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Angioimmunoblastic T-cell lymphoma (AITL) is a histological subtype of peripheral T-cell lymphoma associated with a poor prognosis. This post-hoc pooled analysis aims to provide insight about the efficacy of pralatrexate monotherapy in a subset of twenty-nine patients with relapsed or refractory (r/r) AITL drawn from two prospective registration trials completed in China and Japan. After a median of two prior lines of therapy, an overall response rate of 52% (15/29 patients; 95% CI 0.34, 0.70) was demonstrated. The estimated median duration of response, progression free survival (PFS) and overall survival (OS) were 6.4 months (196 days), 5.0 months (151 days), and 18.0 months (548 days), respectively. Grades 1-3 mucositis was observed in twenty-three patients (79.3%); and hemato-toxicity in twenty-six (89.7%) patients. Results of this analysis corroborate with data from two previously reported US retrospective cohorts, supporting the potential benefits of pralatrexate monotherapy in patients with r/r AITL.

Introduction While patients with r/r TCL have a poor prognosis, significant progress has been made over the past decade in developing new drugs and regimens for the disease. All of the approved agents have their own distinct advantages and issues, making it essential to critically assess the merits and limitations of each. It is well accepted that the development of acquired drug resistance to conventional chemotherapy reduces efficacy with each subsequent line of therapy. However in the era of novel single agents, less is known about the role of these new drugs in patients with chemo-sensitive and chemo-refractory disease. Based on results of the PROPEL trial in 111 treated patients, pralatrexate was the first drug approved as a novel single agent in the US for r/r TCL (O'Connor et al. J Clin Oncol. 2011). Drug registration and approval of pralatrexate was subsequently attained in many healthcare ministries around the world, including Japan, China and Taiwan based on the results of PROPEL and/or locally conducted studies (Maruyama et al. Cancer Sci 2017; Hong et al. Target Oncol 2019; Wang et al. EHA 2019). A meta-analysis of these four trials was undertaken to better understand those factors influencing efficacy and safety of pralatrexate in this patient population. Methods Patient- or summary-level data presented in the individual clinical study reports from the four regulatory-mandated prospective clinical trials of pralatrexate monotherapy in patients with r/r TCL were included in this meta-analysis. Pooled studies (phase 2 PDX-008 [PROPEL], phase 3 FOT12-CN-301, phase 4 FOT14-TW-401, phase 2 part of PDX-JP1) collected data on the primary efficacy endpoint of objective response rate (ORR) as assessed by central review. Secondary efficacy endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Data were collected in accordance with the original protocol and updated with longer survival follow-up where available. Relapse was defined as achieving a complete response (CR) or partial response (PR) on prior therapy lasting for > 3 months, and refractory was defined as stable disease or progressive disease on prior therapy or relapsed disease Results A total of 221 patients were included in the efficacy analysis set for this meta-analysis. The median age was 59 years (range 21-89) and 67% were male. Histological subtypes as assessed by the central review included PTCL-not otherwise specified (108 pts, 49%), angioimmunoblastic T-cell lymphoma (47 pts, 21%), anaplastic large cell lymphoma (ALK-negative; 26 pts, 12%), transformed mycosis fungoides (12 pts, 5%), extranodal NK/T cell lymphoma, nasal type (7 pts, 3%), and other/missing (10/11 pts, 5% each). Patients had a median of 2 prior lines of systemic therapies (range 1-14). At the most recent line of therapy prior to pralatrexate, 68 (31%) and 103 (47%) patients were classified as relapsed and refractory respectively, with the remaining 50 (23%) unable to be determined due to response to the prior therapy being unavailable or not evaluable. Ten percent (n=24) of patients had stem cell transplant prior to receiving pralatrexate. Pooled ORR of the entire cohort was 40.7% (95% CI, 34.2, 47.5), including 30 in CR (13.6%) and 60 in PR (27.2%). The median DOR was 9.1 months (95% CI, 7.4-10.8). Median PFS was 4.6 months (95% CI, 4.0-5.2) while median OS was 16.3 months (95% CI, 13.1-22.6). Conclusions This meta-analysis confirms significant clinical activity of pralatrexate in heavily treated patients with r/r TCL, with an ORR of 40.7% at a median of two lines of prior therapy. These findings meaningfully bolster the original observations from PROPEL with 3 additional regulatory mandated clinical studies and suggest that earlier use may be associated with improved outcome. Further details on the efficacy by prior lines of systemic therapy as well as safety data will be presented. Disclosures O'Connor: TG Therapeutics: Current Employment, Current equity holder in publicly-traded company; Merck: Research Funding; BMS: Research Funding; Astex: Research Funding; Kymera: Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Research Funding; Mundipharma: Honoraria; Myeloid Therapeutics: Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees. Maruyama: Novartis: Research Funding; Chugai: Honoraria, Research Funding; Amgen: Research Funding; BMS: Honoraria, Research Funding; Astellas Pharma,: Research Funding; Otsuka: Research Funding; MSD: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Ono: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Mundipharma: Honoraria; Kyowa Kirin: Honoraria; Zenyaku: Honoraria; AstraZeneca: Honoraria; Nippon: Honoraria; SymBio: Honoraria. Yeoh: Mundipharma: Current Employment. Tobinai: Celgene: Consultancy, Honoraria; Chugai Pharmaceutical: Honoraria; Eisai: Honoraria; Daiichi Sankyo: Consultancy, Honoraria; HUYA Bioscience International: Consultancy, Honoraria; Kyowa Kirin: Honoraria; Mundipharma: Consultancy, Honoraria; Ono Pharmaceutical: Consultancy, Honoraria; Solasia Pharma: Honoraria; Takeda Pharmaceutical: Consultancy, Honoraria; Yakult: Honoraria; Zenyaku Kogyo: Consultancy, Honoraria.

