ASCO & AACR
The two biggest conferences in the oncology calendar showcased a wealth of data yet again in 2019, the key difference in this year’s ASCO and AACR programs’ was the focus on patient care and learning from every patient; moving away from concentrating predominately on clinical trial data. Tying in with this, health disparities were a major vein of the meetings – sessions explored the socio-economic factors that contribute to survival rates, the impact of the Affordable Care Act and anti-HIV bias in cancer.
In 2019 a pioneering breathalyzer was developed that could revolutionize the way cancer is detected. The breathalyzer works by analyzing exhaled breath samples with potential biomarker volatile organic compounds. This relatively small-in-size breathalyzer is aiming to achieve a monumental mission; saving 100,000 lives and US$1.5 billion in healthcare costs. Find out about the potential financial and health-associated benefits of this technology in this editorial by our columnist Balkees Abderrahman (University of Texas MD Anderson Cancer Center, TX, USA & University of Leeds, UK).
It’s no surprise that CAR-T therapy made the list. In February Kymriah® (tisagenlecleucel) was approved by NICE for diffuse large B-cell lymphoma. Move forward a few months and CAR-T therapy was making waves at the AACR Annual Meeting, with HER2 as well as mesothelin-targeted CAR-T therapy both showing promise. At the ASH Annual Meeting CAR-T therapy also dominated headlines, yielding positive results for lymphoma. We further explored how CAR-T therapy is revolutionizing oncology in Ask the Experts features – focusing on logistics and its potential in solid tumors.
Major news in cancer diagnostics this year centred around blood tests. Early in the year a preliminary study in mice hinted that a blood test could be on the horizon for lung cancer, fast forward and a similar study grabbed the headlines but this time for the detection of glioblastoma. The most read story in this arena came from the 2019 NCRI Cancer Conference, a pilot study reported the development of a blood test that could detect breast cancer up to 5 years before any clinical signs by detecting the presence of tumor-associated antigens, which are indicative of the disease.
Given that EGFR is expressed by many lung cancer tumors, it has become an important therapeutic target. Throughout 2019 the increasing focus on grouping cancers according to their genetic components, rather than their site, fueled the progression of research in this area. One paper we featured on the site delved into tumor clonality and resistance mechanisms to EGFR. Whilst another paper discussed how we can optimize treatment sequencing decisions for patients with EGFR mutation-positive lung cancer.
Once again throughout 2019, our sister journal Future Oncology published key advances in cancer research and highlighted their relevance in the clinical setting. Top-read pieces from the journal included a short communication exploring the GioTag study and a review article discussing optimizing outcomes and treatment sequences in EGFR mutation-positive NSCLC. You can gain access to the most read articles through Rachel Jenkin’s (Editor of Future Oncology and Oncology Central) editorial here.
This year saw a groundbreaking CRISPR study; researchers performed genome-scale CRISPR–Cas9 screens to disrupt every gene in over 300 cancer models from 30 cancer types, revealing thousands of genes essential for cancer growth. This study also unearthed novel gene fusions, presenting new drug targets for tumors such as ovarian and breast cancer. We furthered explored the role of gene fusions in a recent webinar, which you can watch on demand to find out how next-generation sequencing technology can aid fusion detection.
A major clinical trial from 2019 was the ENCORE 601 Phase Ib/II clinical trial, which demonstrated that a combination of the experimental HDAC inhibitor entinostat with the anti-PD-1 therapeutic Keytruda® (pembrolizumab) exhibits clinical responses in melanoma patients who had progressed on prior anti-PD-1 treatment. To find out more about this trial, we spoke with Ryan Sullivan (Massachusetts General Hospital Cancer Center, MA, USA) at the AACR Annual Meeting about his research.
In February, it was announced that isatuximab had met its primary endpoint of prolonging progression-free survival in relapsed/refractory multiple myeloma patients treated with isatuximab in combination with pomalidomide and low-dose dexamethasone vs pomalidomide and low-dose dexamethasone alone (standard of care). Following on from these encouraging results and data presented at the ASCO Annual Meeting, the US FDA is reviewing isatuximab as a treatment option for these multiple myeloma subtypes. We look forward to hearing their decision in April 2020.
JAVELIN Gastric 100
Early in the year, our sister journal Future Oncology published a clinical trial protocol describing the design of the JAVELIN Gastric 100 Phase III trial, which evaluated maintenance avelumab vs continuation of first-line chemotherapy in in gastric cancer patients. The authors hope that the results of this trial will lead to the availability of a new treatment option for these cancers. Later in the year, the trial yielded unfavorable results as avelumab failed to extend overall survival of patients compared to standard care.
