ALK TKI therapy in patients with ALK-positive non-small cell lung cancer and brain metastases: A review of the literature and local experiences.

This article reviews the role of ALK tyrosine kinase inhibitors (TKIs) in the literature and provides expert commentary on local use in Argentina, Brazil, China, Russia, South Korea, and Turkey. We identified 56 articles involving patients with ALK-positive non-small cell lung cancer (NSCLC) and brain metastases (BM) treated with ALK TKIs published between January 2000 and June 2021. In first-line settings, central nervous system response rates in clinical trials with alectinib (86-94%), brigatinib (67-78%), and lorlatinib (42-82%) were generally higher than those reported with crizotinib (16-71%). Median progression-free survival in patients receiving crizotinib (5.6-7.4 months) was lower than alectinib (not reached), brigatinib (24.0 months), and ceritinib (10.7-25.2 months). Across these counties, next-generation TKIs are preferred for patients with progressing BM lesions. Although next-generation ALK TKIs demonstrate significant activity in these patients and following progression on crizotinib, access remains a challenge for personalized therapy.

Treatment pathways and clinical outcomes in Hodgkin lymphoma outside Europe and North America: results from the international, multicenter, retrospective, B-HOLISTIC study.

Information on Hodgkin lymphoma (HL) is mostly limited to Europe and North America. This real-world, retrospective study assessed treatment pathways and clinical outcomes in adults with stage IIB-IV classical HL receiving frontline treatment (n = 1598) or relapsed/refractory HL (RRHL, n = 426) in regions outside Europe and North America between January 2010 and December 2013. The primary endpoint was progression-free survival (PFS) in the RRHL group. Among patients with RRHL, 89.0% received salvage chemotherapy; most common regimen was etoposide, methylprednisolone, cytarabine, cisplatin (ESHAP; 26.3%). Median PFS in the RRHL group was 13.2 months (95% confidence interval [CI]: 9.9-20.2) and was longer in patients with vs. without stem cell transplantation (SCT; 20.6 vs. 7.5 months; p = 0.0071). This large-scale study identified a lower PFS for RRHL in the rest of the world compared with Europe and North America, highlighting the need for novel targeted therapies and SCT earlier in the treatment continuum.Clinical trial registration: NCT03327571.

Testing for EGFR Mutations and ALK Rearrangements in Advanced Non-Small-Cell Lung Cancer: Considerations for Countries in Emerging Markets.

The treatment of patients with advanced non-small-cell lung cancer (NSCLC) in recent years has been increasingly guided by biomarker testing. Testing has centered on driver genetic alterations involving the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) rearrangements. The presence of these mutations is predictive of response to targeted therapies such as EGFR tyrosine kinase inhibitors (TKIs) and ALK TKIs. However, there are substantial challenges for the implementation of biomarker testing, particularly in emerging countries. Understanding the barriers to testing in NSCLC will be key to improving molecular testing rates worldwide and patient outcomes as a result. In this article, we review EGFR mutations and ALK rearrangements as predictive biomarkers for NSCLC, discuss a selection of appropriate tests and review the literature with respect to the global uptake of EGFR and ALK testing. To help improve testing rates and unify procedures, we review our experiences with biomarker testing in China, South Korea, Russia, Turkey, Brazil, Argentina and Mexico, and propose a set of recommendations that pathologists from emerging countries can apply to assist with the diagnosis of NSCLC.

CD30, CD15, CD50, and PAX5 Expressions as Diagnostic Markers for Hodgkin Lymphoma (HL) and Systemic Anaplastic Large Cell Lymphoma (sALCL).

BACKGROUND: the expression of CD30, CD15, CD50, and PAX5 are used to help in confirming diagnosis of HL and sALCL; however data on the proportion of these markers have not been available. The study was aimed to identify the proportion of CD30, CD15, CD50 and PAX5 expressions and characteristics of patients with HL and sALCL at Dharmais National Cancer Center Hospital between 2005 and 2015. METHODS: a retrospective observational study was conducted using data from medical records and histopathological results of HL and sALCL adult patients who sought treatment at the hospital between 2005 and 2015. Immunohistochemistry (IHC) examinations were performed and data on the proportion of positive CD30, CD15, CD50, and PAX5 expressions were analyzed descriptively. RESULTS: a total of 45 patients were recruited in this study, with the majority (42 patients, 93.3%) were HL patients and only 6.7% were sALCL patients. The median age of HL patients was younger than sALCL patients; 35 (18-72 years old) versus 54 (49-61 years old). Moreover, the immunohistochemistry examination demonstrated that the positive CD15, CD30, CD50, and PAX5 expressions were found respectively in 37.5%, 88.9%, 31.2%, and 31.2% patients with HL; while in patients with sALCL, in spite of their small sample size, positive CD30, CD15, CD50 and PAX5 expressions were found in 100%; 66,7%; 50%; and 50%, respectively. Overall, CD15, CD50, and PAX5 positive expressions were found in 39.5%, 32.4%, and 32.4% patients who had HL and sALCL; while positive expression of CD30 was found in 89.5% of them. CONCLUSION: present study shows that almost 90% patients have positive CD30 expression;  while the positive expressions of CD15, CD50, and PAX5 are found in less than 40% patients. It indicates that CD30 is an important diagnostic marker for HL and sALCL and it may improve treatment strategy.

Clinical Effectiveness, Safety and Tolerability of Amlodipine/Valsartan in Hypertensive Patients: the Indonesian Subset of the EXCITE Study.

AIM: to assess the effectiveness, safety and tolerability of amlodipine/valsartan (Aml/Val) single-pill combination (SPC) in hypertensive patients in a real-world setting. METHODS: the Indonesian subset of the EXCITE (clinical EXperience of amlodIpine and valsarTan in hypErtension) study, which was a multinational, prospective, observational, open study in hypertensive patients treated with Aml/Val SPC for 26 weeks. Aml/Val SPCs (5/80, 5/160, 10/160 mg) were administered as monotherapy or as add-on therapy to other antihypertensive medications in patients not controlled by prior monotherapy. The effectiveness outcomes were (1) mean decrease in sitting systolic blood pressure and diastolic blood pressure (msSBP and msDBP) from baseline to week 26; (2) proportion of patients achieving BP goal (<140/90 mmHg for nondiabetics, or <130/80 mmHg for diabetics); (3) proportion of patients who were responders (achieving BP goal or BP reduction of >20/10 mmHg). The safety variables were the incidence of AEs and SAEs, and the incidence of edema. RESULTS: a total of 500 patients from Indonesia received Aml/Val SPC, 487 patients were analyzed for efficacy (by LOCF), and 464 patients completed the study. At study end (week 26), the overall msSBP and msDBP(95% CI) reductions from baseline were -33.7 (-35.2, -32.1) mmHg and -14.8 (-15.7, -13.8) mmHg, respectively. Among the 487 patients, 52.4% achieved BP goal and 80.5% were responders (LOCF). Among 464 patients who completed the study, 53.7% achieved BP goal and 84.5% were responders. Aml/Val SPC was effective in decreasing BP in Indonesian patients. AEs, including SAEs, were reported in 11.4% patients, with SAEs in 1% of patients, and death in 0.8% of patients. SAEs and deaths were considered unrelated to the study drug. Edema was reported by 9.4% of patients at baseline, and in 3.7% patients at end of study. Effectiveness, tolerability and compliance were rated good and very good in 90.8%, 92.2%, and 89.2% of patients, respectively, according to the investigators. CONCLUSION: Aml/Val SPC was effective for BP reductions and well tolerated in hypertensive patients, not adequately controlled by monotherapy, in a daily clinical setting in Indonesia.