Managing toxicities of concurrent chemotherapy and radiation (CRT), assessing the status of disease during treatment, and timing the initiation of consolidation immunotherapy are some of the challenges facing oncologists managing stage III unresectable non-small cell lung cancer patients in both metro and regional settings.
In a webinar chaired by Associate Professor Nick Pavlakis (view webinar here), from the Royal North Shore Hospital, and hosted by AstraZeneca Oncology, a panel of lung cancer experts explore some of these issues through a case-study based discussion.
The role of immune checkpoint inhibitors in Stage III NSCLC
Definitive concurrent chemotherapy and radiation (CRT) is standard treatment for Stage III unresectable locally advanced NSCLC.1 Yet, despite its curative intent, the 5-year overall survival rate is around 15 – 25%.2 Consolidation after CRT with the immune checkpoint inhibitor durvalumab (Imfinzi®) has been shown to significantly improve progression-free survival,2 and is now available on the PBS for the treatment of patients with NSCLC who have not progressed on chemoradiation.3
The following three case studies provide an avenue for exploring perspectives on promoting optimal patient recovery after CRT, the most appropriate timing of durvalumab consolidation therapy, and challenges treating patients with lung cancer in regional centres.
Case 1 – A multidisciplinary approach is the key to managing CRT toxicities
Radiation oncologist Doctor Fiona Hegi-Johnson from Peter MacCallum Cancer Centre in Melbourne and medical oncologist Doctor Sagun Parakh from Austin Health presented a case that emphasised the importance of a multidisciplinary approach to CRT toxicity management.
A 75-year old ex-smoker diagnosed with adenocarcinoma (PDL1 5%, mutation negative) was treated with definitive CRT. He developed shortness of breath and presented to ED, where a CT scan showed findings consistent with radiation pneumonitis. This was treated with prednisolone and then tapered down slowly over 6 weeks. After cessation of prednisolone, the patient received durvalumab for 12 months, and his most recent CT scan showed no tumour recurrence.
Doctor Hegi-Johnson, noted that regular multidisciplinary communication, clear documentation, and proactive management is essential when managing CRT toxicities. “At the end of this treatment, we want the patient to be fit and well enough to get whatever they need next,” she noted. In addition to discussing the detection and management of radiation-induced pneumonitis, she described the multidisciplinary approach to CRT-induced oesophagitis, which she explained can impact on nutritional and performance status, and subsequently delay the commencement of immunotherapy.
The benefits of supervised pulmonary rehabilitation were also discussed, including the importance of an individualised rehabilitation prescription and exercise training. “The role of pulmonary rehabilitation is well established in locally-advanced and in surgical patients,“ explained Dr Parakh.
Case 2 – The value of scans and optimal timing of durvalumab therapy
Doctor Dasantha Jayamanne, a radiation oncologist at Northern Sydney Cancer Centre, presented a case that focused discussion on timing of CT scans and commencement of consolidation immunotherapy.
A 53-year old female presenting with a 3-month history of dry cough, mild dyspnoea, and haemoptysis was found on biopsy to have an adenocarcinoma (T2N2MO; stage IIIA; PD-L1 expression 30%). The Sonic contextual genomics report showed L858R Exon 21 EGFR mutation, with no T790M mutation. The tumour was found to be rapidly-growing upon re-staging CT-PET four weeks later. The panel discussed management options during the progress of the case, reflecting the complicated algorithm for patients presenting with Stage III NSCLC.
The timing for initiation of durvalumab following CRT was discussed, with the experts agreeing that initiation is only appropriate after resolution of CRT toxicity, particularly respiratory symptoms. Associate Professor Pavlakis explained his tendency to commence durvalumab four to six weeks after CRT. He also opts to undertake a CT scan before initiating durvalumab: “I like to know if there is any subclinical disease…if the patient is well and asymptomatic, the scan is just giving you a baseline,” he said.
Case 3 – Treatment of Stage III unresectable NSCLC in a regional setting
Doctor Rob Zielinski, head of Central West Cancer Centre, in Orange, treats a range of cancers in his regional centre. His case highlighted the challenges in the regional setting, including the limited availability of diagnostic services, particularly CT-guided biopsy. “We do lack some services…These things take time to organise, and the diagnostic window tends to be longer in a regional context than in a metro centre,” he said.
An active 70-year-old with COPD who presented with chest pain and subsequently diagnosed with Stage IIIA large cell NSCLC (PD-L1<1%) was admitted to hospital three times during CRT for dyspnoea, pain crisis, and chest pain. At day 60, he was reviewed by his GP for a mild change in breathlessness and given antibiotics. Dr Zielinski pointed out the real world considerations of situations where steroids and antibiotics have been prescribed – in this case to help manage COPD exacerbations and infection – and their potential impact on the effectiveness of immunotherapy.
Rural and regional patients also often face the inconvenience of travelling long distances for treatment, Dr Zielinksi noted. Other factors that impact on care include the limited chemotherapy weekend services, lack of a dedicated lung cancer nurse, and limited access to allied health support such as exercise therapy.
Cases illustrate the heterogeneity of Stage III disease
Associate Professor Pavalakis thanked AstraZeneca for providing the opportunity for the faculty to discuss post-CRT treatment in Stage III unresectable NSCLC. He noted that the breadth of the presented cases reflected the complex nature of treating Stage III disease. “There is no one-size-fits-all, and these case examples have highlighted the variation,” he said.
- Cheema PK et al. Perspectives on treatment advances for stage III locally advanced unresectable non-small-cell lung cancer. Curr Oncol 2019;26(1):37–42. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380636/
- Antonia SJ et al. Durvalumab after chemoradiotherapy in Stage III non–small-cell lung cancer. NEJM 377;20:1919–1929. https://www.nejm.org/doi/full/10.1056/NEJMoa1709937
- Pharmaceutical Benefits Scheme Authority Listing: Durvalumab https://www.health.gov.au/ministers/the-hon-greg-hunt-mp/media/new-hope-for-lung-cancer-patients-with-ground-breaking-treatment-option-to-be-listed-on-the-pbs