Ronan Kelly, MD, MBA – Director of the Charles A. Sammons Cancer Center at Baylor University Medical Center – Dallas, Texas, USA
Notable advances that have been achieved in the treatment of solid tumors were discussed at the virtual ESMO Congress 2020, among them remarkable results obtained in the field of gastroesophageal tumors. For patients with metastatic gastric and esophageal cancer, the long-term outcomes have remained poor, and several clinical trials over the last few years assessing PD-(L)1 inhibition have shown modest to negative results. However, the role of immune checkpoint inhibition in the treatment of these difficult-to-treat tumors came of age in September 2020 with an entire Presidential Symposium at virtual ESMO 2020 dedicated to likely practice-changing phase III trials both in the metastatic and, for the first time, in the adjuvant setting for operable disease.
Compared to chemotherapy alone, combinations of the PD-1 inhibitor nivolumab with chemotherapy gave rise to improved outcomes in the CheckMate 649 and ATTRACTION-4 studies that were conducted in the first-line setting. Overall survival was prolonged for the first time in a phase III trial beyond the 1-year boundary in patients with advanced gastric cancer who traditionally had a life expectancy of less than one year when treated with conventional chemotherapy. Similarly, the KEYNOTE-590 trial evaluating pembrolizumab plus chemotherapy in esophageal cancer revealed meaningful benefits with respect to several endpoints. These regimens will most likely provide new first-line standard of care in the future. Also, the adjuvant use of nivolumab post trimodality therapy for stage II/III esophageal/gastroesophageal junction cancers was successfully explored in the CheckMate 577 study, which revealed a doubling in disease-free survival compared to placebo. This trial is noteworthy not only by the fact that it is the first study ever to show a benefit of a novel treatment in early-stage esophagogastric cancers; also, after melanoma, it is the first trial to demonstrate the benefits of a PD-1 inhibitor in the adjuvant setting for any solid tumor and signals the start of a new era of immunotherapeutic use in early-stage malignancies.
Novel combination approaches are being investigated in a wide range of solid tumors including gastrointestinal cancers, gynecological cancers, breast cancer, lung cancer, renal cell carcinoma and urothelial carcinoma, among others. Studies reported at ESMO 2020 assessed combinations of immune checkpoint inhibitors with multikinase inhibitors. Innovation and refinement are also taking place in the context of PARP inhibition, which constitutes a mainstay of treatment of patients with ovarian cancer. In this indication, the combined administration of PARP inhibition, immunotherapy and anti-angiogenesis has shown promise as a chemotherapy-free option in the MEDIOLA trial. Pivotal phase II results have been generated for the investigational PARP inhibitor pamiparib that is also being assessed combined with temozolomide in various locally advanced or metastatic cancers.
Progress is undoubtedly being made across the full spectrum of malignancies with an improved understanding of the dynamic changes in the immune microenvironment and the evolution of the immune system as it seeks to keep up with an ever-changing tumor. This needs to be regarded as an integral area of research if we are to continue the impressive advances over the next decade.