Most Read Articles
14 Feb 2020
The phase III CASTOR and POLLUX studies previously demonstrated benefit of daratumumab plus bortezomib and dexamethasone (DVd) or lenalidomide and dexamethasone (DRd) vs standard-of-care (SoC) Vd or Rd regimen in relapsed or refractory multiple myeloma (R/R MM). The latest efficacy and safety results after 4 years of follow-up from CASTOR and POLLUX were presented at the American Society of Hematology (ASH) 61st Meeting & Exposition 2019 held in Orlando, Florida, US.  
Prof Winnie Yeo, 03 Aug 2020
Despite the availability of antiemetics, a substantial proportion of patients receiving chemotherapy experience chemotherapy-induced nausea and vomiting (CINV), significantly impacting treatment compliance and quality of life (QoL). At the 24th Annual Scientific Symposium of the Hong Kong Cancer Institute, Professor Winnie Yeo of the Department of Clinical Oncology, Chinese University of Hong Kong, presented results of a local study showing superior efficacy of the fixed-dose netupitant/palonosetron (NEPA) combination regimen vs aprepitant-based regimen in controlling CINV in breast cancer patients receiving highly emetogenic anthracycline-cyclophosphamide (AC) chemotherapy.
Dr. Michael Tsz-Yeung Kam, 04 Jun 2020

Third-generation EGFR tyrosine kinase inhibitors (TKIs) targeting the EGFRT790M mutation, such as osimertinib, have brought significant improvements to the management of EGFR-positive non-small-cell lung cancer (NSCLC). However, optimization of EGFRT790M mutation testing remains challenging in clinics. At a symposium organized by the Hong Kong Cancer Therapy Society, Dr Michael Tsz-Yeung Kam, Specialist in Clinical Oncology in Hong Kong, discussed real-world challenges in EGFRT790M testing and the current workflow at his centre.

Dr. Herman Sung-Yu Liu, 03 Aug 2020
Although first- and second-generation tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukaemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL), resistance or intolerance to these agents has limited their effectiveness, particularly in patients who harbour the BCR-ABLT315I mutation. In an interview with MIMS Oncology, Dr Herman Sung-Yu Liu, Specialist in Haematology & Haematological Oncology in private practice in Hong Kong, discussed the management of CML and Ph+ ALL using the third-generation TKI, ponatinib, the only agent in its class with activity against the T315I mutation. 

RT plus immunotherapy holds potential for sarcoma treatment

Natalia Reoutova
19 Nov 2019
Prof Angela Hong

Advances in radiotherapy (RT) and immuno-oncology are poised to benefit sarcoma patients, many of whom do not respond to chemotherapy.

“While neoadjuvant and adjuvant RT is used for local control of soft tissue sarcoma [STS], it does not improve overall survival due to its inability to reach micrometastases,” said Professor Angela Hong of the University of Sydney in Sydney, Australia.

The immune system is found to play a role in RT response. In a study using a B16-SIY melanoma mouse model, nude mice’s tumours did not respond to RT, while wild-type mice with depleted CD8+ T lymphocyte levels showed some tumour response, but not of the same extent as wild-type controls. [Blood 2009;16:589-595].

“RT achieves an in situ vaccination effect by releasing tumour antigens, danger-associated molecular proteins, proinflammatory cytokines [IL-1β, TGF, FGF, TNF] and chemokines,” explained Hong. In addition, changes in endothelium enhance immune cell extravasation, causing local infiltration of dendritic cells, macrophages, antigen-specific T cells, as well as myeloid derived suppressor cells. Phenotypic analyses of antigen-specific CD8+ T cells reveal that RT increases the percentage of antigen-experienced effector memory T cells. [Lancet Oncol 2015;16:498-509; Cancer Immunol Res 2015;3:345-355]

Preclinical studies combining RT and immunotherapy have shown intriguing results, including effects outside of the radiation field – a phenomenon termed abscopal effect. Originally, immune-mediated abscopal effects were documented in contralateral shielded tumours after administering RT with Flt3-L. [Cancer Res 1999;59:6028-6032; Int J Radiat Oncol Biol Phys 2004;58:862-870] Subsequently, combining RT with anti–CTLA-4 antibody in breast and colorectal carcinoma mouse models produced abscopal effects that correlated with the frequency of interferon (IFN)γ+ CD8 T cells. [Clin Cancer Res 2009;15:5379-5388]

Moreover, melanoma and non-small-cell lung cancer (NSCLC) case reports provided evidence of synergy between RT and immune checkpoint blockade. [N Engl J Med 2012;366:925-931; Cancer Immunol Res 2013;1:365-372]

“Clinical data on the use of immunotherapy in STS, especially when combined with RT, is lagging behind melanoma and lung cancer, as it is a much rarer cancer. Therefore, international collaboration is necessary to recruit a sufficient number of patient to translate into an impactful clinical trial,” remarked Hong.

