Research focus – Antibody Drug Conjugates, Nuclear Medicine… Four other Breakthroughs to Watch
Last quarter also brought several other noteworthy developments. Researchers reported that delivering part of chemotherapy more precisely after surgery can help treat liver metastases, that antibody drug conjugates (ADCs) provide an additional treatment option in certain metastatic breast cancers, that nuclear medicine is showing encouraging results in metastatic pancreatic neuroendocrine tumours, and that new biomarkers could help identify which lung cancer patients are most likely to benefit from ADCs.
Reducing the Risk of Recurrence After Surgery for Liver Metastases
In some patients with colorectal cancer, metastases can develop in the liver. Even when these lesions are removed surgically, the risk of the disease returning in the liver remains substantial.
To better prevent recurrence, French research teams evaluated a more targeted strategy: following surgery, part of the chemotherapy is delivered directly into the artery supplying the liver, alongside standard intravenous chemotherapy.
The PACHA 01 trial, conducted in 99 patients who had undergone surgery for at least four liver metastases, showed that this approach reduced the risk of recurrence in the liver. Median hepatic recurrence-free survival increased from 12 months with standard intravenous administration to 25 months with targeted delivery through the hepatic artery.
These findings, obtained in a phase II trial, will need to be confirmed in a larger phase III study. They nevertheless represent a promising avenue for patients at high risk of recurrence following surgery.
Postoperative Hepatic Arterial Infusion With Oxaliplatin After Surgery of Four or More Colorectal Liver Metastases: A Randomized Phase II Trial
Gelli, M., et al., Journal of Clinical Oncology, Volume 44, Number 15, 22 April 2026.
A New Treatment Option in Certain Breast Cancers
In patients with hormone receptor positive (HR-positive), HER2-negative metastatic breast cancer, the disease may continue to progress despite treatment. The phase III TROPION-Breast01 trial evaluated datopotamab deruxtecan, a treatment belonging to the ADC class. ADCs combine an antibody that recognises a target present on tumour cells with a chemotherapy payload, allowing treatment to be delivered more selectively.
Although the final analysis did not demonstrate a significant improvement in overall survival, the study, which included 732 patients, showed that datopotamab deruxtecan delayed disease progression more effectively than conventional chemotherapy. Response rates and disease control at 12 weeks were also higher with datopotamab deruxtecan.
Another important finding was that severe treatment-related adverse events were less frequent with this ADC than with standard chemotherapy. These results support datopotamab deruxtecan as a new therapeutic option for certain patients with metastatic breast cancer.
Datopotamab deruxtecan versus chemotherapy in previously treated inoperable/metastatic hormone receptor-positive, HER2-negative breast cancer: final overall survival analysis of the phase III TROPION-Breast01 study
Pistilli, B., et al., Annals of Oncology, Volume 37, Issue 5, May 2026.
Nuclear Medicine in the Management of Metastatic Pancreatic Neuroendocrine Tumours
Pancreatic neuroendocrine tumours (NETs) are rare cancers arising from neuroendocrine cells capable of producing hormones. In the metastatic setting, treatment options include hormone therapy, two targeted therapies and chemotherapy. Peptide receptor radionuclide therapy (PRRT), a form of nuclear medicine, is also approved for this indication. However, it is not currently reimbursed in France because dedicated clinical trial data have been lacking.
The French academic OCLURANDOM study, a randomised phase II clinical trial sponsored by Gustave Roussy, evaluated the nuclear medicine agent lutetium Lu-177 dotatate in patients with metastatic pancreatic neuroendocrine tumours expressing somatostatin receptors, a characteristic that enables more precise targeting of tumour cells.
This approach was compared with sunitinib, one of the two targeted therapies already approved in this setting. One year after treatment initiation, disease progression had not occurred in 80.5% of patients treated with lutetium Lu-177 dotatate, compared with 41.9% of those receiving sunitinib. After six years of follow-up, progression-free survival also remained longer in the lutetium-treated group.
From a tolerability perspective, patients receiving nuclear medicine reported a better quality of life during treatment. Nevertheless, the persistence of some adverse effects after treatment discontinuation raises questions about tolerance to subsequent lines of therapy. Despite this, the study highlights substantial antitumour activity in pancreatic neuroendocrine tumours. As is often the case in rare diseases, no dedicated phase III trial is currently planned to confirm these findings. However, a new reimbursement application has been submitted in light of these positive results.
[177Lu]Lu-dota-tate versus sunitinib in patients with metastatic progressive neuroendocrine tumours of the pancreas (OCLURANDOM): a randomised, controlled, phase 2 trial
Baudin, E., et al., The Lancet Oncology, Volume 27, Issue 6, June 2026.
Towards a Better Understanding of ADCs in Lung Cancer
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. In advanced disease, some patients may benefit from targeted therapies or immunotherapy, but treatment options become limited once the disease progresses despite these approaches.
The ICARUS-LUNG01 study, conducted in 100 previously treated patients, evaluated datopotamab deruxtecan, an ADC targeting the TROP2 protein expressed on tumour cells. This treatment combines an antibody with a chemotherapy payload delivered in a more targeted manner.
The results showed genuine, although modest, antitumour activity. An objective response was observed in 26% of patients, while median progression-free survival reached 3.6 months. The benefit appeared greater among patients with non-squamous NSCLC.
The most important contribution of this study, however, may lie in the biological insights it provides. Analyses suggest that the ability of tumour cells to internalise TROP2, and therefore the ADC itself, may influence treatment response. Conversely, activation of DNA repair mechanisms could contribute to resistance to datopotamab deruxtecan.
These findings will need to be confirmed in larger studies, but they point towards an important future objective: identifying more accurately which patients are most likely to benefit from these new targeted therapies.
Efficacy, safety, and biomarker analysis of datopotamab deruxtecan in advanced non-small cell lung cancer: ICARUS-LUNG01 phase 2 study
Planchard, D., et al., Cancer Cell, Volume 44, Issue 6, 8, June 2026.