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Fam-trastuzumab deruxtecan in HER2-low breast cancer (June 2022)
Studies are evaluating anti-HER2 directed therapy in "HER2-low" tumors (ie, those with 1+ on immunohistochemical [IHC] analysis; or an IHC score of 2+ and negative results on in situ hybridization). In a randomized trial among 557 patients with HER2-low metastatic breast cancer who had received one or two previous lines of chemotherapy, the anti-HER2 antibody-drug conjugate fam-trastuzumab deruxtecan resulted in a median progression-free survival of 9.9 versus 5.1 months with physician's choice treatment (hazard ratio [HR] 0.50); median overall survival was 23 versus 17 months, respectively (HR 0.64) [1]. Benefits were comparable in the hormone receptor-positive and hormone receptor-negative subgroups. Based on these results, we consider fam-trastuzumab deruxtecan to be an appropriate later line option for HER2-low advanced breast cancers, although regulatory approval in this setting is pending.
New gastrointestinal hamartomatous polyposis syndromes guideline (June 2022)
The United States Multi-Society Task Force (USMSTF) for Colorectal Cancer has published a new clinical guideline on the diagnosis and management of gastrointestinal hamartomatous polyposis syndromes [2]. In patients with Peutz-Jeghers syndrome, the guideline suggests upper gastrointestinal endoscopy and colonoscopy starting between 8 and 10 years of age and video capsule beginning at age 8 years. It also suggests screening for pancreatic cancer with alternating magnetic resonance imaging/magnetic resonance cholangiopancreatography or endoscopic ultrasound of the pancreas every one to two years, beginning at age 35 years. Our approach is consistent with the guideline.
Cardiovascular effects of radiation for lung cancer (June 2022)
The effect of radiation for lung cancer on cardiovascular outcomes is being explored. In a registry study including over 3200 patients, rates of adverse cardiovascular outcomes with three-dimensional conformal radiation therapy with intensity modulated radiation therapy (3DCRT-IMRT) for left-sided tumors were higher than for right-sided tumors, presumably because of higher radiation doses to cardiac tissues [3]. However, among those receiving stereotactic body radiation therapy (SBRT), cardiovascular outcomes were similar for left- versus right-sided tumors. This study suggests SBRT may be a safer option than 3DCRT-IMRT for those with left-sided lung cancer.
Cancer mortality in the United States during the COVID-19 pandemic (June 2022)
Many patients experienced delays in cancer screening and treatment during the COVID-19 pandemic, but data were limited on cancer-specific mortality during this period. In an observational study from the American Cancer Society, the number of cancer-related deaths in the United States increased by 3 percent between 2019 (prior to the pandemic) and 2020 (during the pandemic), with higher cancer mortality rates noted during the times when health care capacity was most challenged during the pandemic [4]. Based on these data, we continue to strongly encourage cancer screening, based on the extent of community transmission of COVID-19 and availability of resources.
Treatment of precancerous anal lesions in people living with HIV (June 2022)
In persons living with HIV, anal high-grade squamous intraepithelial lesions (HSIL) are a risk factor for anal cancer, but whether treatment of HSIL reduces risk has not been tested prospectively. In the ANCHOR trial in which nearly 4500 individuals age >=35 years with HIV and HSIL were randomly assigned to treatment (ablation, excision, or topical therapy) or active monitoring, treatment reduced the risk of progression to invasive cancer by 57 percent (95% CI 6-80) at a median follow up of 26 months [5]. The rate of treatment-related serious adverse events was low overall (7 of 2227) and included skin ulceration, anal abscess, and treatment-related pain. Given these results, for most patients with HSIL, we suggest treatment rather than observation.
1. Modi S, Jacot W, Yamashita T, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022;387(1):9. Epub 2022 Jun 5.
2. Boland CR, Idos GE, Durno C, et al. Diagnosis and Management of Cancer Risk in the Gastrointestinal Hamartomatous Polyposis Syndromes: Recommendations From the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2022;162(7):2063. Epub 2022 Apr 26.
3. Liu BY, Rehmani S, Kale MS, et al. Risk of Cardiovascular Toxicity According to Tumor Laterality Among Older Patients With Early Stage Non-small Cell Lung Cancer Treated With Radiation Therapy. Chest. 2022;161(6):1666. Epub 2022 Jan 19.
4. Zhao J, Han X, Miller K, et al. Changes in cancer-related mortality during the COVID-19 pandemic in the United States. J Clin Oncol. 2022;40;16S
5. Palefsky JM, Lee JY, Jay N, et al. Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer. N Engl J Med. 2022;386(24):2273.
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