To date, two phase II trials have shown promising results of immunotherapy in STS. Nivolumab plus ipilimumab attained a 16 percent objective response rate (ORR) with a manageable safety profile, comparable to currently available treatment options, in the Alliance A097401 study, while pembrolizumab achieved an ORR of 18 percent and a 12-week progression-free survival rate of 55 percent in the SARC028 trial. [Lancet Oncol 2018;19:416-426; Burgess MA, et al, ASCO 2017, abstract 11008] SARC032 is an ongoing phase II trial of neoadjuvant pembrolizumab with RT and adjuvant pembrolizumab for high-risk STS. [Mowery YM, et al, ASCO 2018, abstract TPS11588]

Recent genomic studies have established different mutational burdens across sarcoma histologies. Genetically complex STS subtypes, such as undifferentiated pleomorphic sarcoma (UPS) and leiomyosarcoma (LMS), have high expression levels of genes related to antigen presentation and T‐cell infiltration, and may therefore be more likely to respond to immunotherapies. [Cancer 2017;123:3291-3304] Interestingly, the highest ORR (40 percent) attained in the SARC028 trial was within the UPS cohort treated with pembrolizumab, but no responses were observed among LMS patients. [Burgess MA, et al, ASCO 2017, abstract 11008]

“For most high-grade STS cases, traditional chemotherapy is of limited benefit, especially in the metastatic setting. The combination of immunotherapy with RT, which synergistically stimulate a systemic antitumour immune response, has the potential to improve survival through eliminating micrometastases,” concluded Hong.

Digital Edition
Asia's trusted medical magazine for healthcare professionals. Get your MIMS Oncology - Hong Kong digital copy today!
Sign In To Download
Editor's Recommendations
Most Read Articles
14 Feb 2020
The phase III CASTOR and POLLUX studies previously demonstrated benefit of daratumumab plus bortezomib and dexamethasone (DVd) or lenalidomide and dexamethasone (DRd) vs standard-of-care (SoC) Vd or Rd regimen in relapsed or refractory multiple myeloma (R/R MM). The latest efficacy and safety results after 4 years of follow-up from CASTOR and POLLUX were presented at the American Society of Hematology (ASH) 61st Meeting & Exposition 2019 held in Orlando, Florida, US.  
Prof Winnie Yeo, 03 Aug 2020
Despite the availability of antiemetics, a substantial proportion of patients receiving chemotherapy experience chemotherapy-induced nausea and vomiting (CINV), significantly impacting treatment compliance and quality of life (QoL). At the 24th Annual Scientific Symposium of the Hong Kong Cancer Institute, Professor Winnie Yeo of the Department of Clinical Oncology, Chinese University of Hong Kong, presented results of a local study showing superior efficacy of the fixed-dose netupitant/palonosetron (NEPA) combination regimen vs aprepitant-based regimen in controlling CINV in breast cancer patients receiving highly emetogenic anthracycline-cyclophosphamide (AC) chemotherapy.
Dr. Michael Tsz-Yeung Kam, 04 Jun 2020

Third-generation EGFR tyrosine kinase inhibitors (TKIs) targeting the EGFRT790M mutation, such as osimertinib, have brought significant improvements to the management of EGFR-positive non-small-cell lung cancer (NSCLC). However, optimization of EGFRT790M mutation testing remains challenging in clinics. At a symposium organized by the Hong Kong Cancer Therapy Society, Dr Michael Tsz-Yeung Kam, Specialist in Clinical Oncology in Hong Kong, discussed real-world challenges in EGFRT790M testing and the current workflow at his centre.

Dr. Herman Sung-Yu Liu, 03 Aug 2020
Although first- and second-generation tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukaemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL), resistance or intolerance to these agents has limited their effectiveness, particularly in patients who harbour the BCR-ABLT315I mutation. In an interview with MIMS Oncology, Dr Herman Sung-Yu Liu, Specialist in Haematology & Haematological Oncology in private practice in Hong Kong, discussed the management of CML and Ph+ ALL using the third-generation TKI, ponatinib, the only agent in its class with activity against the T315I mutation.