Highlights on lung cancer 2

Dr Dieter Stevens, a thoracic oncologist at University Hospitals Gent in Belgium, shares key findings from ASCO2024 on advanced or metastatic NSCLC patients with rare oncogenic alterations.

The WU-KONG1 study is a phase 2 trial examining the efficacy of sunvozertinib in patients with EGFR exon 20 insertion mutations, which constitute only 2% of all NSCLC cases. Sunvozertinib was administered orally at either 200 mg or 300 mg daily to 184 patients who had all been pretreated with at least platinum-based chemotherapy. The primary endpoint ORR was 45%, with a disease control rate of about 90%. Sunvozertinib was well tolerated, with diarrhoea, skin rash, and elevated creatinine kinase as the most frequent adverse events. Its efficacy is being further evaluated in an ongoing global phase 3 randomized trial.

The CHRYSALIS-2 trial focuses on atypical EGFR-mutated advanced NSCLC patients, assessing the combination of amivantamab and lazertinib in multiple cohorts. Amivantamab, a bispecific antibody against EGFR and MET, combined with lazertinib, a third-generation EGFR TKI with good brain activity, has shown remarkable results in common EGFR mutations. Among the 105 enrolled patients, the primary endpoint ORR was 51%. Notably, treatment-naive patients demonstrated a median PFS of 19.5 months, the longest to date in this specific population. Adverse events were well-known and manageable.

In the phase, Ia/Ib Beamion LUNG-1 trial, the anti-tumour activity of zongertinib, a HER2-specific TKI, was assessed in patients with advanced solid tumours harboring HER2 gene alterations. In the phase Ib part, 42 heavily pretreated HER2 mutant NSCLC patients were included, showing an ORR of 74%, significantly higher than with T-DXd and other HER2-directed therapies. This outcome, combined with overall good tolerability, positions zongertinib as a potential new treatment option, pending further evaluation in an ongoing phase 3 randomized trial.

The efficacy and safety of erdafitinib in patients with solid tumours and FGFR alterations were investigated in the RAGNAR trial, a pan-tumour phase 2 trial. Erdafitinib, an oral TKI targeting FGFR gene alterations, mutations, and fusions, was evaluated in 23 NSCLC patients, resulting in an ORR of 26% across both squamous and non-squamous histologies. These findings are encouraging given the treatment difficulties and limited systemic options available.

The phase 2 TRUST-I study evaluates the efficacy and safety of taletrectinib in patients with ROS1+ NSCLC. Taletrectinib, a next-generation ROS1-TKI with excellent CNS activity and effectiveness against G2032-resistant mutations, is the largest study to date, including 173 patients. The primary endpoint ORR, assessed by blinded independent review, was 91% in treatment-naive patients and 51% in those pretreated with crizotinib. Median PFS was not reached in treatment-naive patients and was 7.6 months in pretreated patients. The most common side effects were elevation of liver enzymes and diarrhoea, both manageable, introducing taletrectinib as a promising new treatment option.