In addition to the two major studies VHIO selected for its media program during last week’s 55th Annual Meeting of the American Society of Clinical Oncology (ASCO), 31 May – 04 June, Chicago – IL, USA, view this previous VHIO news by clicking here, this year’s gathering attracted almost 40, 000 oncologists from across the globe and included more than 2,400 abstracts accepted for presentation, and more than 3,200 additional abstracts accepted for online publication.

Among these, several VHIO-led studies were selected by ASCO to showcase during this momentous, international celebration of clinical and translational cancer science. Furthermore, many VHIO faculty were also picked to feature on the program as invited speakers and/or session (co) Chairs.

For a consecutive year, VHIO’s Director and President of the European Society of Medical Oncology (ESMO), Josep Tabernero, co-chaired a Special Session on Global Health entitled: ASCO/ESMO Joint Session – Global Access to Essential Medicines, alongside ASCO’s President, Monica M. Bertagnolli, Dana-Farber/Brigham and Women’s Cancer Center (DF/BWCC), Boston – MA, USA.

Commencing with Nicola Magrini, Invited Speaker from the World Health Organization, the stage was superbly set by her presentation on Global Access to Essential Medicines. A panel of internationally renowned experts then discussed and debated varying perspectives and challenges from the US and European points of view, as well as the hotly debated topic surrounding the pricing and performance of anti-cancer therapies. This was followed by a special Q&A round with the panel.

 

A hand-pick of just some of the many VHIO studies that showcased during ASCO 2019:

Novel NALA III

Selected for an Oral Abstract Session of the Metastatic Breast Cancer Track, the multi-center phase III NALA trial, directed by first author VHIO’s Cristina Saura, Principal Investigator of our Breast Cancer Group, was designed to assess a novel treatment strategy for patients with HER2+ metastatic breast cancer who had previously received two or more prior HER2 targeted regimens.

The study compared neratinib with lapatinib, both tyrosine kinase inhibitors that interrupt the HER2 pathway, in combination with capecitabine. A total of 621 patients participated in this trial and results showed that combined treatment with neratinib and capecitabine significantly improved progression-free disease compared to the combination with lapatinib.

Commenting on the findings Cristina said, “We observed a reduction in both the risk of disease progression by 24%, and even mortality in the first group of patients treated with neratinib in combination.” The trial also showed promise in delaying the onset of neurological symptoms resulting from metastases.

 

Immune-based strategies against lung cancer 

Novel immune-based therapies, including immune checkpoint inhibitors, and increasingly in combination, continue to significantly improve patient outcomes across many cancers – most notably to-date in treating melanoma and non-small cell lung cancer (NSCLC).

Regarding the latter, Enriqueta Felip, Principal investigator of our VHIO Thoracic Tumors & Head and Neck Cancer Group, first authored two studies that were selected to first outing as posters, on immunotherapeutic-based strategies aimed at more effectively combating lung cancer. Also selected for coverage on the ground by oncology channel, ecancer, she presented preliminary results from a phase II study of bemcentinib, a first-in-class highly selective AXL inhibitor, in combination with pembrolizumab, a monoclonal antibody directed against PD-1, in patients with advanced NSCLC.

AXL is a tyrosine kinase receptor implicated in epithelial-mesenchymal transition, which is reactivated during tumor progression and a mechanism of resistance to multiple treatments, including anti-PD1 therapy. Overall, the researchers observed that the combination of both was well tolerated and showed promising clinical activity. Specifically, in patients with AXL-positive tumors a 35 percent response rate was achieved, with a 20 percent rate observed for patients with PD-L1 negative tumors.

Discussing these results, Enriqueta said, “These preliminary findings are encouraging and merit further studies. This combination could be particularly relevant for patients who have been selected by AXL.”

Enriqueta also presented results from a study on whole exome sequencing of NSCLC to assess tumor mutational burden (TMB) and identify the long-term benefit of treatment with immune checkpoint inhibitors.

This research, driven purely by VHIO researchers and clinical investigators, showed that that TMB correlates with the long-term benefit of these immune-based therapy in patients with NSCLC. Importantly in the quest to more accurately matching individual patients to tailored treatment strategies, mutations in individual genes were shown to be likely linked long-term benefit or resistance to these inhibitors.

Speaking more broadly about the promise versus performance of immune-based anti-cancer medicines she observed, “These novel agents are certainly here to stay as we investigate further how to potentiate and personally tailor this anti-cancer armory to unleash the power of and individual’s immune system to mount an attack on cancer.”  She concluded, “We must also collectively establish why some cancers do not respond or eventually become resistant to treatments, and, in parallel, identify more faithful predictors of response.”

 

Practice changing in ‘the pipeline’

As first author, VHIO’s Ana Oaknin, Principal Investigator of our Gynecological Malignancies Group, presented a poster on a phase III academic, multicenter trial — results of which could ultimately prove practice changing.

This study, promoted by the Spanish Ovarian Cancer Research Group (GEICO) – for which Ana also serves as Vice-President – is running under the umbrella of the European Network for Gynaecological Oncology Trial Groups (ENGOT), and spans sites across Europe, Japan and the US. Designed to assess a novel combinatorial therapeutic strategy aimed at improving outcomes for patients with advanced cervical cancer: A randomized, open label, phase III study of cisplatin and paclitaxel chemotherapy with bevacizumab with or without atezolizumab as first-line treatment for metastatic, persistent, or recurrent carcinoma of the cervix, this clinical research seeks to improve outcomes for these patients, for whom there are currently very few effective therapeutic options available.

Commenting for VHIO Communications Ana, who is also global lead of the study, said, “We hope to provide new hope for our patients with recurring advanced cervical cancer by combining immune-checkpoint inhibitor atezolizumab with first-line choice of treatment that pairs chemotherapy with targeted therapy bevacizumab.  

She continued, “With patient enrolment scheduled to complete next year, we are hoping to rapidly establish thereafter whether this immunotherapy, that has already proven promising for the more effective treatment of other tumor types, also benefits our particular patient population when administered with this combination.”

 

Gender and cancer treatment decisions

Over recent years, multiple initiatives sought to more firmly integrate gender into oncology to analyze the biological differences between sexes and more precisely tailor treatments accordingly. A frequent clinical observation is that toxicity differs between men and women, but there is scarce evidence of this reported in the scientific literature.

Jorge Hernando, Clinical Investigator and Medical Oncologist of VHIO’s Gastrointestinal and Endocrine Tumours Group headed by Teresa Macarulla and directed by Josep Tabernero, presented as study, led by Jaume Capdevilla, also a Clinical Researcher of the same group, to better explore this rapidly emerging area.

This work assessed the differential toxicity between men and women with pancreatic and gastrointestinal neuroendocrine tumors treated with multikinase inhibitors, with data from two phase II trials conducted by the Spanish Group of Neuroendocrine and Endocrine Tumors (GETNE), with pazopanib and lenvatinib. Importantly, this is first international study of its kind in patients with neuroendocrine tumors.

The team found that there are 8 differential toxicities between men and women: 7 more common in women (liver toxicity, headache, dizziness, heartburn, nausea, skin and hair disorders), and 1 more commonly observed in men (dysphonia).

“These data will enable us to more precisely prevent as well as treat toxicities by gender. Our plan is to extend our approach to new clinical trials, and invite other investigators to prospectively do the same,” said Jorge Hernando.

To access our other recent news, Headlining at ASCO’s 2019 Annual Meeting: VHIO driving advances against gastrointestinal tumors, highlighting two other studies that were selected for VHIO’s media program please click here.

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