The remarkable success of first line combined immunochemotherapy in patients with mesothelioma was far from guaranteed until research in Australia managed to demonstrate its potential to improve survival outcomes beyond standard care.
The anticipated findings from the single arm phase 2 DREAM trial were widely reported in September last year. It showed the combination of durvalumab, cisplatin, and pemetrexed had the promising activity and safety signals required to warrant the conduct of a randomised phase 3 trial.
The finding was the culmination of decades-long work from Medical Oncologist Professor Anna Nowak, which has gone on to inform the international phase 3 DREAM3R trial.
Last week during the MOGA scientific meeting the medical oncologist, researcher, advocate and mentor received the inaugural Professor M. Tattersall Heroes Award recognising courage, spirit and commitment to the profession.
“It’s so rewarding to be recognised for some of the things that many people do but that aren’t measured – they’re quite invisible yet they feel very important and meaningful when we do them -particularly when it’s around mentoring young oncologists, and service to the discipline. So, to be recognised for things that are so personally rewarding, it’s just fabulous,” she told the limbic following the announcement.
Professor Nowak has led transformative research in mesothelioma with profound and far-reaching impacts on people with the fatal condition.
Experimental work from her PhD showed that chemotherapy and immunotherapy were synergistic, which has ultimately led to the development of three clinical trials of chemo-immunotherapy in mesothelioma, including the positive DREAM clinical trial and the international DREAM3R trial. She also championed the practice changing CheckMate- 743 trial.
‘I started on this journey in my PhD in 1999 and at that time the combination of chemo-immunotherapy was considered quite fringe. So from having results out of my PhD that were really counterintuitive to working over a number of years in an area that actually took a lot of fighting to get to the point of doing clinical trials and to see those results come through is incredibly fulfilling.”
DREAM was carried out in 10 hospitals around Australia involving 54 patients with advanced mesothelioma who were considered unsuitable for cancer surgery.
Professor Nowak and her team aimed to evaluate the activity of the (PD-L1) checkpoint inhibitor, durvalumab, combined with standard first-line chemotherapy used in MPM.
“We must have attempted to get between five and 10 different drugs for use as a chemo-immunotherapy combination. We really wanted to use checkpoint blockade so durvalumab, which we’re also using in DREAM3R and which we used in DREAM, and is what we hypothesised would combine well with chemotherapy. But of course mesothelioma is quite a rare cancer.
“From a patient’s perspective this is a uniformly fatal cancer but from a pharmaceutical industry perspective it’s a rare disease so that was our biggest challenge – persuading people that this research, in a relatively rare disease, was worthwhile.”
The team’s unwavering persistence paid off. Eventually securing support for supply of the drug therapy for the trial, she began recruiting patients in December 2016.
Early results presented at the American Society for Clinical Oncology (ASCO) Congress in Chicago in June 2018 revealed that almost half the patients had a very substantial shrinkage in their tumour, and patients lived longer than would be expected for chemotherapy alone.
Professor Anna Nowak who is also Pro Vice Chancellor (Health and Medical Research) at UWA and Director at UWA’s National Centre for Asbestos Related Diseases, said the results were ‘incredibly exciting and meaningful’.
“I put many of my own patients on the DREAM trial so I’ve seen people have remarkable responses to the treatment, I’ve seen dramatic reductions in tumour volumes that were more frequent and more profound than I was used to seeing in mesothelioma. Just watching people’s quality of life improve and their symptoms reduce and looking at the benefits that we can see on their scans – it was incredibly fulfilling.”
The skilled researcher and oncologist has also been instrumental in establishing a cross-disciplinary state-wide Western Australian neuro-oncology service and is the immediate past Chair of the national cooperative trials group for neuro oncology (COGNO).
She also previously co-chaired the AGOG tissue banking project where she led a team that collected tumour and blood biospecimens and clinical data from over 1000 patients with glioma. This biospecimen bank is now available as a research resource.
Professor Nowak’s research in high grade glioma focuses on active participation in clinical trials and collaboration on psychosocial and supportive care research questions. But of her early involvement in the field Professor Nowak says that came about by chance when the anti cancer drug temozolomide came into use in the mid 2000’s
“It was really the first time that medical oncologists were becoming involved in brain cancer care. When I returned to a job in Western Australia I was the newest recruit and given the role of working in brain cancer.”
The role was thought to be ‘a small job’ at the time, she adds, but with more effective treatments fast becoming available and more patients on the new regimens, it quickly became clear that there were gaps in care, she recalled.
“I really started applying not so much my scientific and PhD research but some of the postdoctoral research that I’d carried out in quality of life and clinical trials, particularly the quality of life work into patients with brain tumour, to understand what their unique needs may be and what their gaps in care may be.”
That work led to the establishment of the multidisciplinary neuro-oncology care unit at Charles Gairdner Hospital where Professor Nowak currently works.
“I’m really proud of the patient care we deliver in our neuro-oncology unit at Charles Gairdner Hospital. We now have three consultant medical oncologists, two nurses and social workers, occupational therapists and physiotherapists. We truly are a multi-disciplinary team.”
Reflecting on what inspires her approach to leadership and collaboration, Professor Nowak says that comes from a ‘deep seated need to be doing good’.
“I just try to take a perspective that is outside of myself and always think if I was the other person how would I like these interactions to go? I make sure I give people the time that they need, the information that they need in a way that they want. I approach my interactions with patients that way but it also works well with students and mentees. I would say my leadership style is ‘servant leader’ – I spend time looking at how I can be of value to others to create more good in the world.
Looking ahead at what’s next in mesothelioma research Professor Nowak says she’s looking forward to the upcoming randomised clinical trials of surgery in this disease.
“I truly have no idea what the answer will be but I think it’s really important that our British colleagues are asking the question and hopefully will get a robust answer about whether there is a role for surgery in mesothelioma.”
The acclaimed investigator also wants to delve into which patients stand to benefit most from the new therapies.
“We need to take the results from the current clinical trials like combination immunotherapy and combination chemo-immunotherapy and we need to use translational information and data bioinformatics to unravel in more detail which of our patients will benefit from the different approaches that are available.
Once we know who might benefit and we know who doesn’t, we might have an opportunity to push lack of benefit through to benefit from understanding the biology. So for every clinical trial we do we have to be really rigorous about interrogating the translational science opportunity that comes along with that.”