Daily highlight in non-metastatic NSCLC & other thoracic malignancies

In the field of non-metastatic non-small cell lung cancer (NSCLC), Professor Lore Decoster, a medical oncologist at UZ Brussels, made a selection of abstracts presented during the proffered session on non-metastatic, non-small cell lung cancer (NSCLC).

An exploratory analysis of the third arm of the CHECKMATE 816 study revealed that the combination of nivolumab and ipilimumab demonstrated a significant improvement in event-free survival and pathological complete remission compared to chemotherapy alone. Patients appear to derive long-term benefits from this combination therapy. However, a subset of patients did not proceed to surgery due to disease progression, and this proportion was higher than observed in the chemotherapy-alone arm.

The KEYNOTE 671 trial is a randomised, double-blind, phase 3 trial evaluating perioperative pembrolizumab in early-stage NSCLC patients. At ESMO 2023, this study reported impressive overall survival results, with a statistically significant improvement and a hazard ratio of 0.72. At the three-year mark, the survival benefit amounted to approximately 7%. Prof. Decoster emphasised the importance of patient selection since all participants in this trial received cisplatin-based neoadjuvant chemotherapy, which may not be applicable to all real-world clinical cases.

Two radiotherapy trials were briefly discussed. The first, a Chinese trial, investigated neoadjuvant radiotherapy followed by a combination of chemotherapy and immunotherapy, demonstrating remarkable rates of pathological complete response. However, this approach also led to increased toxicity, with about one-third of patients experiencing grade 3 or greater adverse events. The second trial, a French intergroup study, assessed the feasibility and safety of delivering a radiation boost up to 74 Gy based on early lung tumour response to on-treatment FDG-PET/CT (42 Gy) in inoperable stage III NSCLC patients. This approach improved event-free survival, and the toxicity was manageable, with no observed increase in acute or chronic toxicities.

Finally, two interesting abstracts were discussed. The first pertained to the RELEVENT phase II trial, an Italian phase II single-arm open-label study, where ramucirumab was added to chemotherapy for untreated metastatic thymic carcinoma. The trial was stopped after enrolling 35 patients due to the rarity of the disease, but the results support the use of this combination as a first-line treatment for thymic carcinoma. The second study, the phase II DeLLphi-301 trial, evaluated tarlatamab, a bispecific T-cell engager targeting delta-like ligand 3 on SCLC cells and CD3 on T cells. This therapy demonstrated remarkable antitumor activity in heavily pretreated SCLC patients, with durable responses and promising survival outcomes.