Dr Girard on the Development of ADCs in Patients With NSCLC

Nicholas Girard, MD, PhD, professor, respiratory medicine, Versailles Saint Quentin University, head, the Curie-Montsouris Thorax Institute, the Institut Curie, discusses the evolving role of antibody-drug conjugates (ADCs) in the treatment of patients with non–small cell lung cancer (NSCLC), highlighting data from the phase 3 TROPION-Lung01 study (NCT04656652).

At the 2023 ESMO Congress, Girard highlighted developments with the use of ADCs derived from ongoing clinical trials that were read out at the conference. These developments included the examination of datopotamab deruxtecan (Dato-DXd; DS-1062a) vs docetaxel in pretreated patients with advanced or metastatic disease, as evaluated in the TROPION-Lung01 study.

At the meeting, investigators shared that the Trop2-directed ADC Dato-DXd exhibited a significant enhancement in progression-free survival (PFS) compared with docetaxel in patients with advanced or metastatic NSCLC. However, it's important to note that patients with squamous histology did not derive the same benefit from this treatment. Within the intention-to-treat population, patients who received Dato-DXd (n = 299) achieved a median PFS of 4.4 months (95% CI, 4.2-5.6), whereas those in the docetaxel arm (n = 305) experienced a median PFS of 3.7 months (95% CI, 2.9-4.2), translating to a 25% reduction in the risk of progression or death (HR, 0.75; 95% CI, 0.62-0.91; P = .004). Although a PFS benefit was observed with Dato-DXd in patients with nonsquamous histology (HR, 0.63), those with squamous histology did not experience a benefit (HR, 1.38).

In the realm of lung cancer, multiple agents with various targets, including Trop2, are under development, Girard begins. Notably, the benchmark for comparison is docetaxel, a second-line treatment option, he states. The efficacy of docetaxel is limited, and any treatment approach that can enhance patient outcomes warrants careful consideration, Girard explains.

The data from the TROPION-Lung01 trial demonstrate a gradual but significant improvement in PFS with Dato-DXd vs docetaxel, Girard expands. However, a more thorough assessment of these data may be required to fully grasp the extent of this benefit. Furthermore, the study outcomes reveal variations among different patient subsets based on histological and molecular characteristics, he explains. This underscores the need for a deeper understanding of which patients stand to gain the most from this second-line treatment opportunity, Girard says.

Currently, extensive investigations are ongoing in the first-line NSCLC setting, where ADCs are being combined with immune checkpoint inhibitors and platinum-based chemotherapy, he continues. This represents a step forward in metastatic NSCLC research, as investigators aim to enhance long-term survival outcomes, he says. Although there have been strides with immune checkpoint inhibitors in this population, the focus now is on increasing response rates and prolonging the already achieved positive responses, Girard concludes.