Highlights from cancer research and drug development

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Image credit: ESMO

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

Europe’s largest cancer research-focused congress, the event was held this year for virtually the second year in a row amid concerns about COVID-19.

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

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

Mirati Therapeutics tackles 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 superior efficacy in the NSCLC group.

In phase II Lung cancer KRYSTAL-1 study, which evaluated treatment with adagrasib after systemic therapy, there was an objective response rate of 43% and a disease control rate of 80%. In Phase I / II KRYSTAL-1 CRC study, the patients had also previously been treated with systemic therapy followed by adagrasib. The adagrasib arm alone had a response rate of 22%, but this improved to 43% when combined with the CRC drug cetuximab.

Bristol Myers Squibb confirmed that past practices affected the results of the Phase III CheckMate 649 who tested the checkpoint inhibitor nivolumab, either in combination with chemotherapy or with an additional checkpoint inhibitor, ipilimumab, for the first-line treatment of advanced gastric cancer, gastric junction cancer esophageal or esophageal adenocarcinoma.

Nivolumab plus chemotherapy led to a significant improvement in 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 to ESMO were 24-month follow-up data.

“This has already changed the practice for patients with metastatic adenocarcinoma of the stomach, esophagus and gastroesophageal junction,” explained presenter 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 in fact reduced progression-free survival (2.8 months) compared to chemotherapy alone ( 6.3 months).

The phase III trial KEYNOTE-826 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 therapy.

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

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

“This trial provides the highest level of evidence ever in this very rare cancer,” Baudin said in a press release. “The results change the practice. Sunitinib is a new option for these patients and is becoming the therapy with the strongest indication of antitumor activity in progressive malignant pheochromocytoma and paraganglioma. Based on these results, new recommendations may consider sunitinib as the first-line treatment in patients with this disease.

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


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