New drug treatments for advanced breast and rectal cancers show promise.


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A recent study in the New England Journal of Medicine has found that trastuzumab deruxtecan, a drug used to treat breast cancers with high levels of human epidermal growth factor receptor 2 (HER2), is also effective in treating breast cancers low in HER2, which until now have had few treatment options. Of 557 patients with unresectable, metastatic HER2-low breast cancers, 373 received trastuzumab deruxtecan and 184 underwent standard chemotherapy. In the trastuzumab deruxtecan group, the median progression-free survival was 9.9 months, and the median overall survival was 23.4 months (compared with 5.1 and 16.8 months, respectively, in the standard chemotherapy group).


An antibody-drug conjugate, trastuzumab deruxtecan not only targets HER2 cancer cells, but also passes through the membranes of the cancer cells to kill neighboring tumor cells. The most common adverse effects among those who received the drug included nausea, fatigue, and alopecia. Pneumonitis, while less frequent, was an important risk of taking the drug, affecting about 12% of patients.


The study, the researchers say, shows that trastuzumab deruxtecan can improve treatment outcomes for patients with HER2-low breast cancers, who-because of an erroneous binary categorization of HER2 status (positive versus negative)-were until now considered to be HER2 negative.


Another study, also in the New England Journal of Medicine, offered astounding results for locally advanced rectal cancers with mismatch repair deficiency-which make up about 5% to 10% of rectal adenocarcinomas and are typically unresponsive to standard chemotherapy. Of 12 patients who completed treatment with the drug dostarlimab, administered intravenously, and who underwent at least six months of follow-up, 100% had complete remission, with no evidence of tumor on magnetic resonance imaging, positron-emission tomography, endoscopic evaluation, digital rectal examination, or biopsy.


In addition, during follow-up (ranging from six to 25 months), none of the patients needed subsequent chemoradiotherapy or surgery, which, as the researchers point out, can have devastating effects on fertility, sexual health, and bowel and bladder function, and may lead to a colostomy. Therapeutic responses were rapid, with 81% of patients experiencing a resolution of tumors within nine weeks of treatment initiation. The most common adverse effects included rash or dermatitis, pruritus, fatigue, and nausea; one patient exhibited thyroid function abnormalities.


The researchers recommend that the study be reproduced on a larger scale, with the participation of patients from various racial and ethnic backgrounds.-Dalia Sofer


Modi S, et al N Engl J Med 2022;387(1):9-20; Cercek A, et al. N Engl J Med 2022;386(25):2363-76.