Immune checkpoint inhibitors: Real-world experience from India in advanced solid cancers that have progressed on chemotherapy

Abstract

Context: The immune checkpoint inhibitors (ICIs) nivolumab and pembrolizumab have shown dramatic efficacy with low toxicity in international studies of advanced solid cancers. No published Indian experience with ICIs exist other than isolated case reports. Aims: The aim of this study is to evaluate real-world data about the efficacy and toxicity of ICIs in advanced solid cancers among Indian patients who have progressed on one or more prior lines of chemotherapy. Materials and Methods: All patients with advanced solid cancers who received ICIs after the failure of chemotherapy at our center were retrospectively assessed. Information about efficacy and toxicity was collected and analyzed. Results: The present study included 24 patients who had received ICIs for indications including non-small cell lung, bladder, head and neck, gastrointestinal, and unknown primary cancer. Patients had received a median of two prior lines of chemotherapy (range 1–5). Grade III or higher toxicity was seen in 8% of patients. Clinical benefit at 3 months was realized in 33% of evaluable patients. Twenty-six percentages of evaluable patients achieved a response, including one patient who achieved a complete response that is ongoing at 18 months. Median progression-free survival was 3 months, and median overall survival was 8 months at a median follow-up of 10 months. Among patients who achieved clinical benefit, the majority (84%) have an ongoing response at the time of data cutoff. Conclusions: Efficacy and toxicity of ICIs in the Indian population are similar to the experience seen in large international cohorts, and Indian oncologists may feel reassured using these agents in similar settings.

Key words

Bladder cancer - head-and-neck cancer - immunotherapy - lung cancer - metastatic cancer - nivolumab - oral cancer - pembrolizumab

Publication History

Article published online:
31 December 2020

• References

• 1 Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin Oncol 2015;33:1974-82.
• 2 Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 2015;372:2018-28.
• 3 Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 2016;375:1823-33.
• 4 Horn L, Spigel DR, Vokes EE, Holgado E, Ready N, Steins M, et al. Nivolumab versus docetaxel in previously treated patients with advanced non-small-cell lung cancer: Two-year outcomes from two randomized, open-label, phase III trials (CheckMate 017 and checkMate 057). J Clin Oncol 2017;35:3924-33.
• 5 Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cezll lung cancer. N Engl J Med 2015;373:123-35.
• 6 Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee JL, Fong L, et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med 2017;376:1015-26.
• 7 Sharma P, Retz M, Siefker-Radtke A, Baron A, Necchi A, Bedke J, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): A multicentre, single-arm, phase 2 trial. Lancet Oncol 2017;18:312-22.
• 8 Ferris RL, Blumenschein G, Fayette J, Guigay J, Colevas AD, Licitra L, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 2016;375:1856-67.
• 9 Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017;390:2461-71.
• 10 Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015;372:2509-20.
• 11 For Indian Cancer Patients, Immunotherapy is Way Pricey; 2017. Available from: https://www.deccanchronicle.com/; https://www.deccanchronicle.com/lifestyle/health-and-wellbeing/280717/for-indian-cancer-patients-immunotherapy-is-way-pricey.html. [Last accessed on 2018 Apr 27].
• 12 Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med 2018;378:158-68.
• 13 Aggarwal S, Minhas S, Shinde S, Ganvir M. Complete remission in an elderly patient of advanced-stage squamous cell carcinoma lung with nivolumab: An exceptional case study from India. Int J Case Rep Images 2017;9:51-5.
• 14 Chandrakanth MV, Noronha V, Joshi A, Patil V, Mahajan A, Prabhash K, et al. Nivolumab instills hope in a hopeless situation in advanced nonsmall cell lung cancer with poor performance status. Indian J Cancer 2017;54:55-6.
• 15 Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med 2018; 378:2078-92.
• 16 Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med 2017;377:1919-29.
• 17 Gupta VG, Bakhshi S. Pediatric hematopoietic stem cell transplantation in India: Status, challenges and the way forward: Based on dr. K. C. Chaudhuri oration 2016. Indian J Pediatr 2017;84:36-41.
• 18 Haanen JB, Carbonnel F, Robert C, Kerr KM, Peters S, Larkin J, et al. Management of toxicities from immunotherapy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017;28:iv119-42.
• 19 Moslehi JJ, Salem JE, Sosman JA, Lebrun-Vignes B, Johnson DB. Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet 2018;391:933.
• 20 Braschi-Amirfarzan M, Tirumani SH, Hodi FS Jr., Nishino M. Immune-checkpoint inhibitors in the era of precision medicine: What radiologists should know. Korean J Radiol 2017;18:42-53.