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Osimertinib in Indian Patients with T790M‑Positive Advanced Nonsmall Worsening 17%

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Osimertinib in Indian Patients with T790M‑Positive Advanced Nonsmall Worsening 17% Published online: 2020-12-22 Ram, et al.: Male breast cancer Conclusion 4. Shukla NK, Seenu V, Goel AK, Raina V, Rath GK, Singh R, et al. Male breast cancer: A retrospective study from a regional cancer center in Carcinoma breast in male management principles are translated Northern India. J Surg Oncol 1996;61:143-8. from our understanding of breast cancer in women. The prognosis 5. Mitra D, Manna A, Sikdar SK, Sur PK. Clinicopathological study and its is dependent on stage of the disease and HR status. Most of the prognostic implication in male breast carcinoma. J Indian Med Assoc 2007;105:681-3, 686. analysis in our study was in concordance with the available data 6. Chikaraddi SB, Krishnappa R, Deshmane V. Male breast cancer in Indian except the stage at presentation. In our study, the predominant stage patients: Is it the same? Indian J Cancer 2012;49:272-6. at presentation was Stage II. This may be due to raising awareness 7. Shah P, Robbani I, Shah O. Clinicopathological study of male breast among the population in the metro cities, which is a welcome trend. carcinoma: 24 years of experience. Ann Saudi Med 2009;29:288-93. 8. Rai B, Ghoshal S, Sharma SC. Breast cancer in males: A PGIMER Financial support and sponsorship experience. J Cancer Res Ther 2005;1:31-3. Nil. 9. Mukherjee A, Saha A, Chattopadhyay S, Sur P. Clinical trends and outcomes of male breast cancer: Experience of a tertiary oncology centre Conflicts of interest in India. Int J Cancer Ther Oncol 2014;2:20-35. There are no conflicts of interest. 10. Sundriyal D, Kotwal S, Dawar R, Parthasarathy KM. Male breast cancer in India: Series from a cancer research centre. Indian J Surg Oncol References 2015;6:384-6. 1. Anon. Available at: Fact Sheets by Cancer; 2017. Available from: http:// 11. Gogia A, Raina V, Deo SV, Shukla NK, Mohanti BK. Male breast cancer: www.globocan.iarc. fr/Pages/fact_sheets_cancer.aspx. [Last accessed A single institute experience. Indian J Cancer 2015;52:526-9. on 2017 Apr 20]. 12. de Perrot M, Deléaval J, Robert J, Spiliopoulos A. Thirty-year 2. Anon. Available at: What are the Key Statistics about Breast Cancer experience of surgery for breast carcinoma in men. Eur J Surg in Men? 2017. Available from: http://www.cancer.org/cancer/ 2000;166:929-31. breastcancerinmen/ detailedguide/breast-cancer-in-men-key-statistics. 13. Tawil AN, Boulos FI, Chakhachiro ZI, Otrock ZK, Kandaharian L, [Last accessed on 2017 Apr 20]. El Saghir NS, et al. Clinicopathologic and immunohistochemical 3. Fentiman IS, Fourquet A, Hortobagyi GN. Male breast cancer. Lancet characteristics of male breast cancer: A single center experience. Breast 2006;367:595-604. J 2012;18:65-8. Letter to the Editor No Change 8% Osimertinib in Indian patients with T790M‑positive advanced nonsmall Worsening 17% cell lung cancer Better DOI: 10.4103/sajc.sajc_202_17 75% Dear Editor, The recent AURA3 trial[1] has renewed hopes in the management of T790M mutation‑positive advanced lung cancer. Osimertinib, an irreversible, oral tyrosine kinase Figure 1: Clinical response (n=12) inhibitor (TKI) directed at both epidermal growth factor receptor (EGFR) and T790M mutation, used in advanced Progressive T790M mutation‑positive nonsmall cell lung cancer (NSCLC) disease showed median progression‑free survival of 10.1 months 9% compared with 4.4 months in patients treated with platinum‑pemetrexed. Given this background, we report our first experience of osimertinib in 13 patients of T790M Stable disease Partial Response mutation‑positive advanced NSCLC. 36% 55% We administered Osimertinib 80 mg once daily in 13 T790M‑positive patients in the relapsed setting. Complete hemogram, liver and renal function tests, urine routine, and ECG for QTc prolongation were monitored. Majority of the Figure 2: Radiological response (n=11) patients were women (8) and nonsmokers (11). The types of EGFR mutation at the time of diagnosis included in‑ [Figure 1]. Eleven out of 13 patients had radiological frame deletion in exon 19 (6, 46%), L858R point mutation response evaluation. By revised RECIST 1.1 criteria, in exon 21 (6, 46%) and 1 (8%) upfront T790M mutation. 6/11 (55%) had partial response, 4/11 (37%) had stable 12 patients had received oral TKI (gefitinib/erlotinib) for a disease, and 1 had progressive disease as the best response median duration of 11.2 months (range: 4.6–20.8 months) [Figure 2]. Reason for treatment discontinuation in two before osimertinib. Ten out of 13 patients had received ≥2 patients was clinical progression in one and the Grade 3 lines of therapy. toxicity in the other. Nine of the 13 (70%) reported no Median duration of follow‑up was 2.5 months treatment‑related toxicity. Grade I/II rash was seen in three (range 1.4–5.7 months). 