Dr John Conibear speaks to Kathy Oxtoby about the changing treatment landscape of non-small cell
lung cancer, durvalumab’s latest approval by the MHRA for the resectable form, and his hopes for the future management of the condition.
The UK has one of the worst five-year survival rates for lung cancer in Europe, and new treatment options are urgently needed to offer patients a better chance of long-term survival.
This July, the Medicines and Healthcare products Regulatory Agency (MHRA) granted marketing authorisation in Great Britain for durvalumab (brand name Imfinzi) for the treatment of adults with resectable non-small cell lung cancer (rNSCLC).
This anti-programmed death ligand 1 monoclonal antibody is now indicated in combination with platinum-based chemotherapy as a neoadjuvant treatment before surgery, followed by durvalumab as adjuvant monotherapy after surgery, in those who have no known epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements or aberrations.
This joins durvalumab’s existing indication for the treatment of adult patients with locally advanced, unresectable NSCLC, meaning the drug is now approved in Great Britain for both resectable and unresectable forms.
Durvalumab is ‘promising step forward’
The latest approval from the MHRA is based on positive data from the AEGEAN Phase III trial in rNSCLC, which showed that durvalumab-based treatment before and after surgery reduced the risk of recurrence, progression events or death by 32% versus neoadjuvant chemotherapy alone.
Dr John Conibear is a consultant clinical oncologist and clinical director for thoracic oncology at Barts Cancer Centre, London, and oncology lead for the National Lung Cancer Audit (NLCA). He says the AEGEAN Phase III trial represents ‘a promising step forward in the management of patients with resectable lung cancer’.
‘The trial demonstrates that the combination of immunotherapy with traditional chemotherapy, in both the neoadjuvant and the adjuvant setting improves pathological response rates and disease-free survival,’ he says. ‘That could potentially lead to better long-term outcomes and increased survival rates for these resectable patients.’
The use of durvalumab in combination with chemotherapy for treating rNSCLC is still pending approval from the National Institute of Health and Care Excellence (NICE) and is currently not recommended by the organisation in its initial draft guidance, which has been out for consultation and is now being considered by the committee.
Dr Conibear says the results of the trial show that ‘the addition of this drug does seem to reduce the relapse of patients with lung cancer in this resectable setting, and it increases the rates of complete responses’. For him, there is ‘clearly synergism between chemotherapy and immunotherapy in this setting’, and Dr Conibear is in favour of durvalumab being available on the NHS for routine use in this patient group.
‘From a clinician’s point of view, I want to do what’s best for my patients, and it’s a shame if durvalumab is considered unsuitable on the basis of financial availability rather than clinical benefit,’ he says.
Whether NICE changes its current stance, only time will tell.
A dynamic field
Dr Conibear’s insight into the importance and value of durvalumab for lung cancer patients comes from more than 20 years of working in oncology, including thoracic oncology.
It was during the early part of his training as a junior doctor in 2003 that he chose this specialism. ‘As a medical specialty, oncology is dynamic, and always seems to evolve, because of the nature of the treatment we can offer patients,’ says Dr Conibear.
Patients with cancer require ‘a compassionate and thoughtful approach to their care’, he says. ‘Oncology fuses both the science and compassion of medical care into one specialty, which I find attractive.’
His particular interest in thoracic oncology was sparked towards the end of his oncology training. ‘I was involved in clinical trials looking at improving outcomes in patients with locally advanced lung cancer, and through that I began to appreciate the complexities in diagnosing and treating lung cancers.’
Treatment landscape of NSCLC
During the last decade since Dr Conibear became a consultant, the treatment landscape of NSCLC, in both the UK and Europe, has evolved significantly. ‘That’s been driven by advancements in targeted therapies, immunotherapy and the more personalised approach to patient care,’ he says.
Understanding the molecular biology of NSCLC has made a huge difference, with clinicians ‘now able to identify specific gene mutations, which allows us to use specific targeted therapies, and these offer better efficacy and often fewer side effects compared to traditional chemotherapy’.
Then there is the advent and evolution of immunotherapy. ‘This has revolutionised NSCLC treatment, both in the early, locally advanced and metastatic settings. This has become the standard of care for many patients with NSCLC, and led to significant improvements in survival rates,’ he says.
‘Through these advances in treatment, and the combination of these treatments, whereby you create a personalised multimodality approach, we’ve seen improvements in patient survival. We see patients not only cured of their disease, but also living with their disease for much longer than we ever saw in the past,’ he adds.
