|LETTER TO EDITOR
|Year : 2021 | Volume
| Issue : 2 | Page : 401-402
Second-line nivolumab for patients with metastatic renal cell carcinoma in India: A call for expanding global access to clinical trials
Nicholas J Salgia1, Ameish Govindarajan2, Sumanta Kumar Pal2
1 Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA; Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA
2 Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA
|Date of Submission||14-Apr-2021|
|Date of Decision||16-Apr-2021|
|Date of Acceptance||14-May-2021|
|Date of Web Publication||30-Jun-2021|
Sumanta Kumar Pal
Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA 91010
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Salgia NJ, Govindarajan A, Pal SK. Second-line nivolumab for patients with metastatic renal cell carcinoma in India: A call for expanding global access to clinical trials. Cancer Res Stat Treat 2021;4:401-2
|How to cite this URL:|
Salgia NJ, Govindarajan A, Pal SK. Second-line nivolumab for patients with metastatic renal cell carcinoma in India: A call for expanding global access to clinical trials. Cancer Res Stat Treat [serial online] 2021 [cited 2021 Jul 24];4:401-2. Available from: https://www.crstonline.com/text.asp?2021/4/2/401/320230
For years, the treatment algorithm for metastatic renal cell carcinoma (mRCC) was based on the use of targeted therapies, particularly vascular endothelial growth factor receptor tyrosine kinase inhibitors (TKIs) in the first-line setting and beyond. Despite their impressive survival data compared to the previous regimens, these agents offered little to no opportunity for cure. This paradigm was disrupted with the advent of immune checkpoint inhibitors (ICIs). The CheckMate-025 trial was the first phase-III study on the use of ICIs in mRCC, that showed improved progression-free survival (PFS) and overall survival (OS) with nivolumab, which targets the programmed death receptor-1, compared to everolimus in the refractory disease setting. This trial provides the framework for the study published by Abbas et al. in Cancer Research, Statistics, and Treatment.
Abbas et al. utilized a real-world dataset of patients with mRCC who received second-line nivolumab after progression on a TKI at a tertiary cancer center in India. A total of 19 patients who fulfilled these criteria were retrospectively identified. The median PFS was 8 months (95% confidence interval [CI], not evaluable) and OS was 13 months (95% CI, 10.4–15.5), with a objective response rate (ORR) of 26.3%. Adverse events were reported in 69% of the patients, with grade 3/4 events occurring in 11% of the cohort. The response rate data from Abbas et al.'s study are comparable to those reported in the CheckMate-025 trial (ORR of 25%). However, it is also important to note the differences in the results of these two studies. The PFS in Abbas et al.'s study far exceeds that in the CheckMate-025 (8 months vs. 4.6 months) trial, whereas the OS was remarkably lower (13 months vs. 25.0 months).
These efforts from Abbas et al. offer a practical perspective on the utility of ICIs in the treatment-refractory setting for patients with mRCC in India. The authors observed that nivolumab was both safe and efficacious in this population. This and similarly guided works are important in part due to the lack of representation of these populations in the pivotal trials. For example, in the CheckMate-025 trial, of the total 821 participants, none were Indian. Thus, the data form Abbas et al.'s study provide key insights into the utility of ICIs in this demographically distinct population.
The approach to treatment of mRCC has dramatically changed over the past 5 years and is now anchored by ICI use in the front-line with regimens such as nivolumab/ipilimumab, pembrolizumab/axitinib, and nivolumab/cabozantinib, among others. None of the six key trials for the front-line use of ICIs in mRCC enrolled participants from investigatory sites in India. Based on this shift in the disease management and lack of demographic representation in trials, it is imperative that similar studies be undertaken to analyze the utility of front-line ICIs in these populations.
Although limited in scope, this study provides important context and support for the use of ICIs following disease progression on a first-line TKI for patients with mRCC in India. Further prospective work is warranted as is additional real-world investigation into the activity of front-line ICIs in mRCC in similar populations. India once was a hub of clinical trial enrollment, however, recent regulations and patient skepticism have limited the investment in clinical trial infrastructure in the country. This study may provide a framework and justification for restoring this infrastructure and including historically underrepresented demographic groups in future clinical research endeavors.
Financial support and sponsorship
Conflicts of interest
Nicholas Salgia and Ameish Govindarajan declare that they have no conflicts of interest that might be relevant to the contents of this manuscript. Sumanta K. Pal, MD: Honoraria-Novartis, Medivation, Astellas Pharma; Consulting or Advisory Role-Pfizer, Novartis, Aveo, Myriad, Pharmaceuticals, Genentech, Exelixis, Bristol-Myers Squibb, Astellas Pharma; Research Funding-Medivation.
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