Proffered paper session: non-metastatic lung cancer

In this video, Prof Dr Johan Vansteenkiste, a thoracic oncologist at the University Hospitals Leuven, discusses a selection of abstracts presented during the proffered paper session on non-metastatic lung cancer at ESMO 2024.

The CCTG BR-31 trial, presented at ESMO by Dr Goss, examined adjuvant durvalumab for resected NSCLC in contrast to other well-established immunotherapy trials, such as Impower010 with atezolizumab and Keynote-091-PEARLES with pembrolizumab. Atezolizumab has been approved for PD-L1 high tumours, while pembrolizumab is used for all PD-L1 expressing tumours. The BR-31 trial, an academic study conducted primarily in Canada, France, and Japan, focused on patients with PD-L1 expression over 25%, excluding those with ALK or EGFR mutations. The trial’s primary endpoint was DFS, with some initial indication of durvalumab providing a small improvement in median DFS—70 months versus 60 months for the placebo. However, the study ultimately failed to demonstrate statistically significant benefits, with a hazard ratio of 0.93. This non-significant result held true across several analyses, including PD-L1-positive patients (over 1%) and the broader “all-comers” population.

One unexpected observation in the trial was that, after two to three years, the placebo arm outperformed expectations, complicating the interpretation of the data and possibly contributing to the lack of significant difference in outcomes between the durvalumab and placebo groups. This unexpected benefit in the placebo arm was discussed, with one hypothesis offered by Dr Goss suggesting that the patients’ treatment in high-level academic centers, with strict adherence to surgical guidelines, including thorough lymph node dissections, may have influenced the results. The hypothesis is that the rigorous surgical procedures left fewer lymph nodes behind, limiting the potential for immunotherapy like durvalumab to work as effectively post-surgery. While this explanation is intriguing, it remains a hypothesis requiring further investigation. The trial’s unexpected negative outcome is seen as part of the growing evidence supporting perioperative approaches, rather than strictly adjuvant therapy, for patients with resected NSCLC. Particularly in those with lymph node-positive disease, the trend appears to be moving toward perioperative treatments, which combine neoadjuvant and adjuvant therapies to enhance overall patient outcomes potentially.

The ADRIATIC trial, presented at ESMO 2024, marks a significant step forward in the treatment of non-metastatic SCLC. For over 20 years, chemoradiotherapy has been the standard of care, with no major breakthroughs during that time. However, the ADRIATIC trial introduces durvalumab as a consolidation therapy following concurrent chemoradiotherapy, potentially changing the landscape of SCLC treatment. The trial’s initial results were presented at ASCO 2024, showing a clear benefit in overall survival for patients treated with durvalumab compared to placebo. The hazard ratio for overall survival was 0.73, with a median survival of 57 months for durvalumab versus 33 months for placebo. At the three-year mark, 57% of patients on durvalumab were still alive compared to 47% in the placebo group, showing a 10% increase in survival. This result is quite similar to what was observed in the Pacific trial, which evaluated durvalumab in a similar setting for non-small cell lung cancer.

At ESMO 2024, Dr Senan presented subgroup analyses from the ADRIATIC trial, exploring whether different treatment approaches — such as the type of chemotherapy (carboplatin or cisplatin), radiotherapy schedules, or the use of prophylactic cranial irradiation — influenced the benefit of durvalumab. The effect of durvalumab was consistent across most subgroups, with one notable exception: patients who received carboplatin appeared to derive slightly more benefit from durvalumab than those who received cisplatin, despite cisplatin being the long-standing standard. However, this finding is not expected to change clinical practice as the group receiving carboplatin was small, and cisplatin will likely remain the standard chemotherapy agent in this setting. The safety profile of durvalumab in the ADRIATIC trial was acceptable, with the expected range of immune-related adverse events, but no new safety signals emerged compared to what has been seen in non-small cell lung cancer trials. Physicians are now well-versed in managing immunotherapy-related side effects. Overall, the ADRIATIC trial offers strong evidence in favour of durvalumab as a consolidation therapy for one year following concurrent chemoradiotherapy in non-metastatic SCLC. This positive outcome is expected to be practice-changing soon.

The trial’s success contrasts with the results from other studies, like the CCTG BR-31 trial in non-small cell lung cancer, which was negative for adjuvant durvalumab after resection. Further research is needed to understand why adjuvant immunotherapy works in some settings and not in others.