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Bevacizumab plus chemotherapy for initially unresectable liver-limited metastatic RAS-mutant metastatic colorectal cancer

Bevacizumab has only modestly improved resectability rates when added to an oxaliplatin-containing chemotherapy backbone, and whether the benefits outweigh the risks in patients undergoing conversion therapy for potentially resectable colorectal cancer (CRC) liver metastases has been controversial. In the BECOME randomized trial of patients with RAS mutant initially unresectable but liver-limited, metastatic CRC, the addition of bevacizumab to oxaliplatin plus leucovorin and short term infusional fluorouracil (FOLFOX) was associated with higher rates of objective response and a nearly four-fold increase in the complete (R0) resection rate (22 versus 6 percent) [1]. We now consider that bevacizumab plus an oxaliplatin-containing regimen is an option for conversion therapy in those with RAS mutant CRC liver metastases. For most other patients, we prefer an oxaliplatin-containing combination regimen without bevacizumab, or an irinotecan-containing regimen in combination with an agent targeting the epidermal growth factor receptor (for RAS/BRAF wild-type disease).

Deintensification of adjuvant radiation therapy in human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma

In patients with human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC), there is interest in treatment deintensification strategies, which use less radiation in select patients, while preserving outcomes. In a phase II trial (ECOG 3311), patients with locoregionally advanced HPV-associated OPSCC treated with transoral robotic surgery received adjuvant therapy risk-stratified by postoperative pathology [2]. Among the approximately 200 patients with intermediate-risk disease randomly assigned to lower or standard doses of radiation therapy (RT), lower dose RT had similar two-year disease-free survival and lower rates of treatment-related toxicity. While promising, treatment deintensification remains an investigational approach in HPV OPSCC.

Adjuvant targeted therapy for stage III BRAF-mutant melanoma

For patients with BRAF V600-positive stage III melanoma, the optimal adjuvant strategy is unknown. In a phase III trial (COMBI-AD) in patients with completely resected, BRAF V600-positive stage III melanoma, the combination of the targeted agents dabrafenib and trametinib improved both five-year relapse-free survival (52 versus 36 percent) and distant metastasis-free survival (65 versus 54 percent) at five years, relative to placebo [3]. Overall survival data are immature. Although these results are promising, we continue to suggest adjuvant anti-PD-1 therapy rather than targeted therapy for most patients with resected BRAF-mutant stage III melanoma, pending further data.

First liquid biopsy next generation sequencing diagnostic test approved

While molecular diagnostics have traditionally been performed on biopsies of solid tumor tissue in non-small cell lung cancer (NSCLC), blood-based tests or so-called "liquid" biopsies are gaining popularity. The US Food and Drug Administration has approved a circulating tumor DNA test for lung cancer patients that, for the first time, uses next generation sequencing, evaluating for genetic alterations in 55 genes [4]. However, given limited sensitivity of liquid biopsies, NSCLC patients who test negative for the biomarkers evaluated should undergo tissue biopsy testing, if feasible.

Cancer risks in male BRCA1 versus BRCA2 carriers

A recent cohort study of 6900 male BRCA1/2 carriers suggested differences in the cancer spectrum, with BRCA2 carriers having higher risks of breast, prostate, and pancreatic cancer than BRCA1 carriers but lower risk of colorectal cancer [5]. However, further data are needed to confirm these differences. Our approach to breast cancer surveillance is the same for male BRCA1 and BRCA2 carriers, and includes regular breast clinical and self-examination, with consideration of annual mammography in men with gynecomastia; by contrast, we recommend prostate cancer screening starting at age 40 years for BRCA2 carriers, while for BRCA1 carriers, this is optional.

1. Tang W, Ren L, Liu T, et al. Bevacizumab Plus mFOLFOX6 Versus mFOLFOX6 Alone as First-Line Treatment for RAS Mutant Unresectable Colorectal Liver-Limited Metastases: The BECOME Randomized Controlled Trial. J Clin Oncol 2020; 38:3175.

2. Ferris RL, Flamand Y, Weinstein GS, et al. Transoral robotic surgical resection followed by randomization to low- or standard-dose IMRT in resectable p16+ locally advanced oropharynx cancer: A trial of the ECOG-ACRIN Cancer Research Group (E3311). J Clin Oncol 2020; 38 (suppl):6500.

3. Dummer R, Hauschild A, Santinami M, et al. Five-Year Analysis of Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma. N Engl J Med 2020; 383:1139.

4. US Food and Drug Administration (FDA). FDA Premarket Approval: Next-generation sequencing oncology panel, somatic or germline variant detection system. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=p200010 (Accessed on August 14, 2020).

5. Silvestri V, Leslie G, Barnes DR, et al. Characterization of the Cancer Spectrum in Men With Germline BRCA1 and BRCA2 Pathogenic Variants: Results From the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). JAMA Oncol 2020; 6:1218.

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