Daily highlight in metastatic NSCLC

Reported by Prof Els Wauters – University Hospitals Leuven

In the phase 3 SAPPHIRE trial, researchers investigated the impact of sitravatinib in combination with nivolumab versus docetaxel in NSCLC patients who had initially responded to immune checkpoint inhibition (defined as a minimum 4-month treatment) but later developed resistance. Despite preclinical and early clinical evidence suggesting sitravatinib’s potential to sensitise tumours to immune checkpoint inhibition again, the trial did not demonstrate a significant improvement in overall survival, the primary endpoint.

The KRYSTAL-7 trial explored the challenging combination of adagrasip-mediated immune checkpoint inhibition and pembrolizumab targeted therapy. Hepatic toxicity, a significant concern with this combination, was carefully examined. Encouragingly, the study reported favourable data regarding side effects like nausea and diarrhoea as well as hepatic toxicity. Preliminary efficacy data, especially in patients with tumour PD-L1 expression of at least 50%, were promising.

In the ATTLAS study, researchers compared carboplatin-paclitaxel combined with adagrasib and bevacizumab against the current standard of care (platinum-pemetrexed) in EGFR-mutated patients with acquired resistance to EGFR-TKIs who received immune checkpoint inhibition. The study revealed significantly prolonged progression-free survival in patients with EGF mutations. However, further exploration of the regimen’s benefits and risks is necessary, along with the identification of biomarkers to determine its position in first- and second-line treatments for advanced EGFR-mutated NSCLC.

The ACHILLES phase 3 study assessed the efficacy of afatinib treatment compared to chemotherapy as a first-line option for patients with uncommon sensitising EGFR mutations, a group often excluded from EGFR TKI trials. Afatinib demonstrated significantly improved progression-free survival, the primary endpoint. Both treatment arms exhibited similar frequencies of treatment-related adverse events. Although afatinib proved effective, it did not demonstrate superiority over third-generation EGFR TKIs.

References:

Hossein Borghaei – SAPPHIRE: Phase 3 Study of Sitravatinib Plus Nivolumab Versus Docetaxel in Patients With Previously Treated Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC) – ESMO 2023 – LBA63

Marina C. Garassino – KRYSTAL-7: Efficacy and safety of adagrasib with pembrolizumab in patients with treatment-naïve, advanced non-small cell lung cancer (NSCLC) harboring a KRASG12C mutation – ESMO 2023 – LBA65

Myung-Ju Ahn – A Phase 3, Randomized study of atezolizumab plus bevacizumab and chemotherapy in patients with EGFR or ALK mutated in non-small cell lung cancer (ATTLAS, KCSG-LU19-04) – ESMO 2023 – LBA67

Satoru Miura -Afatinib versus chemotherapy for treatment-naïve non-small cell lung cancer with a sensitizing uncommon epidermal growth factor receptor mutation: a phase III study (ACHILLES/TORG1834) – ESMO 2023 – LBA66