Getting innovation from the laboratories into clinical practice
Andrés Cervantes, MD, PhD, Department of Medical Oncology, Hospital Clinic Universitario, Biomedical Research institute INCLIVA, University of Valencia, Spain
Which data presented at ESMO 2020 in the field of gastric cancer, gastroesophageal junction adenocarcinoma and esophageal cancer do you deem practice-changing?
The ESMO congress has provided amazing new data on gastroesophageal cancer, and great contributions by different authors all over the world have been presented. Patients with advanced gastric cancer used to have a median overall survival of less than 1 year when treated with conventional chemotherapy. For the first time, this was prolonged to more than 1 year due to the addition of checkpoint inhibition. Two randomized studies were reported at the Presidential Symposium III that showed outcome improvement for patients with gastric and gastroesophageal junction cancer when nivolumab was added to conventional chemotherapy [1, 2]. These are amazing findings, specifically for esophageal cancer that is also a very difficult disease and for which no new treatments have been developed over the last years. In patients with advanced or metastatic esophageal cancer, the addition of pembrolizumab, another checkpoint inhibitor, improved the response rate, progression-free survival and overall survival . I also want to underline the findings obtained for nivolumab as postoperative treatment in patients with esophageal cancer who had received neoadjuvant chemoradiotherapy before surgery . The preliminary data from this adjuvant study showed a significant prolongation of median disease-free survival of almost 1 year.
What has recently been achieved with regard to hepatocellular carcinoma?
The therapeutic landscape in hepatocellular carcinoma is evolving rapidly. At the ESMO Asia 2019, results for the combination of atezolizumab and bevacizumab, which is now the standard of care for first-line treatment of patients with advanced disease, was presented for the first time . This year at ESMO, at the oral session of gastrointestinal non-colorectal cancers, an innovative approach assessed at the University of Guangzhou in South China was reported . For patients with stage B hepatocellular carcinoma, the standard of care is transarterial chemoembolization, which was compared with hepatic intraarterial infusional chemotherapy with FOLFOX in more than 300 patients. The results of this randomized study showed that intraarterial chemotherapy is superior to transarterial chemoembolization, which means a new standard of care. I am sure that this approach will be incorporated into clinical practice.
Which emerging data with novel immunotherapeutic compounds are likely to impact future clinical research?
I recommend watching the session on investigational immunotherapy at the ESMO 2020 as it provided a lot of information on new drugs and new ways of delivering immunotherapy. Most of these novel compounds are combined with checkpoint inhibitors. The new approaches include a fusion protein of interleukin-2 and interleukin-2 receptor alpha  as well as adoptive cell therapy with tumor-infiltrating lymphocytes in combination with checkpoint inhibitors in patients with various cancers . Compounds have been developed with different mechanisms of action addressing new receptors such as TIM-3.
I really think that it is worthwhile to have a look at all these new possibilities that have been tested in phase I studies. In my opinion, they will be assessed in more advanced trials over the next few years. There is hope and many new data, and these data should be further developed to establish new approaches in the clinic. Getting innovation from the laboratories into clinical practice is the aim of our work.
What are your personal highlights from ESMO 2020?
For one, there are combinations of immunotherapy with targeted agents. An example of this is the study on the combined treatment with nivolumab and cabozantinib in patients with renal cell carcinoma that was presented at the Presidential Symposium I . Compared to sunitinib, the combination demonstrated superior activity. Secondly, I would want to highlight the importance of early treatment in the setting of immunotherapy. These agents should not be used for refractory disease; they are gaining acceptance in first line and even in the adjuvant setting. The trial on adjuvant nivolumab in esophageal cancer is an example of this. Also, I want to point out new targeted agents such as the specific AKT inhibitor ipatasertib that has been shown to add to survival in patients with castration-resistant prostate cancer treated in a phase III trial .
- Boku N et al., Nivolumab plus chemotherapy versus chemotherapy alone in patients with previously untreated advanced or recurrent gastric/gastroesophageal junction cancer: ATTRACTION-4 (ONO-4538-37) study. ESMO 2020, LBA7_PR
- Möhler M et al., Nivolumab plus chemotherapy versus chemotherapy as first-line treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma: first results of the CheckMate 649 study. ESMO 2020, LBA6_PR
- Kato K et al., Pembrolizumab plus chemotherapy versus chemotherapy as first-line therapy in patients with advanced esophageal cancer: the phase 3 KEYNOTE-590 Study. ESMO 2020, LBA8_PR
- Kelly RJ et al., Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer following neoadjuvant chemoradiation therapy: first results of the CheckMate 577 study. ESMO 2020, LBA9
- Chen AL et al., IMbrave150: Efficacy and safety results from a phase III study evaluating atezolizumab + bevacizumab vs sorafenib as first treatment for patients with unresectable hepatocellular carcinoma. ESMO Asia 2019, LBA3
- Shi M et al., Hepatic arterial infusion chemotherapy with oxaliplatin, fluorouracil, and leucovorin (FOLFOX) versus transarterial chemoembolization for unresectable hepatocellular carcinoma: A randomised phase III trial. ESMO 2020, 9810
- Vaishampayan UN et al., ALKS 4230 monotherapy and in combination with pembrolizumab in patients with refractory solid tumours (ARTISTRY-1). ESMO 2020, 1027MO
- Kverneland AH et al., Clinical potential of adoptive cell therapy with tumour infiltrating lymphocytes therapy in combination with checkpoint inhibitors in non-melanoma patients. ESMO 2020, 1022MO
- Choueiri TK et al., Nivolumab + cabozantinib vs sunitinib in first-line treatment for advanced renal cell carcinoma: first results from the randomized phase 3 CheckMate 9ER trial. ESMO 2020, 6960_PR
- de Bono JS et al., IPATential150: Phase III study of ipatasertib plus abiraterone vs placebo plus abiraterone in metastatic castration-resistant prostate cancer. ESMO 2020, LBA4
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