Most Read Articles
Natalia Reoutova, 20 May 2020

Cancer patients infected with coronavirus disease 2019 (COVID-19) appear to be at higher risk of severe outcomes, including death, but cancer type and treatment serve as better predictors, according to recent research presented at the American Association for Cancer Research (AACR) 2020 Virtual Annual Meeting I.

At the time of writing, COVID-19 has spread to more than 200 countries and territories, affecting an estimated 4.5 million people and killing over 300,000. Cancer, on the other hand, is newly diagnosed in 18 million people and takes the lives of 10 million every year.

“We have invited physician scientists who are at the epicentre of the COVID-19 pandemic, taking care of patients with cancer. They gathered prospective information to understand the effects of COVID-19 on patients with cancer, are testing new treatments, and are making this knowledge available to the global research community, so we can all benefit from their experience,” said Professor Antoni Ribas from UCLA Medical Center, Los Angeles, California, US, chairperson of the COVID-19 and cancer plenary session of the meeting.

Natalia Reoutova, 4 days ago

Fasting-mimicking diet (FMD) cycles in combination with endocrine therapy (ET) cause metabolic changes in hormone receptor (HR)-positive breast cancer patients analogous to those observed in animal models, where they are associated with anticancer activity.

Dr. Jason Butler, 01 Apr 2020
Proteasome inhibitors have become a cornerstone of therapy for multiple myeloma (MM). At the Hong Kong Society of Myeloma Annual Scientific Meeting 2019, Dr Jason Butler of the Icon Cancer Care & Royal Brisbane and Women’s Hospital, Brisbane, Australia, reviewed current evidence for the use of proteasome inhibitors in the management of relapsed/refractory MM (R/R MM), with a focus on the efficacy and safety profile of carfilzomib.
Natalia Reoutova, 3 days ago

Results of the world’s first-in-human phase I clinical trial of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 PD-1–edited T cells, recently published in Nature Medicine, suggest therapy’s feasibility in refractory non-small-cell lung cancer (NSCLC), with no severe treatment-related adverse events (TRAEs).

PD-L1 inhibitors and the future of metastatic Merkel cell carcinoma management

Prof. Mark Shackleton
Monash University, Australia
01 Apr 2020
In recent years, the focus on immuno-oncology has generated a wealth of compelling evidence supporting the use of immune checkpoint inhibitors – in particular those targeting the programmed death-ligand 1 (PD-L1) or PD-1 pathway. At the 8th Oncology Summit organized by the Hong Kong Society of Clinical Oncology, Professor Mark Shackleton of Alfred Health and Monash University, Australia, discussed recent advances in immunotherapy for the management of metastatic Merkel cell carcinoma (MCC) with a focus on the role of the PD-L1 inhibitor avelumab.  
“Metastatic MCC is often an aggressive and fatal disease as it typically presents in elderly patients, the majority of them with comorbidities and other age-related issues,” said Shackleton.

While MCC is a relatively rare cancer, its global incidence has increased over the past few decades. “It remains unclear if this trend is due to the ageing global population, or if it is simply due to increased awareness and diagnoses,” he noted. [Onco Targets Ther 2015;8:2157-2167; J Am Acad Dermatol 2018;78:457-463] 

“An accurate diagnosis of MCC is important not just to rule out other possibilities such as small-cell cancer or metastases from other sites, but also to determine cancer stage as this can open treatment and clinical trial options for patients,” Shackleton noted. [J Natl Compr Canc Netw 2018;16:742-774]

“With MCC, the key to diagnosis lies in the immunohistochemistry panel,” stressed Shackleton, noting that classic markers for MCC include CD20 and AE1/AE3 positivity, and TTF1 and CK7 negativity. [Surg Cosmet Dermatol 2016;8:266-270] “However, about 5 percent of MCC cases are negative for cytokeratin 20 (CK20). Of these CK20-negative MCC cases, 77 percent are Merkel cell polyomavirus [MCPyV]-negative [and thus typically associated with ultraviolet (UV) light exposure]. In regions with high UV exposure such as Australia, only about 24 percent of MCC cases are MCPyV-positive.” [Br J Dermatol 2011;165:1051-1057; Mod Pathol 2015;28:498-504]

Current treatment landscape

According to the 2018 US National Comprehensive Cancer Network (NCCN) guidelines, complete surgical excision is the recommended primary treatment for localized MCC, typically followed by radiation. [J Natl Compr Canc Netw 2018;16:742-774] “Sentinel lymph node biopsy is generally indicated for these patients as the information obtained can inform the extent of post-excision radiation,” said Shackleton. [J Natl Compr Canc Netw 2018;16:742-774] “While not indicated by the NCCN guidelines, we would suggest considering adjuvant radiation to the involved nodal bed for patients who are sentinel lymph node–positive.” [J Natl Compr Canc Netw 2018;16:742-774]

“At present, there is no standard recommendation for adjuvant systemic chemotherapy for the treatment of stage 1–3 [locoregional] MCC. While the NCCN notes that platinum-containing regimens may be used on a case-by-case basis, this has yet to be validated in randomized controlled trials,” he continued. “Additionally, use of adjuvant chemotherapy in the absence of a proven survival benefit is questionable for elderly patients with comorbidities.” [J Natl Compr Canc Netw 2018;16:742-774; Cancers (Basel) 2014;6:1180-1194]

Immunotherapy the “game-changer” in metastatic MCC

There is evidence that immunosuppressed individuals are at higher risk of MCC compared to the general population. [Cancers 2013;5:234-254; Br J Cancer 2009;101:1444-1447] “Additionally, MCPyV oncoproteins are a major contributor to MCC pathogenesis and the immune response to these oncoproteins appears to include elevated expression of PD-L1 proteins in MCC,” said Shackleton. [Cancers 2014;6:1180-1194] “Interestingly, high PD-L1 expression in MCC might be associated with improved prognosis.” [Cancer Immunol Res 2013;1:54-63]

