Patients with EGFR-wildtype, advanced NSCLC in the second or third treatment line represent a large population with limited treatment options. A novel approach is the first-in-class selective immunomodulating microtubule-binding agent (SIMBA) plinabulin that releases the immune defense protein GEF-H1, thus inducing dendritic cell maturation, which is a key step in the initiation of durable anti-cancer response.
OSE-2101 is an anti-cancer vaccine with modified neoepitopes restricted to HLA-A2+ targeting the tumor-associated antigens CEA, p53, HER2, MAGE-2 and MAGE-3 that are frequently expressed in lung cancer. HLA-A2 is assessed in the serum and is positive in approximately half of patients.
This is an important field where little progress has been made in the past. At ESMO 2021, updated results of the randomized CheckMate-743 trial of nivolumab plus ipilimumab versus chemotherapy were presented by Prof. Peters. The overall survival benefit was pronounced in patients with PD-L1–positive or non-epithelioid mesotheliomas, although there was an OS benefit in the total population.
The randomized phase III CheckMate 743 trial evaluated nivolumab 3 mg/kg Q2W plus ipilimumab 1 mg/kg Q6W for up to 2 years compared with cisplatin or carboplatin plus pemetrexed Q3W for 6 cycles as first-line treatment of patients with unresectable malignant pleural mesothelioma (MPM). More than 300 patients were randomized into each study arm.
Lurbinectedin, a selective inhibitor of oncogenic transcription, has been approved at a dose of 3.2 mg/m2 Q3W for the treatment of patients with small-cell lung cancer (SCLC) showing disease progression on or after platinum-based chemotherapy in the US. The randomized, phase III ATLANTIS trial tested the combination of lurbinectedin 2 mg/m2 and doxorubicin 40 mg/m2 Q3W for a maximum of 10 cycles followed by lurbinectedin 3.2 mg/m2 Q3W in 307 patients with relapsed SCLC after one prior chemotherapy line.
The global, randomized, open-label, phase III POSEIDON trial evaluated the PD-L1 inhibitor durvalumab with or without the anti-CTLA-4 antibody tremelimumab in addition to chemotherapy as a first-line strategy in the setting of metastatic NSCLC. At 153 sites in 19 countries, 1,013 patients with squamous or non-squamous, stage IV NSCLC were randomized into three arms.
HER2 mutations constitute the predominant driver aberration in approximately 3 % of non-squamous NSCLC cases. While approved HER2-targeted therapies for patients with NSCLC are still lacking, the anti-HER2 antibody-drug conjugate trastuzumab deruxtecan (T-DXd) has been licensed in various countries for use in other HER2-positive entities.
The management of patients with stage I-III non–small-cell lung cancer (NSCLC) is still characterized by a high unmet medical need as up to 60 % experience disease relapse despite treatment with curative intent [1]. IMpower010 was the first phase III study of cancer immunotherapy to demonstrate a disease-free survival (DFS) benefit in the adjuvant situation after complete resection and platinum-based chemotherapy.
With the World Conference on Lung Cancer that took place on 8th–14th September 2021 and the ESMO Congress on 16th–21st September, two prestigious cancer congresses have offered a wealth of new preclinical and clinical information in the field of lung cancer. Results from pivotal studies were updated, and fascinating novel treatment approaches were presented to large audiences around the world.
