sacher AG, Barlesi F, Besse B, Kuboki Y, et al.
CodeBreak 100: Phase I study of AMG 510, a novel KRASG12C inhibitor, in patients (pts) with advanced solid tumors other than non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). J Clin Oncol 2020;38 Suppl 15:3511.
Radhakrishnan V. Drug pricing: A major barrier to access to cancer care in India. Cancer Res Stat Treat 2021;4:195-7. [Full text]
Philip CC, Mathew A, John MJ. Cancer care: Challenges in the developing world. Cancer Res Stat Treat 2018;1:58-62. [Full text]
Ahlin T, Nichter M, Pillai G. Health insurance in India: What do we know and why is ethnographic research needed. Anthropol Med 2016;23:102-24.
Goyanka R. Economic and non-economic burden of cancer: A propensity score matched analysis using household health survey data of India. Cancer Res Stat Treat 2021;4:29-36. [Full text]