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Precision Oncology Briefs: Cutting Breast Cancer Deaths; Enfortumab Vedotin; Rare CRC Mutations


A meta-analysis showed adding trastuzumab to chemotherapy for the treatment of early-stage, HER2-positive breast cancer could cut deaths worldwide; a researcher discusses the promise of enfortumab vedotin for advanced urothelial cancers; more research is needed in rare genomic alterations in subsets of colorectal cancer (CRC).

Researcher Highlights Promise of Enfortumab Vedotin for Advanced Urothelial Cancers

In a recent interview with Targeted Oncology™, Thomas Powles, MD, MBBS, MRCP, a professor of genitourinary oncology, director of the Bart Cancer Centre, and lead for Solid Tumour Research at Cancer Research UK, discussed the latest research around enfortumab vedotin in locally advanced or metastatic urothelial cancer.

Enfortumab vedotin (Padcev) was approved by the FDA last month for patients with locally advanced or metastatic urothelial cancer who had previous treatment with a PD-1/PD-L1 inhibitor as well as with platinum-based chemotherapy; are ineligible for cisplatin-containing chemotherapy; and have previously received 1 or more prior lines of therapy.

Powles noted that enfortumab vedotin, an antibody-drug conjugate targeting NECTIN-4, which is expressed on the vast majority of urothelial cancers, is expected to replace the standard-of-care chemotherapy and called it “practice-changing.” The drug has a response rate of about 40%, he said.

Trastuzumab Plus Chemotherapy Could Reduce Early-Stage HER2-Positive Breast Cancer Deaths by a Third

A recent study reviewed how the addition of trastuzumab to chemotherapy for the treatment of early-stage, HER2-positive breast cancer can reduce disease recurrence and potentially cut mortality from breast cancer by a third worldwide.

The Targeted Oncology™ report about the Lancet Oncology meta-analysis said there was a highly statistically significant connection between the use of trastuzumab and chemotherapy on the reduced risk of recurrence and mortality compared to chemotherapy alone (RR, 0.66; 95% CI, 0.62-0.71; P <.0001). The average 10-year reduction in risk of recurrence for the combination was 9% (95% CI, 0.4 -10.7; P <.0001) with a 6.4% (range, 4.9% to 7.8%) reduction in 10-year breast cancer mortality. The all-cause mortality risk was reduced by 6.5% (range, 5.0%-8.0%). There was no increase in death without recurrence.

The meta-analysis included 13,864 participants with early-stage, HER2-positive breast cancer who were randomized to receive either chemotherapy plus trastuzumab or chemotherapy alone in 7 relevant trials between February 2000 and December 2005.

More Research Needed in Rare Genomic Alterations of CRC

In a recent interview and podcast, Michael Overman, MD, a professor in the Department of Gastrointestinal Medical Oncology at the University of Texas MD Anderson Cancer Center, discussed targeted rare genomic alterations in subsets of colorectal cancer (CRC). The conversation with Targeted Oncology™ touched on recent advances in treatment and testing, the genomic alterations that are the most challenging to treat, and areas of promising future research.

Despite the approval of some drugs for mutations in CRC, there is still a treatment gap for these patients; Overman said research is needed in biomarkers like mismatch repair deficiency and microsatellite instability. Some of the more challenging situations to treat include CRC mutations of KRAS G12C, BRAF V600E, and BRAF nonV600E, he said.

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