ELCC 2024 Daily highlight 2

Prof Mariana Brandão, medical oncologist at Institute Jules Bordet, Hôpital Universitaire de Bruxelles shares her insights from the proffered paper session.

Updated results from the FLAURA-2 trial were presented, including PFS 2 and OS. The combination of platinum-pemetrexed chemotherapy alongside osimertinib among treatment-naïve patients exhibiting EGFR-positive tumours showcased superior efficacy compared to osimertinib monotherapy, particularly evident in terms of PFS-2. Concerning OS, an evolving divergence is observable, with a notable survival advantage seen in the combination arm at the 2-year mark. However, it is imperative to note that the dataset is still evolving, warranting further accrual to ascertain any discernible disparities in OS. Remarkably, the observed benefit was more pronounced in patients presenting with brain metastases. This could potentially be attributed to a considerable proportion of these patients receiving chemotherapy as second-line therapy, including those who had received it as first-line treatment.

Surgery outcomes of the RATIONALE-315 trial were reported evaluating perioperative tislelizumab or placebo with neoadjuvant chemotherapy in patients with resectable NSCLC. Within the tislelizumab arm, there was a notable reduction in the incidence of pneumectomies. The R0 resection rate exhibited similarity across both arms, as did the duration between systemic therapy and surgery. Furthermore, there was no significant discrepancy observed in post-surgical complications between the two arms. During the ensuing discussion, Dr Jonathan Spicer raised an important point regarding the definition of post-surgical complications. He suggested that the terminology used, largely derived from the CTCAE and predominantly conceptualized by medical oncologists, might not fully encapsulate pertinent surgical complications such as bronchopulmonary fistulas and malignant pleural mesothelioma.

In the PACIFIC-2 trial, durvalumab was administered concurrently with chemotherapy and radiotherapy, constituting the experimental arm, while the control arm received only chemoradiotherapy followed by placebo due to durvalumab not yet being approved at the time of the trial initiation. Notably, there was no discernible difference in PFS between the two arms during chemoradiotherapy, with overlapping survival curves observed. However, post-chemoradiotherapy, a separation of survival curves became evident. A plausible explanation for this disparity lies in patient selection; the PACIFIC regimen allows for the identification of patients who respond favourably to chemoradiotherapy. Conversely, in the PACIFIC-2 trial, all patients received this regimen, including those with aggressive disease phenotypes less likely to respond to any therapeutic intervention, including durvalumab. A pivotal consideration in the trial was the presence of EGFR mutations, which were only determined in half of the patient population. Subgroup analyses revealed a greater benefit among European patients compared to those in Asia and Latin America. This discrepancy may stem from a higher prevalence of EGFR mutant tumours in the Asian population, rendering them less responsive to durvalumab and potentially diluting its efficacy. Fortunately, concerns regarding toxicity were not pronounced, with manageable adverse events observed. Despite being a negative trial in terms of primary endpoints, the PACIFIC-2 trial provided valuable insights favouring the PACIFIC regimen, advocating for sequential administration of chemoradiotherapy followed by durvalumab.

The 7-year follow-up of the CONVERT study, which compared once-daily radiotherapy (66 Gy) versus twice-daily radiotherapy (45 Gy) combined with platinum-based chemotherapy in patients with limited-stage SCLC revealed no superiority of the once-daily regimen. Despite initial expectations, this regimen exhibited a slightly worse toxicity profile, primarily characterized by increased incidence of esophagitis. However, regarding other significant toxicities, the disparity between the two regimens was not substantial.