ESMO 2021 Lung Cancer – Edward B. Garon

Edward B. Garon relates to anticancer vaccines, an area full of promises for lung cancer patients, their potential caveats compared to other novel treatment approaches, depicts the most interesting trial results from the phase I trial of intratumoral administration of CCL21-gene modified dendritic cells combined with intravenous pembrolizumab for advanced NSCLC and explains how antibody drug conjugates like datopotamab deruxtecan, a novel TROP2-directed ADC, fit in the therapeutic landscape in the future.

Here is the full ESMO 2021 Lung Cancer report.

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ATALANTE-1: anti-cancer vaccination after IO failure

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.

Gradual progress in the management of mesothelioma and thymoma

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.

Malignant pleural mesothelioma: immunotherapy-based approaches in all treatment lines

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.

Small-cell lung cancer: on the road to improved efficacy and tolerability

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.

Immunotherapy: boosting efficacy and overcoming resistance

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.

Innovative and established agents across a range of targets

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.