Daily highlight in non-metastatic NSCLC

Reported by Dr Mariana Brandao, Institute Jules Bordet, Brussels

Dr Mariana Brandao, a medical oncologist at the Clinic of Thoracic Oncology at the Institute Jules Bordet in Brussels, provided insights into various mini-oral presentations focusing on non-metastatic NSCLC.

In the context of resectable NSCLC, the CheckMate 816 study examined neoadjuvant chemotherapy with nivolumab immunotherapy, followed by surgery. Notably, the regimen demonstrated impressive EFS results and has gained approval in Europe for patients with PD-L1 tumour expression, with reimbursement in Belgium. The 3-year results, categorised by tumour PD-L1 expression, were presented at ESMO. Patients with PD-L1 expression showed a 25% difference in EFS and a 20% difference in OS, justifying the treatment in this population. While the benefit was more minor in PD-L1 negative patients, there was still an 11% difference in OS, considered clinically significant though not statistically significant. While the chemo-IO combination cannot currently be used in this population, alternative strategies, such as double IO escalation or other compounds, may hold promise.

Another approach in the resectable NSCLC setting is the perioperative strategy, which involves chemo plus immunotherapy before surgery, followed by adjuvant immunotherapy for one year. Several trials, including the AEGEAN trial, have explored this approach. However, evaluating clinical benefit is complicated as the radiological response does not consistently correlate with pathological complete response. The use of biomarkers, like ctDNA clearance, has been considered. In the AGEAN subanalysis, patients with positive ctDNA at diagnosis had a higher chance of achieving pathological complete response, though the positive predictive value was 50%. Hence, it’s not yet a reliable predictive biomarker for clinical practice.

For patients with unresectable stage III NSCLC, the standard of care involves chemoradiotherapy followed by adjuvant durvalumab, based on the PACIFIC trial. However, in many European countries, including Belgium, some patients receive sequential rather than concurrent chemoradiotherapy. Fortunately, reimbursement for adjuvant durvalumab is available in Belgium for these patients. The PACIFIC 6 trial was designed for patients who received sequential chemoradiotherapy and demonstrated safety and efficacy with low treatment-related adverse events, including a median PFS of 13 months and a median OS of 39 months.

Patients with unresectable stage III NSCLC, ineligible for chemotherapy, currently receive radiotherapy alone, associated with poor survival rates. The DUART study explored the safety and tolerability of adjuvant durvalumab for one year following radiotherapy in two cohorts: those receiving standard radiotherapy and those undergoing palliative radiotherapy. The results showed no new safety signals, and notably, the median progression-free survival was eight months, with a median overall survival of 16 months. While these outcomes are lower than those seen with chemoradiotherapy followed by durvalumab, they provide valuable treatment options for frail patients with comorbidities who cannot receive platinum-based chemotherapy, potentially expanding the use of durvalumab in the future.

References:

Mariano Provencio Pulla – Neoadjuvant nivolumab (N) + chemotherapy (C) in the phase 3 CheckMate 816 study: 3-y results by tumor PD-L1 expression. ESMO23 – LBA57

Martin Reck – Associations of ctDNA clearance and pathological response with neoadjuvant treatment in patients with resectable NSCLC from the phase 3 AEGEAN trial. ESMO23 – LBA59

Marina Garassino – Durvalumab (durva) after sequential chemoradiotherapy (CRT) in patients (pts) with unresectable Stage III NSCLC: Final analysis from PACIFIC-6. ESMO23 – LBA61

Andrea Riccardo Filippi – Durvalumab after radiotherapy (RT) in patients with unresectable stage III NSCLC ineligible for chemotherapy (CT): Primary results from the DUART study. ESMO23 – LBA62