Since its arrival Kymriah has caused a stir in oncology; in 2017 the FDA made a historic action by approving it as the first gene therapy in the United States, ushering in a new approach to the treatment of cancer. This approval was then followed by yet more across the pond. In the UK, Kymriah® became the first CAR-T therapy available on the NHS. The commercial deal between NHS England and Novartis was the first in Europe and came less than 10 days after it was granted European marketing authorization; making it one of the fastest funding approvals in the history of the NHS. In early 2019, NICE approved Kymriah for the treatment of diffuse large B-cell lymphoma in adults.
Tying in with the earlier theme of cancer diagnostics, liquid biopsies gained traction this year. At the ASCO Annual Meeting we spoke with Bob Li (Memorial Sloan Kettering Cancer Center, MSKCC NY, USA) about his latest research investigating how ultra-deep next-generation sequencing of plasma circulating cell-free DNA is being used in patients with advanced lung cancers. We also found out outcomes of the basket trial he presented at ASCO that used ado-trastuzumab emtansine to treat salivary gland cancers. To round things off, Li provided insight into the potential of liquid biopsies and their future as a clinical tool, as well as highlighting the important work that still needs to be done to ensure its success.
Over the past few years, the concept of artificial intelligence has gained traction in oncology. This year, interest spiked when a study from the Institute of Cancer Research (ICR, London, UK) utilized artificial intelligence to recognize patterns in breast cancer – and uncovered five new types of the disease, each matched to different personalized treatments. However, alongside the growing interest there has been trepidation about how we can responsibly integrate machine learning into practice and what role big data should play in healthcare – find out more by watching our panel discussion.
The most-read paper of the year from our partnered journals was published in CNS Oncology and reviewed the recommendations of the Response Assessment in Neuro-Oncology (RANO) working groups, investigating how they may be applied in the routine care of patients with different types of brain tumors. For those interested in guidelines for trials or patient care in central nervous system oncology management, this is a key read. This year we also featured a systematic review and meta-analysis that investigated the correlation between serotonin levels and survival in neuroendocrine tumors patients.
Another topic that was highly popular was organoids. In April, researchers from The ICR and The Royal Marsden (London, UK) used organoids to reveal how colorectal cancer cells avoid cibisatamab, a promising immunotherapy. We further explored organoids as a novel and alternative model for cancer research in our Spotlight. One of the most viewed content pieces within this feature was a mini review that questioned the importance of organoids in personalized medicine. To gain further insights into organoids as a model system in oncology, we spoke with Luke Boulter (University of Edinburgh, UK) and David Tuveson (Cold Spring Harbor Laboratory, NY, USA).
In 2019, pembrolizumab’s success saw no signs of slowing down – with positive results being observed in glioblastoma, prostate and small cell lung cancer as well as several more approvals being granted in Europe for its use. Additionally, the drug was approved by the FDA in combination with other therapies for non-small cell lung cancer and renal cell carcinoma. Unfortunately, pembrolizumab also observed unfavorable results from the KEYNOTE-240 trial for advanced hepatocellular carcinoma. The drug did not meet its primary survival endpoints, we await to see how this story develops as other similar trials read out.
Quality of life and outcomes
As more cancer drugs are approved and the disease becomes more treatable, the number of cancer patients who are treatable but not curable is increasing. This patient cohort was highlighted during the NCRI 2019 Cancer Conference in which Paul Cosford (Public Health England, UK) discussed his experience of living with terminal cancer. Tying into this topic, the theme of cancer cost has made the headlines several times; President Trump faced backlash when he announced plans to cut NIH funding and a few months later a huge study investigated whether price growth is being driven by the monopoly pharmaceutical companies have on deciding prices.
Real-world data was previously considered less helpful when the approval of new agents into everyday clinical practice was slow. However, as the approval rate of novel oncology drugs has spiked, modern strategies are now frequently based on real-world evidence. Our most read peek behind the paper feature explored this notion in regards to multiple myeloma. The paper highlighted the importance of incorporating real-world evidence into research as well as top line findings from the INSIGHT MM study and how these findings could affect routine clinical practice. A principal event to bookmark in your calendars next year is Real-World Evidence 2020, organized by our sister-site The Evidence Base, if you would like to find out more.
