Ramucirumab in Stage IV non-small-cell lung cancer: Indian data : Cancer Research, Statistics, and Treatment

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Letter to the Editor

Ramucirumab in Stage IV non-small-cell lung cancer

Indian data

Kothari, Rushabh K.

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Cancer Research, Statistics, and Treatment 5(2):p 346-347, Apr–Jun 2022. | DOI: 10.4103/crst.crst_41_22
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Non-small-cell lung cancer (NSCLC) is one of the leading causes of death from malignancy.[12] Unfortunately, it is detected at an advanced stage in the majority of patients and systemic therapy is the backbone of treatment. Chemotherapy, immunotherapy, tyrosine kinase inhibitors, and vascular endothelial growth factor (VEGF) inhibitors are among the established medications in the armamentarium for lung cancer.[3]

Angiogenesis is an important pathway in lung cancer, and anti-VEGF drugs, including bevacizumab and ramucirumab, are approved for usage in the first and second lines, respectively. REVEL was a phase 3 study in the second-line setting in advanced NSCLC that compared ramucirumab + docetaxel versus placebo + docetaxel and showed a statistically significant progression-free survival (PFS) advantage from the addition of ramucirumab. In the Mar 2022 issue of the journal, Prabhash et al. have analyzed the Indian patient subgroup for baseline characteristics, safety, and efficacy.[4]

The authors should be congratulated for providing these important data on Indian patients, as we know that Western data cannot be directly extrapolated to our patients. We noted the promising efficacy of the combination therapy manifested by the longer median PFS (5.6 vs. 1.5 months) and median overall survival (13.5 vs. 5.3 months). Due to the small number of patients, a formal comparison was not performed; however, these values did give us an idea regarding efficacy.[3]

It is important to note that there were significant dose delays (63.6% vs. 21.9%) and dose reductions (22.7% vs. 6.3%) in the study arm.[3] In addition, the financial toxicity of ramucirumab cannot be ignored in a country like ours.[5] We should note that though ramucirumab may be used in squamous cell carcinoma, the efficacy is lower. Bevacizumab, another VEGF inhibitor, leads to an increased risk of pulmonary hemorrhage in squamous cell carcinoma. I request the authors to comment on whether there was an increased bleeding risk in patients with squamous cell carcinoma who received ramucirumab.

Now that immunotherapy is approved in the first- and second-line settings, it is unclear where ramucirumab should be positioned in the therapeutic landscape of advanced NSCLC. Although the response rate of the docetaxel and ramucirumab combination is higher than that of single-agent checkpoint inhibitors (CPI),[6] the chance of long-term survival, equivalent cost, and lower toxicity of CPI is something which will continue to attract patients/physicians.

There are some questions that come up persistently, and we would appreciate the authors' comments on these: What is the role of ramucirumab post-bevacizumab progression? Is ramucirumab worthwhile in squamous cell carcinoma? Can it be combined with drugs other than docetaxel, especially if the patient has received prior taxane therapy? and finally: Where should ramucirumab be placed in the CPI era?

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Conflicts of interest

There are no conflicts of interest.


1. Globocan. India Cancer 2020. 2020 Available from: https://gco.iarc.fr/today/data/factsheets/populations/356-india-fact-sheets.pdf. [Last accessed on 2021 Jan 22]
2. Shetty R, Mathew RT, Vijayakumar M. Incidence and pattern of distribution of cancer in India: A secondary data analysis from six population-based cancer registries Cancer Res Stat Treat. 2020;3:678–82
3. 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
4. Prabhash K, Doval DC, Rangarajan B, Somani N, Pruthi A, Dyachkova Y, et al A multicenter, double-blind, randomized phase III trial of ramucirumab plus docetaxel versus placebo plus docetaxel for treatment of stage IV non-small cell lung cancer after disease progression on or after platinum-based therapy (REVEL): An Indian patient subgroup analysis Cancer Res Stat Treat. 2021;4:634–41
5. Gupta A, Gyawali B. Digging deeper into cancer-associated financial toxicity in low-and middle-income countries Cancer Res Stat Treat. 2021;4:172–3
6. Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, et al Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer N Engl J Med. 2015;373:123–35
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