Background: AITL, a histological nodal subtype of peripheral T-cell lymphoma (PTCL), is associated with a poor prognosis, particularly in the r/r setting, underscoring the need for effective salvage therapy. Small patient numbers coupled with a paucity of prospective studies evaluating treatment for r/r AITL provides little information for treatment decision-making. Pralatrexate is the first single agent approved globally in the United States for r/r PTCL based on the pivotal PROPEL trial, which was associated with an 8% (95% CI, 0 to 36%) objective response rate (ORR) in the thirteen r/r AITL patients (O'Connor et al, J Clin Oncol. 2011). Since then, two similar regulatory-mandated prospective trials in North Asian patients have been completed in China (Phase III, single-arm) and Japan (Phase I/II, single-arm). While the final follow-up for each of this study is still ongoing, the primary results were recently published, of which interestingly the former and latter AITL subgroups demonstrated an ORR of 55% (Hong et al, Target Oncol 2019) and 44% (Maruyama et al, Cancer Sci 2017) respectively. Method: A post-hoc meta-analysis of patient level data pooled from these two trials conducted in China and Japan comprising of only r/r AITL patients was undertaken to provide insights about its efficacy and safety in this sub-population. r/r AITL was defined as having failed at least one prior line of therapy, with no upper limit on the number of prior therapies. Treatment-related adverse events of interest included in our analysis were oral mucositis/stomatitis and hematological toxicities (defined as any one of the following: anemia, decreased hemoglobin, granulocytopenia, leukopenia, lymphopenia, neutropenia/febrile neutropenia, pancytopenia, and thrombocytopenia). Cochran's Q-test and I2 were performed to investigate the existence of study heterogeneity. Results: From the total of 96 PTCL patients in the pivotal China (n=71) and Japan (n=25) studies, 29 patients were identified with AITL histology of which twenty were Chinese and nine Japanese. Median age at diagnosis was 62 years (range: 42-83 years). 48% (14 out of 29) of the study population were male. With a median of 2 prior lines of therapy, the ORR was 52% (15/29 patients; 95% CI, 34 to 70%). The median duration of response and overall survival were 4.5 months (136 days) and 9.7 months (295 days), respectively. Twenty-three patients (79.3%) experienced Grades 1-3 oral mucositis / mucositis / stomatitis and twenty-six (89.7%) experienced a hematological toxicity. Conclusion: Though still of limited sample size, our results demonstrated antitumor activity with pralatrexate in r/r AITL patients, of which its safety and tolerability profile in this histological subtype corroborated with the general PTCL population as reported across the studies. Figure Disclosures Zhu: Mundipharma: Research Funding. Yeoh:Mundipharma: Employment. Maeda:Astellas Pharma Inc.: Research Funding; Mundipharma Co Ltd.: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; Kyowa Kirin Co. Ltd.: Honoraria.

