ESMO 2021: Cancer Research and Drug Development Highlights

Picture of the start of the ESMO21 virtual cancer conference - stage with speakers and podium
Image credit: ESMO

Over the last week, the world of cancer research, diagnostics and therapeutics has been congregating on the European Society of Medical Oncology (ESMO) website to view a wide variety of cutting-edge research presentations at the organization’s annual conference.

The biggest congress in Europe with a focus on cancer research, the event this year was held virtually for the second year in row due to concerns about COVID-19.

Some interesting highlights from the conference included a win for AstraZeneca and Daiichi Sankyo in the breast cancer space. The results from the Phase III DESTINY-Breast03 trial showed the antibody-drug conjugate (ADC) Enhertu (fam-trastuzumab deruxtecan-nxki), developed jointly by the two companies, reduced the risk of disease progression or death by 72% in HER2 positive breast cancer compared with Roche’s Kadcyla (trastuzumab emtansine).

A threefold improvement in progression free survival of 25.1 months with Enhertu versus 7.2 months with Kadcyla is impressive. Toxicity can be a problem with ADC drugs but although side effects were seen with Enhertu, they were all grades 1-3 and not the most serious grade 4-5 events.

Mirati Therapeutics is tackling non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) with a G12C mutation in the KRAS gene with its KRAS inhibitor adagrasib. It presented positive Phase I/II results for both indications, but with higher efficacy in the NSCLC group.

In the Phase II KRYSTAL-1 lung cancer study, which assessed treatment with adagrasib following systemic therapy, there was an objective response rate of 43% and a disease control rate of 80%. In the Phase I/II KRYSTAL-1 CRC study, patients had also already been treated with systemic therapy and then adagrasib. The adagrasib alone arm had a response rate of 22% but this did improve to 43% when combined with the CRC drug cetuximab.

Bristol Myers Squibb confirmed earlier practice changing results from the Phase III CheckMate 649 study, which trialed the checkpoint inhibitor nivolumab, either combined with chemotherapy or an additional checkpoint inhibitor ipilimumab, for first-line treatment of advanced gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma.

Nivolumab plus chemotherapy led to significantly improved overall survival at 12 months, as published in The Lancet earlier this year, and was approved for this indication by the US FDA earlier this summer. The results presented at ESMO were the 24-month follow-up data.

“It already changed practice for patients with metastatic gastric, esophageal and gastroesophageal -junction adenocarcinoma,” explained presenting author Yelena Janjigian (Memorial Sloan Kettering Cancer Center, New York).

However, the same was not true for the nivolumab plus ipilimumab arm, which failed to improve overall survival and actually reduced progression-free survival (2.8 months) compared with chemotherapy alone (6.3 months).

The Phase III KEYNOTE-826 trial in cervical cancer, which was simultaneously published in the NEJM, showed promising results for women who received immunotherapy with the checkpoint inhibitor pembrolizumab in addition to standard first-line treatment.

Adding pembrolizumab (Keytruda) to standard chemotherapy (with or without bevacizumab) extends survival by eight months compared with standard treatment.

Rare diseases were also represented, with a presentation of the first randomized study in malignant pheochromocytoma and paraganglioma (MPP), very rare neuroendocrine tumors. FIRSTMAPPP trial investigator and presenter Eric Baudin, Chair, Neuro-Endocrine Tumours, Gustave Roussy-Cancer Campus, Villejuif, France, and colleagues found that the small-molecule multi-targeted receptor tyrosine kinase inhibitor sunitinib prolonged progression-free survival by more than five months compared with placebo.

“This trial provides the highest level of evidence ever reached in this very rare cancer,” said Baudin in a press statement. “The results are practice-changing. Sunitinib is a new option for these patients and becomes the therapy with the most robust indication of antitumor activity in progressive malignant pheochromocytoma and paraganglioma. Based on these findings, new recommendations may consider sunitinib as the first line therapy in patients with this condition.”

These are just some of the interesting studies presented at ESMO21. More information about other research presented at the conference can be found on the ESMO conference website.

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