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Risk tool for predicting toxicity from chemotherapy in older adults with early breast cancer

Older adults with early breast cancer may be at higher risk for toxicity from chemotherapy. The Cancer and Aging Research Group-Breast Cancer (CARG-BC) calculator was developed to predict toxicity from adjuvant chemotherapy specifically in older adults with early breast cancer, with better prediction than either Karnofsky Performance Status or the more general CARG score, in this subset [1]. Like the general CARG, it considers anemia, falls, limited mobility, and social factors, but also includes cancer stage, regimen, planned treatment duration, and liver function to refine its predictive ability. This tool can be used in risk-benefit discussions regarding adjuvant chemotherapy in older adults with early breast cancer.


Incidence and mortality from subsequent primary cancers among adult cancer survivors

Cancer survivors are at risk for developing a subsequent primary cancer (SPC). In a retrospective cohort study of approximately 1.5 million adult cancer survivors, the incidence and mortality rates from SPCs were increased for both men (11 and 45 percent) and women (10 and 33 percent) compared with the general population [2]. Survivors of laryngeal cancer and Hodgkin lymphoma were at highest risk. The most common SPCs were smoking or obesity-related (including lung, bladder, colorectal, and uterine cancer). These data strengthen the association between primary cancers and SPCs among adult cancer survivors and suggest opportunities to reduce risk with lifestyle interventions (eg, smoking cessation, alcohol counseling, diet, and physical activity) and cancer screening.


Early integration of supportive care for metastatic esophagogastric cancer

Patients with advanced esophagogastric cancer have a high incidence of malnutrition and psychologic distress, which may impair survival. The benefit of early supportive care was shown in a Chinese trial in which patients with previously untreated metastatic esophagogastric cancer who were randomly assigned to early interdisciplinary input with a focus on nutrition and psychological health integrated into standard oncologic care had significantly longer survival, better emotional and cognitive functioning, and less weight loss than did those receiving standard care alone [3]. All patients with newly diagnosed advanced gastric cancer should have a full assessment of symptom burden, nutritional and psychological status, and social supports as early as possible, ideally prior to starting systemic chemotherapy.


Neoadjuvant chemotherapy and pathologic response rates in muscle-invasive bladder cancer

For patients with muscle-invasive bladder cancer treated with neoadjuvant chemotherapy, options include dose dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) and gemcitabine plus cisplatin (GC), but the optimal treatment remains undefined. In a randomized phase III trial of approximately 440 patients with muscle-invasive disease, neoadjuvant ddMVAC and GC resulted in similar pathologic complete response rates (42 versus 36 percent) at cystectomy, but ddMVAC improved local control [4]. Based on these and other data, we suggest MVAC, and in some cases prefer a standard rather than dose dense schedule; but for older patients or less fit patients, alternative regimens such as GC are appropriate.


Adavosertib in platinum-resistant ovarian cancer

The Wee1 inhibitor adavosertib has shown efficacy in early-phase clinical trials in platinum-resistant ovarian cancer when combined with chemotherapy. In a double-blind randomized phase II trial in 124 women with recurrent platinum resistant high-grade serous ovarian cancer, those assigned to adavosertib plus gemcitabine had better progression-free survival than those assigned to gemcitabine alone (4.6 versus 3.0 months) [5]. Toxicities were largely hematologic. Larger studies are needed prior to use of adavosertib in ovarian cancer.


1. Magnuson A, Sedrak MS, Gross CP, et al. Development and Validation of a Risk Tool for Predicting Severe Toxicity in Older Adults Receiving Chemotherapy for Early-Stage Breast Cancer. J Clin Oncol 2021; :JCO2002063.


2. Sung H, Hyun N, Leach CR, et al. Association of First Primary Cancer With Risk of Subsequent Primary Cancer Among Survivors of Adult-Onset Cancers in the United States. JAMA 2020; 324:2521.


3. Lu Z, Fang Y, Liu C, et al. Early Interdisciplinary Supportive Care in Patients With Previously Untreated Metastatic Esophagogastric Cancer: A Phase III Randomized Controlled Trial. J Clin Oncol 2021; :JCO2001254.


4. Pfister C, Gravis G, Flechon A, et al. Randomized Phase III Trial of Dose-dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin, or Gemcitabine and Cisplatin as Perioperative Chemotherapy for Patients with Muscle-invasive Bladder Cancer. Analysis of the GETUG/AFU V05 VESPER Trial Secondary Endpoints: Chemotherapy Toxicity and Pathological Responses. Eur Urol 2021; 79:214.


5. Lheureux S, Cristea MC, Bruce JP, et al. Adavosertib plus gemcitabine for platinum-resistant or platinum-refractory recurrent ovarian cancer: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet 2021; 397:281.


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