Overexpression of the epidermal growth factor receptor-related gene ErbB2 occurs in 18% to 25% of patients with breast cancer in Western countries and is associated with a poor prognosis. The prevalence of ErbB2-positive tumors in Asia is unclear, partly because data are limited. The objective of this review was to summarize the reported prevalence of ErbB2-positive tumors from a large sample of Asian patients and to examine ErbB2 assessment methods in Asia. From searches of MEDLINE, local language journals, and local and international conference proceedings as well as locoregional breast cancer experts' recommendations, the authors selected up to 5 studies each from India, Korea, Malaysia, the Philippines, Singapore, Taiwan, and Thailand that reported ErbB2 results based on assessment with immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH). The reported prevalence of ErbB2-positive tumors in 22 studies on 24,671 patients, of whom 14,398 patients were assessed for ErbB2 status, varied widely (range, 6%-65%) as did the assessment methods used. Most studies (n = 21) used IHC to assess ErbB2 status, but definitions for positivity varied. When robust assessment methods were used, the median prevalence was 19% based on strong IHC staining (IHC3+; n = 9812 patients) and 25% based on FISH (n = 681 patients). Data on the prevalence of ErbB2-positive breast cancer in Asia are limited. The current survey indicated that the prevalence in Asia may be similar to that in Western countries; thus, up to 1 in 4 Asian patients with breast cancer potentially could benefit from ErbB2-targeted treatment. A standard, reliable ErbB2 assessment method available to patients across Asia is urgently required. Cancer 2010;116:5348–57. © 2010 American Cancer Society.

Asia has a disproportionate share of the world's burden of hepatocellular carcinoma (HCC). However, the highly regarded clinical practice guidelines and recommendations for the design and conduct of clinical trials for HCC largely reflect Western practice. In order to design mutually beneficial international clinical trials of promising targeted therapies, it is imperative to understand how the aetiology, staging and treatment of HCC differ between Asian and Western countries. Our group, comprising experts in oncology and hepatology from countries that constitute the Eastern Asian region, convened to compare and contrast our current practices, evaluate potential compliance with the clinical trial recommendations, and offer suggestions for modifications that would enhance international collaboration. Here, we describe the results of our discussions, including recommendations for appropriate patient stratification based on potentially important differences in HCC aetiology, identification of practices that may confound interpretation of clinical trial outcomes (traditional Chinese medicine; antivirals that target hepatitis B virus; heterogeneous embolization procedures), suggestions for utilizing a common staging system in study protocols, recognition that sorafenib usage is limited by financial constraints and potentially increased toxicity in Asian patients, and expansion of patient populations that should be eligible for initial clinical trials with new agents.

The largest burden of hepatocellular carcinoma (HCC) lies in Asia, secondary to hepatitis B virus (HBV) infection. Improved survival with sorafenib has fostered new research but many challenges remain in designing clinical trials. The disease, its management, and populations affected by it are heterogeneous worldwide and within Asia. An expert conference of Eastern Asian oncologists and hepatologists was convened to foster consensus in clinical trial design. The panel identified key areas that need to be addressed to facilitate clinical trials in Asia. Stratification by viral etiology is desirable within Asia and by region in global trials. Antiviral therapy should also be considered as a stratification factor and incorporated into HCC management in trials. The panel agreed that histological diagnosis is not required for trial entry and that Barcelona-Clinic Liver Cancer (BCLC) staging is acceptable for trials as long as portal hypertension can be better defined with standardized methodology. Consensus in treatment must be sought to allow multi-national trials and it must be recognized that first-line sorafenib is not largely feasible in Asia. Finally, Asian nations must be urged to participate in clinical trials, many of which are ongoing, to advance new treatment options in this challenging disease.

Asia has a disproportionate share of the world's burden of hepatocellular carcinoma (HCC). However, the highly regarded clinical practice guidelines and recommendations for the design and conduct of clinical trials for HCC largely reflect Western practice. In order to design mutually beneficial international clinical trials of promising targeted therapies, it is imperative to understand how the aetiology, staging and treatment of HCC differ between Asian and Western countries. Our group, comprising experts in oncology and hepatology from countries that constitute the Eastern Asian region, convened to compare and contrast our current practices, evaluate potential compliance with the clinical trial recommendations, and offer suggestions for modifications that would enhance international collaboration. Here, we describe the results of our discussions, including recommendations for appropriate patient stratification based on potentially important differences in HCC aetiology, identification of practices that may confound interpretation of clinical trial outcomes (traditional Chinese medicine; antivirals that target hepatitis B virus; heterogeneous embolization procedures), suggestions for utilizing a common staging system in study protocols, recognition that sorafenib usage is limited by financial constraints and potentially increased toxicity in Asian patients, and expansion of patient populations that should be eligible for initial clinical trials with new agents.