Preface – ESMO 2021
Alex A. Adjei, MD, PhD, Professor of Oncology and Pharmacology Mayo Clinic, Rochester, USA Recipient of the ESMO Lifetime Achievement Award 2021
Dear Colleagues,
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. More than 22,700 participants from 143 countries registered for the ESMO Congress alone.
This issue of memo inOncology summarizes important findings relating to the management of patients with lung cancer that were presented at both conferences. Among druggable targets, those belonging to the EGFR/HER2 family play an important role in the pathogenesis of lung cancer. The critical role of this pathway is mirrored by the multitude of studies investigating drugs including poziotinib, mobocertinib, amivantamab, and trastuzumab deruxtecan. The antibody-drug conjugates telisotuzumab vedotin and datopotamab deruxtecan have been developed to target c-MET and TROP2, respectively. At the same time, new data are being generated on the ideal use of long-standing EGFR inhibitors such as erlotinib and afatinib.
Checkpoint inhibition is of course a pivotal pillar of treatment that has been established across all lines of therapy and is being implemented in other entities apart from non–small-cell lung cancer, such as small-cell lung cancer and mesothelioma. The combined administration of nivolumab and ipilimumab brought about progress with respect to unresectable malignant pleural mesothelioma. In stage III NSCLC, the PACIFIC trial has set a new standard after chemoradiotherapy of unresectable stage tumors. Consolidation with durvalumab was shown to be life-prolonging under real-world conditions, and combination regimens as well as other checkpoint inhibitors are being tested in the same setting. Patients with metastatic disease who have developed brain lesions derive benefit from checkpoint inhibitor regimens, while new CNS lesions can be prevented.
Anti-cancer vaccines have been evaluated unsuccessfully in NSCLC over the last decade. Therefore, the initial promising results for another type, the anti-cancer vaccine OSE-2101 that has demonstrated a favorable benefit-risk ratio after failure of immune checkpoint inhibition, are notable. Thus, thanks to the commitment of countless researchers, clinicians and patients, the available armamentarium for lung cancer therapy is being expanded to match the requirements of cancer treatment from early-stage to late-stage disease with the aim of providing maximum benefit in each given case.
© 2021 Springer-Verlag GmbH, Impressum
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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.
