In this edition of the Esmo Congress underway in Madrid, the abstracts and studies presented on lung cancer are among the most numerous and the enthusiasm among the 31 thousand oncologists participating in the various symposia is high. Among the data considered most promising are those concerning early-stage patients for whom having new therapy regimens available can mean an extension of survival. Giving new hope are the results of the Phase 3 Keynote-671 study which evaluated pembrolizumab, MSD’s anti-PD-1 therapy, as a perioperative therapeutic regimen, which involves treatment before surgery (neoadjuvant) and after surgery (adjuvant ), of patients with resectable stage II, IIIA or IIIB non-small cell lung cancer (NSCLC). Data which shows that in early-stage lung cancer, immunotherapy with pembrolizumab, before and after surgery, reduces the risk of death by 28% and improves overall survival, with 71% of patients alive at 3 years. The new data is presented for the first time in the proffered paper session of the 2023 Congress of the European Society for Medical Oncology.
Esmo 2023 Breast cancer: pollution increases the risk by 28% by Irma D’Aria 19 October 2023
The increase in survival
At the planned second interim analysis with a median follow-up of 36.6 months, neoadjuvant pembrolizumab plus chemotherapy followed by single-agent pembrolizumab after surgical resection significantly improved overall survival, reducing the risk of death by 28% in patients with Resectable stage II, IIIA, or IIIB NSCLC compared with neoadjuvant placebo plus chemotherapy followed by adjuvant placebo, regardless of PD-L1 expression. In patients treated with the pembrolizumab-based regimen, the median overall survival was not reached compared to 52.4 months in patients treated with the chemotherapy-placebo regimen. Until now, pembrolizumab has established itself as a fundamental treatment for some advanced lung cancers, but now these overall survival results highlight the role of pembrolizumab also in patients with early stages of the disease, who need new therapeutic options that can help them to live longer.
Esmo 2023 Tumors: 50% of patients have social discomfort, but in 70% of cases they are not treated by Irma D’Aria 20 October 2023
The disease in its early stages
Overall survival rates at 36 months were 71.3% for patients treated with the pembrolizumab regimen compared to 64% for those treated with the chemotherapy-placebo regimen. “In 2022, in Italy, approximately 44 thousand new cases of lung cancer have been estimated – he explains Silvia Novello, full professor of Medical Oncology at the University of Turin and Head of Pulmonary Oncology at the San Luigi Gonzaga Hospital in Orbassano – and there is still a strong unmet clinical need for these patients because, even when the disease is diagnosed in the initial phase, Recurrence rates after surgery remain high and the Keynote-671 study scheme has demonstrated a significant impact on this too. The pembrolizumab-based regimen, before and after surgery, significantly reduces the risk of death by 28% compared to preoperative chemotherapy, regardless of PD-L1 expression.”
Esmo 2023 Esmo 2023, the Israeli-Palestinian war keeps 150 researchers out of Congress by Irma D’Aria 20 October 2023
How event-free survival changes
The Keynote-671 study met the second primary endpoint of event-free survival at the first interim analysis. At this second analysis, the event-free survival (EFS) benefit observed in the previous analysis was maintained and the pembrolizumab arm improved median EFS by approximately 2.5 years compared to the placebo-chemotherapy arm versus 18.3 months respectively . The 36-month EFS rates were 54.3% in patients treated with the pembrolizumab regimen compared to 35.4% in those treated with the chemotherapy-placebo regimen. “The results of the KEYNOTE-671 study represent an important step forward and will allow us to improve the therapeutic results of patients with resectable non-small cell lung cancer – continues Novello. Pembrolizumab plus chemotherapy before surgery and followed as a single agent after surgery has the potential to become a fundamental strategy that can modify the history of this early-stage neoplasm, significantly increasing its chances of cure”. MSD previously announced that, based on OS and EFS results from the KEYNOTE-671 study, the US Food and Drug Administration (FDA) approved pembrolizumab for the treatment of patients with resectable NSCLC in combination with platinum-based chemotherapy as treatment neoadjuvant and then continued as a single agent in the adjuvant treatment after surgery. There is a large clinical development program for pembrolizumab in lung cancer and several pivotal studies are underway, with research directed at early stages of the disease and new combinations. Data covering more than 15 different tumor types from MSD’s extensive oncology portfolio and investigative pipeline will be presented at ESMO Congress 2023.
Lung cancer
Lung cancer is the leading cause of death worldwide. In 2020 alone, there were more than 2.2 million new cases and approximately 1.8 million deaths from lung cancer globally. Non-small cell lung cancer is the most common type, accounting for approximately 81% of all cases. In the United States, the five-year overall survival of lung cancer patients is 25%, which constitutes a 21% improvement over the past five years. The improvement in survival rates is due in part to the advancement of diagnostic and surgical procedures, but also to the introduction of new therapies. However, rates of screening, early diagnosis, and treatment advances remain an important unmet need, as 44% of lung cancer cases are diagnosed at an advanced stage. Only 5.8% of eligible people in the United States have undergone lung cancer screening.
The importance of early diagnosis
Having effective therapies available at increasingly earlier stages makes early diagnosis even more important. “Just 15 days ago – explains Novello – we exceeded the objectives set by the Risp national screening program which was 7 thousand patients: we screened 9 thousand of them. Interrupting this ‘machine’ right now would be a shame because it is working well in at least 18 centers Italians”.