Mark E. Robson, MD, chief, Breast Medicine Service, Memorial Sloan Kettering Cancer Center, discusses the potential utility of tucatinib in the treatment of patients with HER2-positive breast cancer.

In February 2020, the FDA granted a priority review designation to a new drug application (NDA) for tucatinib for use in combination with trastuzumab (Herceptin) and capecitabine (Xeloda) for the treatment of patients with unresectable locally advanced or metastatic HER2-positive breast cancer, including patients with brain metastases, following ≥3 prior lines of HER2-directed agents separately or in combination, in the neoadjuvant, adjuvant, or metastatic setting.

The utility of tucatinib could be influenced by that of neratinib (Nerlynx), explains Robson. In February 2020, the FDA approved a supplemental NDA for neratinib for use in combination with capecitabine for the treatment of patients with advanced or metastatic HER2-positive breast cancer who received ≥2 prior anti—HER2-based regimens in the metastatic setting.

While there has not been a head-to-head trial with the agents, tucatinib could have greater utility in patients with brain metastases, says Robson. Additionally, tucatinib appears to be better tolerated.

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Mark E. Robson, MD, discusses the potential utility of tucatinib in the treatment of patients with HER2-positive breast cancer.

Dr. Robson on the Potential Utility of Tucatinib in HER2+ Breast Cancer

Mark E. Robson, MD, chief, Breast Medicine Service, Memorial Sloan Kettering Cancer Center, discusses the application of precision medicine in breast cancer.

Ideally, every treatment should be grounded in precision medicine, says Robson. Currently, precision medicine is understood through a patient’s genomic profile. In breast cancer, that understanding has led to tailored treatment for patients with homologous recombination deficiencies and 

For example, women and men who have germline 

 mutations are known to derive benefit from PARP inhibitors. Additionally, patients who develop somatic 

 mutations are likely to respond to the PI3K inhibitor alpelisib (Piqray). As such, it has become common practice to use genomic profiling to inform clinical decisions, particularly in the first-line metastatic setting, concludes Robson.

Dr. Robson on the Application of Precision Medicine in Breast Cancer

Mark E. Robson, MD, chief, Breast Medicine Service, Memorial Sloan Kettering Cancer Center, discusses the importance of educational efforts aimed at understanding the differences between biosimilars and biologics in oncology.

Educational efforts regarding the development and approval process for biosimilars could help reduce the skepticism that is associated with these agents, says Robson. 

Regulatory pathway differences between biosimilars and originator compounds are often misunderstood. Explanation of the biosimilar approval process could help clarify these differences and shed light on the current criteria that are used to demonstrate similarity between these agents, concludes Robson.

Mark E. Robson, MD, discusses the importance of educational efforts aimed at understanding the differences between biosimilars and biologics in oncology.
 

Dr. Robson on Differences Between Biosimilars and Biologics in Oncology

Mark E. Robson, MD, chief, Breast Medicine Service, Memorial Sloan Kettering Cancer Center, discusses the driving force behind biosimilar use in oncology.

Biosimilars are going to be an integral component of treatment in the future, says Robson. Notably, the decision of whether to prescribe a biosimilar or a biologic is going to be driven by payers, he adds. In breast cancer, several biosimilars have already received regulatory approval. As such, certain payers are already requiring that the trastuzumab biosimilar be used over the biologic if HER2-targeted therapy is mandated.

Although the data that have been reported have shown the equivalency of approved biosimilars and biologics, there is still some hesitancy in the community regarding their use. However, as biosimilars gain more traction in the field and provider confidence grows, these agents are going to result in a paradigm shift, concludes Robson.

Dr. Robson Discusses the Driving Force Behind Biosimilar Use in Oncology

Mark E. Robson, MD, chief, Breast Medicine Service, Memorial Sloan Kettering Cancer Center, discusses the toxicity profile of olaparib (Lynparza) in breast cancer.

The OlympiAD trial randomized 302 patients with HER2-negative, germline 

mutated metastatic breast cancer to receive 300-mg olaparib tablets twice daily or treatment of physician’s choice. Across the entire trial, the median progression-free survival was 7.0 months with olaparib and 4.2 months for physician's choice of therapy (HR, 0.58; 95% CI, 0.43-0.80; 

There were some toxicities associated with olaparib. Robson says that there were relatively low grade 3 toxicities, a fair amount of low-grade nausea, some cytopenia, and myelosuppression. The most significant toxicity was the 16% rate of grade 3 anemia, says Robson, which led to 18% of patients to receive a transfusion.

Mark E. Robson, MD, chief, Breast Medicine Service, Memorial Sloan Kettering Cancer Center, discusses the toxicity profile of olaparib (Lynparza) in breast cancer.
 

Dr. Robson on the Toxicity Profile of Olaparib in Breast Cancer

Mark E. Robson, MD, chief, Breast Medicine Service, Memorial Sloan Kettering Cancer Center, discusses an exploratory analysis of the OlympiAD trial for patients with HER2-negative breast cancer with a germline 

 mutation. Robson highlighted these findings in an interview with 

 during the 35th Annual Miami Breast Cancer Conference.

OlympiAD was a randomized phase III trial of olaparib compared with conventional chemotherapy in patients with HER2-negative breast cancer who harbored 

 mutations. Results showed that there was a statistically improvement in progression-free survival (PFS). Preservation of quality of life is also seen across subsets, Robson says.

One question following the study, he explained, was whether patients have more of a benefit with olaparib if they have more disease versus less disease. In the exploratory analysis, researchers investigated the PFS in patients who had 1 metastatic site versus more than 1 site. Findings showed that there were similar degrees of benefit in each group.

In those with 1 metastatic site, the median PFS with olaparib was 8.4 months compared with 4.2 months with physician's choice of therapy (TPC; HR, 0.62; 95% CI, 0.35-1.13). In patients with ≥2 metastatic sites, the median PFS was 6.5 months with olaparib compared with 3.0 months for TPC, which crossed the barrier for statistical significance (HR, 0.59; 95% CI, 0.43-0.82).

These data show that patients with more disease burden do not need to receive chemotherapy and can still be treated with a PARP inhibitor, Robson concludes.

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Mark E. Robson, MD, chief, Breast Medicine Service, Memorial Sloan Kettering Cancer Center, discusses an exploratory analysis of the OlympiAD trial for patients with HER2-negative breast cancer with a germline BRCA1/2 mutation.

Dr. Robson on Exploratory Analysis From OlympiAD in Breast Cancer

Mark E. Robson, MD, Clinic Director, Clinical Genetics Service, Memorial Sloan Kettering Cancer Center, discusses managing breast cancer risk.

There are other mutations and genes that can increase breast cancer risk besides BRCA1 and BRCA2. These mutations should be managed differently, said Robson His team has developed a framework to provide oncologists with information about these new genes.

Another issue regarding breast cancer risk management surrounds discussing with patients whether or not they need to undergo preventative surgery, such as a mastectomy. This has become more commonly accepted in the United States, said Robson.

Preventative surgery may make sense for some women with a high-risk of breast cancer. However, oncologists do need to balance a patient’s desire to have surgery for peace-of-mind with their risk level, said Robson.

Mark E. Robson, MD

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