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Choice of adjuvant bisphosphonate in early breast cancer

For select women treated with adjuvant systemic therapy for early breast cancer, incorporation of bisphosphonates improves cancer outcomes, but the optimal agent is unclear. In SWOG 0307, 6000 women with stage I to III breast cancer were randomly assigned to adjuvant clodronate, ibandronate, or zoledronic acid [1]. Disease-free and overall survival were similar between the groups, but ibandronate resulted in the highest rate of grade 3/4 toxicities. When an adjuvant bisphosphonate is indicated for early breast cancer, we suggest zoledronic acid or clodronate.


AGA guidelines for managing patients at risk for hereditary pancreatic cancer

The American Gastroenterological Association (AGA) has published updated guidelines on identification and management of patients at risk for hereditary pancreatic cancer (PC) [2]. The AGA recommends screening for PC in patients with genetic syndromes associated with an increased risk of pancreatic cancer (Peutz-Jeghers syndrome; germline carriers of pathogenic variants in CDKN2A, BRCA1, BRCA2, PALB2, and ATM genes; genes associated with Lynch syndrome), patients with one or more first-degree relatives with PC, and those with hereditary pancreatitis associated with a PRSS1 mutation. Consistent with other guidelines, the AGA also suggests that in patients at risk for PC, identification of new onset-diabetes should prompt urgent imaging to screen for an underlying pancreatic neoplasm.


Maintenance avelumab in advanced urothelial bladder cancer

Patients with advanced bladder cancer often experience only short durations of disease control after platinum-based chemotherapy, leading to interest in maintenance therapies. In a phase 3 trial (JAVELIN Bladder 100) of 700 patients with locally advanced unresectable or metastatic urothelial carcinoma of the bladder without progression on gemcitabine plus platinum-based chemotherapy, at follow-up of 19 months, maintenance avelumab improved overall survival relative to best supportive care in both the entire study population (median 21 versus 14 months) and those with PD-L1 positive tumors (not reached versus 17 months) [3]. Maintenance avelumab was well tolerated. Based on these data, the US Food and Drug Administration approved the use of maintenance avelumab for patients with advanced or metastatic urothelial carcinoma of the bladder who have not progressed on initial treatment with platinum-based chemotherapy [4], and we also suggest its use in such patients.


Postoperative chemoradiation for locoregionally advanced squamous cell carcinoma of the head and neck

In patients with locoregionally advanced squamous cell carcinoma of the head and neck (HNSCC) treated with postoperative chemoradiation (CRT), the optimal dosing of cisplatin concurrent with radiation therapy (RT) is not established. In a randomized phase II/III trial (JCOG1008) of approximately 260 patients with Stage III-IVB high risk HNSCC receiving surgery and postoperative CRT, weekly dosing of cisplatin (40 mg/m2 for up to seven doses) concurrent with RT demonstrated non-inferior three-year overall survival (72 versus 59 percent) and a better toxicity profile versus bolus dosing of cisplatin (100 mg/m2 every three weeks) [5]. Based on these data, for patients with locoregionally advanced, resected HNSCC who require postoperative CRT, we recommend weekly dosing of cisplatin (40 mg/m2) concurrent with RT.


Apixaban and venous thromboembolism in patients with cancer

Direct oral anticoagulants (DOACs) are increasingly used in patients with acute venous thromboembolism (VTE) and active cancer, but studies comparing their safety and efficacy with low molecular weight heparin (LMWH) are limited. In a recent study, the DOAC apixaban resulted in similar rates of VTE when compared with the LMWH dalteparin (5.6 versus 7.9 percent) without any impact on major bleeding events (3.8 versus 4 percent) [6]. Apixaban is now considered a suitable alternative to LMWH in patients with VTE and active cancer.


1. Gralow JR, Barlow WE, Paterson AHG, et al. Phase III Randomized Trial of Bisphosphonates as Adjuvant Therapy in Breast Cancer: S0307. J Natl Cancer Inst 2020; 112:698.


2. Aslanian HR, Lee JH, Canto MI. AGA Clinical Practice Update on Pancreas Cancer Screening in High-Risk Individuals: Expert Review. Gastroenterology 2020.


3. Powles T, Park SH, Voog E, et al. Maintenance avelumab + best supportive care (BSC) versus BSC alone after platinum-based first-line (1L) chemotherapy in advanced urothelial carcinoma (UC): JAVELIN Bladder 100 phase III interim analysis. J Clin Oncol 2020; 38S.


4. Avelumab - United States Food and Drug Administration Label. (Accessed on July 02, 2020).


5. Kiyota N, Tahara M, Fujii H, et al. Phase II/III trial of post-operative chemoradiotherapy comparing 3-weekly cisplatin with weekly cisplatin in high-risk patients with squamous cell carcinoma of head and neck (JCOG1008). J Clin Oncol 2020; 38:15S.


6. Agnelli G, Becattini C, Meyer G, et al. Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer. N Engl J Med 2020.


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