Presidential symposium 2

Prof Dr Christophe Dooms, thoracic oncologist at UZ Leuven summarises the key findings from the second presidential symposium at WCLC. 

An exploratory eight-year analysis of the phase III ADAURA trial showed a sustained OS benefit with three years of adjuvant osimertinib after complete resection of EGFR-mutated stage IB–IIIA NSCLC. In the primary stage II–IIIA population, eight-year OS was 74% with osimertinib versus 58% with placebo. The corresponding rates in the overall stage IB–IIIA population were 79% and 64%. These findings extend the survival benefit reported in the earlier final analysis, although the presentation did not resolve questions about patterns of recurrence or the efficacy of osimertinib retreatment after relapse.

The final OS analysis of the phase III PAPILLON trial evaluated first-line amivantamab plus carboplatin–pemetrexed in advanced NSCLC with an EGFR Ex20ins. Median OS was 34.3 months with the combination and 27.9 months with chemotherapy alone, a numerical difference that did not reach statistical significance. Among patients in the chemotherapy arm who discontinued treatment because of progression, 76% subsequently received amivantamab. This crossover may have reduced the observed difference between the randomised groups; a prespecified crossover-adjusted analysis favoured the combination.

The phase III REZILIENT 3 trial also addressed first-line treatment of advanced EGFR Ex20ins-positive NSCLC. Adding zipalertinib to platinum–pemetrexed significantly improved median PFS from 8.5 to 14.5 months. Overall survival data remain immature. The efficacy gain must be considered alongside toxicity: grade ≥3 adverse events occurred in 87.1% of patients receiving the combination versus 54.4% receiving chemotherapy alone, predominantly reflecting haematological events.

In advanced NSCLC harboring HER2 Ex19 or Ex20 mutations, the phase III DESTINY-Lung04 trial compared first-line T-DXd with pembrolizumab plus platinum-based chemotherapy. Median PFS was 14.3 vs. 8.3 months, respectively (HR 0.63; p<0.0001). An OS benefit has not been demonstrated: median OS was 29.3 vs. 33.1 months, with interpretation complicated by differences in subsequent treatment. Drug-related ILD or pneumonitis occurred in 20.8% of patients receiving T-DXd vs. 2.3% in the comparator arm.

Finally, the single-arm phase I/II ARROS-1 study reported an objective response rate of 94% among 94 evaluable patients with advanced ROS1-positive NSCLC who had not previously received a ROS1 TKI. All 10 patients evaluable for intracranial response responded, including seven complete intracranial responses. These results suggest substantial systemic and central nervous system activity with zidesamtinib, while its longer-term benefit requires further follow-up.