In 2019, the #MeToo movement brought sexual harassment and assault to the forefront of international media attention. At the Annual ASCO Meeting results from a survey were presented that showed that, of 402 respondents, 64% of members had experienced a form of sexual harassment at some point in their career. “The topic of sexual harassment has been widely discussed in the media… but conversation in the medical community has largely been limited to personal anecdotes discussed behind closed doors,” commented lead study author Marina Stasenko (MSKCC). The authors stated that they hope their findings will raise awareness and lead to future interventions to address gender inequalities.
Tumor mutation burden
Tumor mutation burden (TMB) is a promising predictive biomarker, which could potentially lead the way for immuno-oncology to enter a new era of precision medicine. In the first quarter of the year we shone a light on TMB in our Spotlight. The most popular piece from the feature was by Balkees Abderrahman in which she highlighted the progress that has been made in TMB research across different cancer types – read the full article here. A webinar on a comprehensive genomic tool to evaluate TMB and panel discussion exploring what the future holds for this field wrapped up our Spotlight.
2019 has proved to be yet another busy year for the FDA. In March the first immunotherapy treatment – Tecentriq® (atezolizumab) in combination with Abraxane® – was approved by the FDA for breast cancer. Atezolizumab also gained approval for small-cell lung cancer and as a combination treatment for non-small cell lung cancer. In June, pembrolizumab was granted approval as a first-line treatment for advanced head and neck cancer and the first antibody–drug conjugate was approved to treat diffuse large B-cell lymphoma. A few months later saw rozlytrek (entrectinib) being granted approval to treat tumors with a specific genetic change regardless of cancer type.
Throughout 2019, groundwork was put in place for developing vaccines for various cancer types. First up, researchers analyzed neoantigens on the surface of bowel cancer tumor cells in order to evaluate how well bowel cancer may respond to immunotherapy, the findings are pipped to pave the way for personalized vaccines for this cancer type. Next up, a potential melanoma vaccine was developed as a fast-acting skin patch that efficiently delivers medication to attack melanoma cells and finally the first steps towards creating a pancreatic cancer vaccine were put in place. In 2020 it is hoped that further efforts will see the translation of these lab-based studies into real-world practice.
Women in oncology
Throughout 2019 we have had the honor of working with women at the forefront of advancing cancer research and treatment. At the ASCO Annual Meeting, one of the giants in cancer care Laura Esserman (University of California, San Francisco, CA, USA) partook in our panel discussion along with Carla Balch (Inteliquet, TN, USA), and Edith Mitchell (Sidney Kimmel Cancer Center, PA, USA). Several of our top read articles have been written by Balkees Abderrahman who recently was named as one of The Forbes Under 30 2020 List. We look forward to celebrating the women pushing the field forward in our upcoming International Women’s Day feature!
As hinted at through this A–Z, genomics has progressed oncology significantly over the last year. A key player in this field is next-generation sequencing – during the year we have explored the power of next generation sequencing with respect to identifying predictive biomarkers, fusion detection and the assessment of multiple genomic alterations. Our most recent video explores how comprehensive genomic profiling, enabled by next-generation sequencing, could bring cancer from uncertainty to focus, by allowing all known biomarkers to be evaluated in single test. Watch the video here to find out more from a global team of experts.
The first positive results for Yervoy® (ipilimumab) in 2019 were presented at the AACR Annual Meeting. Results from the DART Phase II clinical trial indicated that a combination of the anti-CTLA-4 immunotherapeutic, Yervoy®, and the anti-PD-1 immunotherapeutic, nivolumab (Opdivo®), may be beneficial to patients with high-grade neuroendocrine carcinoma. Later in the year, yet more promising results were reported at the IASLC World Conference on Lung Cancer but this time for lung cancer patients. The CheckMate 817 trial demonstrated that combining nivolumab with ipilimumab is safe as a first-line therapy for lung cancer patients with other comorbidities such as HIV, brain metastases, kidney and renal disease.
In 2019 Zejula® (niraparib) demonstrated positive results in Phase III PRIMA study for patients with ovarian cancer in the first-line maintenance setting. Around the same time, niraparib was granted Priority Review by the FDA. The competition between AstraZeneca/Merck and GlaxoSmithKline built at the ESMO 2019 Congress, with both sides presenting positive data in this remit. A few months later GlaxoSmithKline experienced a major win when NICE approved the use of niraparib for use via the Cancer Drug Fund for women with relapsed ovarian, fallopian tube or peritoneal cancer, which has responded to platinum-based chemotherapy.
With all the great research and advancements in cancer care in 2019, we’re looking forward to seeing what exciting new discoveries 2020 will hold for oncology!