9 of 12 patients experienced a patients. Two patients had Grade I/II thrombocytopenia. One reduction in symptoms after starting therapy with osimertinib patient after 2.2 months of therapy developed Grade 3 (Continue on page 146...) South Asian Journal of Cancer ♦ Volume 6 ♦ Issue 4 ♦ October-December 2017 143 Ostwal, et al.: Tolerance with sorafenib in Indian patients with HCC our patients (43.6%). More importantly, 38.5% of our patients countries. A significant proportion of patients required cessation required interruption or cessation of sorafenib in the initial of sorafenib due to adverse events in our series. Despite the 4 months of treatment, and further, 41% required permanent adverse event profile, EFS remains on par with that seen in cessation due to intolerable side effects. This percentage larger studies with sorafenib in advanced HCC. constitutes a significant proportion of patients who are unable to Financial support and sponsorship tolerate the initial standard recommended dose of 800 mg/day. Nil. While evidence for starting treatment at a lower dose in a Conflicts of interest select group of patients does not exist, there is some evidence There are no conflicts of interest. that patients who are exposed to sorafenib for longer periods, although at lower doses, do better than patients who are unable References 1. Wilhelm S, Carter C, Lynch M, Lowinger T, Dumas J, Smith RA, et al. to receive the drug for longer durations. This is based on post hoc Discovery and development of sorafenib: A multikinase inhibitor for analysis of the SOFIA study, where an increase in survival was treating cancer. Nat Rev Drug Discov 2006;5:835-44. seen in patients who received a half‑dose of sorafenib for more 2. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, et al. Efficacy and than 70% of the treatment period compared with patients who safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: A phase III randomised, double-blind, received either full‑dose or half‑dose of sorafenib for <70% of the placebo-controlled trial. Lancet Oncol 2009;10:25-34. treatment period (21.6 vs. 9.6 months).[4] This also makes the case 3. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. for ensuring compliance and continuing sorafenib even at lower Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378-90. doses, if tolerance is an issue. 4. Iavarone M, Cabibbo G, Piscaglia F, Zavaglia C, Grieco A, Villa E, et al. The assessment of survival outcomes was not one of the Field-practice study of sorafenib therapy for hepatocellular carcinoma: A prospective multicenter study in Italy. Hepatology 2011;54:2055-63. primary end‑points of this study, due to the short planned 5. Gupta S, Gudapati R, Gaurav K, Bhise M. Emerging risk factors for follow‑up. However, the median event free survival of cardiovascular diseases: Indian context. Indian J Endocrinol Metab 4.2 months is on par with published data and is a reinforcement 2013;17:806-14. of sorafenib being the current standard of treatment in 6. Qin C, Cao Q, Li P, Wang S, Wang J, Wang M, et al. The influence of genetic variants of sorafenib on clinical outcomes and toxic effects in patients unresectable HCC not feasible for LDTs. with advanced renal cell carcinoma. Sci Rep 2016;6:20089. 7. Ren Z, Zhu K, Kang H, Lu M, Qu Z, Lu L, et al. Randomized controlled trial Conclusion of the prophylactic effect of urea-based cream on sorafenib-associated Monitoring of Indian patients while on sorafenib for HCC is hand-foot skin reactions in patients with advanced hepatocellular important due to the higher incidence of adverse events seen. carcinoma. J Clin Oncol 2015;33:894-900. 8. Van Hootegem A, Verslype C, Van Steenbergen W. Sorafenib-induced liver There is a higher incidence of liver dysfunction and HFSR failure: A case report and review of the literature. Case Reports Hepatol in Indian patients than seen with published data from other 2011;2011:941395. (Letter to the editor continue from page 143...) esophagitis and hyponatremia requiring discontinuation Vanita Noronha, Swaratika Majumdar, Amit Joshi, of osimertinib. He was again started on osimertinib after Vijay Patil, Vaishakhi Trivedi, Anuradha Chougule, interruption but did not tolerate osimertinib even as an Kumar Prabhash Department of Medical Oncology, Tata Memorial Hospital, Mumbai, alternate day dosing. Maharashtra, India In the AURA3 study[1] in which osimertinib was compared Correspondence to: Dr. Kumar Prabash, to pemetrexed‑platinum therapy in patients with T790M E‑mail: [email protected] positive advanced NSCLC after first‑line oral TKI therapy, the Reference 1. Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, et al. objective response rate to osimertinib was 71% (95%CI, 65 to Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer.
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