“These observations have led to a number of promising clinical studies of PD-1 inhibitors in MCC,” noted Shackleton. “For instance, a phase II study demonstrated a rapid and high rate of response to pembrolizumab in previously untreated patients, while another demonstrated good pathologic response rates and long-term survival with neoadjuvant nivolumab in patients with resectable disease.” [J Clin Oncol 2019;37:693-702; J Clin Oncol 2018;36(15 suppl):9505]

Avelumab: An excellent first-line option for metastatic MCC

“Avelumab is a human anti–PD-L1 monoclonal antibody, with antibody-dependent cellular cytotoxicity [ADCC], that has been approved for the treatment of metastatic MCC since 2017. It was the first treatment approved by the US FDA for patients with metastatic MCC,” noted Shackleton. [Bavencio (avelumab) injection [package insert], Merck KGaA, 2017] “Avelumab has since been approved in multiple countries, including Japan, Australia and Canada, for first- or second-line treatment of metastatic MCC, largely due to compelling data from the JAVELIN Merkel 200 study.” [Australian Public Assessment Report for Avelumab. Therapeutic Goods Administration (TGA): Australia, 2019; https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/notice-compliance/conditions/qualifying-notice-bavencio-204052.html]

In the phase II JAVELIN Merkel 200 study, patients with metastatic MCC whose disease had progressed on or after chemotherapy received avelumab (10 mg/kg intravenously, every 2 weeks) and were followed up for a median of 29.2 months. “The results were impressive, with an overall response rate [ORR] of 33 percent and durable responses in 19 of 29 patients, including 12 whose duration of response exceeded 2 years,” noted Shackleton. [Nghiem P, et al, ASCO 2018, abstract 9507]“The median overall survival [OS] was 12.9 months, and the 2-year OS rate was 36 percent.” [Nghiem P, et al, ASCO 2018, abstract 9507; J Immunother Cancer 2018;6:7]

“While subgroup analyses suggested a higher probability of response in patients who had received fewer prior lines of systemic therapy and were PD-L1–positive, durable responses occurred irrespective of baseline factors, including MCPyV status,” he noted. [J Immunother Cancer 2018;6:7]

The companion study – JAVELIN Merkel 200 Part B – which is ongoing, evaluates the use of avelumab in the first-line setting. A preplanned interim analysis of the trial reported an objective response rate of 62.1 percent. In patients who responded, 93 percent had a maintained response at 3 months, and 83 percent responded for at least 6 months. (Table) [JAMA Oncol 2018;4:e180077]

“In JAVELIN Merkel 200 Part B, 21 of 30 patients [70 percent] had at least 30 percent reduction in target lesions from baseline,” noted Shackleton. “To date, no grade 4 treatment-related adverse events or deaths have been reported, and adverse events were either grade 1 or 2, infusion-related and manageable.” [JAMA Oncol 2018;4:e180077]

“In addition to being approved for first-line treatment of metastatic MCC in multiple countries worldwide, the strength of this data led to avelumab’s approval for public funding in the Pharmaceutical Benefits Scheme [PBS] in Australia in January 2019,” said Shackleton. [http://www.pbs.gov.au/industry/listing/elements/pbac-meetings/psd/2018-07/files/avelumab-psd-july-2018.pdf] "This was a significant milestone for avelumab and highlights how impressive the JAVELIN data are, as the PBS rarely approves treatments whose benefits have not been demonstrated in a phase III trial against standard therapy.”

 HK-MER-218mo  

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Most Read Articles
Natalia Reoutova, 20 May 2020

Cancer patients infected with coronavirus disease 2019 (COVID-19) appear to be at higher risk of severe outcomes, including death, but cancer type and treatment serve as better predictors, according to recent research presented at the American Association for Cancer Research (AACR) 2020 Virtual Annual Meeting I.

At the time of writing, COVID-19 has spread to more than 200 countries and territories, affecting an estimated 4.5 million people and killing over 300,000. Cancer, on the other hand, is newly diagnosed in 18 million people and takes the lives of 10 million every year.

“We have invited physician scientists who are at the epicentre of the COVID-19 pandemic, taking care of patients with cancer. They gathered prospective information to understand the effects of COVID-19 on patients with cancer, are testing new treatments, and are making this knowledge available to the global research community, so we can all benefit from their experience,” said Professor Antoni Ribas from UCLA Medical Center, Los Angeles, California, US, chairperson of the COVID-19 and cancer plenary session of the meeting.

Natalia Reoutova, 4 days ago

Fasting-mimicking diet (FMD) cycles in combination with endocrine therapy (ET) cause metabolic changes in hormone receptor (HR)-positive breast cancer patients analogous to those observed in animal models, where they are associated with anticancer activity.

Dr. Jason Butler, 01 Apr 2020
Proteasome inhibitors have become a cornerstone of therapy for multiple myeloma (MM). At the Hong Kong Society of Myeloma Annual Scientific Meeting 2019, Dr Jason Butler of the Icon Cancer Care & Royal Brisbane and Women’s Hospital, Brisbane, Australia, reviewed current evidence for the use of proteasome inhibitors in the management of relapsed/refractory MM (R/R MM), with a focus on the efficacy and safety profile of carfilzomib.
Natalia Reoutova, 3 days ago

Results of the world’s first-in-human phase I clinical trial of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 PD-1–edited T cells, recently published in Nature Medicine, suggest therapy’s feasibility in refractory non-small-cell lung cancer (NSCLC), with no severe treatment-related adverse events (TRAEs).