However, in the UK, what is clear from ongoing data analysis – such as the National Lung Cancer Audit’s ‘State of the Nation 2024’ report – is that much more needs to be, and potentially can be, done. ‘There is still an unmet need when it comes to treating patients with both early and advanced lung cancer in regard to the number of patients who don’t seem to be receiving optimal cancer-driven care’, Dr Conibear says.
‘We’re trying to explore the reasons behind that – the potential biases and inequalities that are causing these differences to occur, both within regions of the UK, and also the UK compared to our European brothers and sisters.’
Durvalumab’s evolving place in NSCLC
The AEGEAN Phase III trial is evolving the treatment landscape further, says Dr Conibear.
Durvalumab has become ‘a cornerstone in the management of unresectable locally advanced NSCLC’, and ‘the AEGEAN trial potentially, as the data matures, could reveal durvalumab to have a similar role in resectable patients,’ he suggests.
Until now, treatment has been focused on just the neoadjuvant use of chemoimmunotherapy in resectable patients before they have surgery.
‘What this trial demonstrates is expanding that treatment beyond surgery, so that patients then come back after surgery to receive further immunotherapy,’ Dr Conibear says. ‘Essentially, we’re intensifying the patient’s treatment to see an improved long-term outcome – we hope.’
Dr Conibear would like durvalumab to ‘translate into a meaningful improvement in long-term survival and push the bar higher in what we consider to be standard outcomes for these patients’, and he believes there is certainly potential for this to happen.
Sharing knowledge and insight
While clinicians and multidisciplinary teams (MDTs) working in lung cancer care understand the role of durvalumab in treating patients with unresectable lung cancer, Dr Conibear says ‘there is a knowledge gap now for people in those teams to understand the role of durvalumab in that resectable patient group, following the results of the AEGEAN trial’.
If NICE’s final ruling is in favour of durvalumab for treating rNSCLC ‘then there will be a need to target education towards these clinicians to expand that knowledge base’, he says. This could include educational initiatives such as workshops, seminars and webinars focused on the role of durvalumab in non-small cell lung cancers. And guidelines and protocols will need to be updated to reflect these evolutions of approaches to patient care.
Ongoing professional development should be encouraged, ensuring that the MDT attends training sessions to stay up to date with the latest practices and treatment recommendations, he says.
As patients are becoming increasingly complex in terms of the personalised approach required for their care, Dr Conibear sees a greater need for case discussions and the sharing of ‘knowledge and experience between multidisciplinary team meetings’. There is also a role for direct peer-to-peer learning and encouraging experienced oncologists to share insights through mentorship programmes or peer-led discussions, he adds.
‘And what mustn’t be forgotten is the dissemination of information to patients, arming them with the knowledge of what’s available, and what’s potentially suitable for them so they can also be an advocate for their own care,’ he says. ‘Patient education and advocacy are also important to dispel the limitations on what we offer our patients.’
Future management of NSCLC
As to further developments in the management of NSCLC beyond durvalumab, attention is turning to new mutations, which Dr Conibear says are ‘potentially druggable’ and ‘could form further aspects of that personalised approach to patient care in the resectable and unresectable lung cancer setting’.
Then there are advances in diagnostics, in particular liquid biopsies – the ability to collect and analyse circulating tumour DNA and circulating tumour cells. ‘We can use these measures to understand resistance patterns to treatment so that we potentially have a more dynamic and adaptive treatment plan that we can offer our patients,’ he says.
‘We can see at a microscopic level whether the treatment is working or not, so that we can make clinical management decisions more quickly than we have done historically.’
Dr Conibear also highlights the integration of artificial intelligence and machine learning into clinical practice. ‘These tools are capable of analysing large data sets, including imaging, genomic data and clinical data,’ he says. ‘It seems with the right algorithms you’re capable of predicting patient outcomes and responses to therapy, and possibly even unwanted adverse events or effects more accurately. This technology could help us to enhance this personalised treatment approach to patients.’
And with the AEGEAN trial showing the benefit of immunotherapy and chemotherapy before, and now also after surgery, ‘it’s demonstrating, again, the importance of a multimodality approach to these patients’, Dr Conibear says. ‘As we move on, we’ll see the potential of other treatments added into this approach.’
It’s no secret that Dr Conibear would like durvalumab to be available to real-world rNSCLC patients who are eligible for the treatment. ‘And it would be great to not see it as the final step, but a stepping stone in terms of improving things further for these patients,’ he says.
‘Ultimately, I hope durvalumab plays a pivotal role in advancing lung cancer treatment, thereby contributing to higher survival rates, improved quality of life and pushing the bar higher on the idea of a personalised approach to these patients’ care. I’m optimistic we’ll see that.’
