Ragini Kudchadkar, MD, chair of the Clinical and Translational Review Committee at Winship Cancer Institute, as well as an associate professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine, discusses future research directions for patients with rare, non-melanoma skin cancers. 

There is a great interest in studying rare skin cancers, such as advanced basal cell carcinoma and squamous cell carcinoma, as these cancers can cause significant mortality for patients, Kudchadkar explains. Understanding which patients respond to treatment and who will experience durable responses is an area of focus for future research efforts, Kudchadkar adds.

Investigators also seek to determine whether PD-1 inhibitors will become a frontline treatment option for those with basal cell carcinoma, as well as whether hedgehog inhibitors will provide durable responses in this patient population, Kudchadkar concludes. 

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Ragini Kudchadkar, MD, discusses future research directions for patients with rare, non-melanoma skin cancers. 

Dr. Kudchadkar on Future Research Directions for Rare, Non-Melanoma Skin Cancers 

Ragini Kudchadkar, MD, chair of the Clinical and Translational Review Committee at Winship Cancer Institute, as well as an associate professor, Department of Hematology and Medical Oncology at Emory University School of Medicine, discusses the durability of immunotherapy in non-melanoma skin cancers.

For Merkel cell carcinoma, there has been durability of responses observed with immunotherapy agents. For example, a study looking at pembrolizumab (Keytruda) in this patient population showed that the vast majority of patients who responded to the PD-1 inhibitor continued to experience response, Kudchadkar explains.

In basal cell carcinoma and squamous cell carcinoma, however, the durability of immunotherapy agents has not yet been identified. Investigators remain optimistic based on durability with immunotherapy seen in other skin cancers, though longer follow-up is needed to say for certain, Kudchadkar concluded.

Ragini Kudchadkar, MD, discusses the durability of immunotherapy in non-melanoma skin cancers.

Dr. Kudchadkar on the Durability of Immunotherapy in Non-Melanoma Skin Cancers

Ragini Kudchadkar, MD, assistant professor, Department of Hematology and Medical Oncology, associate director, Hematology and Medical Oncology Fellowship Program-Clinical/Service, Emory University School of Medicine, Winship Cancer Institute, discusses immunotherapy in Merkel cell carcinoma.

Merkel cell carcinoma has traditionally been treated with chemotherapy, says Kudchadker. The discovery of Merkel cell polyomavirus led to the development of immunotherapy, as it allows for clinicians to see PD-L1 staining and exhausted T cells.

Pembrolizumab (Keytruda), nivolumab (Opdivo), and avelumab (Bavencio) are all used for the treatment of Merkel cell carcinoma, and are demonstrating durable responses previously unseen in this disease.

Avelumab was approved by the FDA in March 2017 based on the data from the phase II JAVELIN Merkel 200 study. In the open-label trial, the objective response rate (ORR) with avelumab was 33% (95% CI, 23.3%-43.8%), which included an 11.4% (95% CI, 6.6%-19.9%) complete response rate and a 21.6% (95% CI, 13.5%-31.7%) partial response rate. 

Ragini Kudchadkar, MD, assistant professor, Department of Hematology and Medical Oncology, associate director, Hematology and Medical Oncology Fellowship Program-Clinical/Service, Emory University School of Medicine, discusses immunotherapy in Merkel cell carcinoma.
 

Dr. Kudchadkar on Immunotherapy in Merkel Cell Carcinoma

Ragini Kudchadkar, MD, assistant professor, Department of Hematology and Medical Oncology, associate director, Hematology and Medical Oncology Fellowship Program-Clinical/Service, Emory University School of Medicine, discusses the FDA approval of avelumab for the treatment of patients with Merkel cell carcinoma.

Dr. Kudchadkar on the FDA Approval of Avelumab in Merkel Cell Carcinoma

Ragini Kudchadkar, MD, assistant professor, medical oncology, Moffitt Cancer Center, discusses the potential for combining therapies for the treatment of melanoma.

Kudchadkar believes that combination therapy is the future of melanoma treatment, especially with immunotherapies. In melanoma, Kudchadkar says, there remains a need for patients to respond quickly and maintain long-term benefit.

The combination of ipilimumab and nivolumab, of which data was presented at the 2013 ASCO Annual Meeting, demonstrated tumor reduction in about 80% of patients, Kudchadkar says. Though this is exciting, it is worth noting that many patients had to discontinue treatment because of toxicity. Kudchadkar says there is a need for a larger population study in order to get a clearer toxicity profile of this drug combination when used to treat patients with melanoma.

Dr. Kudchadkar on Combining Therapies for Melanoma

Ragini Kudchadkar, MD, assistant professor, medical oncology, Moffitt Cancer Center, discusses testing for melanoma.

If a patient with melanoma is not on a clinical trial, Kudchadkar says, they need to be tested to see if they have a chance to benefit from a targeted therapy. Though 

mutational status is typically looked at in patients with stage IV disease, most physicians believe that a high-risk patient with stage III disease should also be tested. This population of patients has a high risk of recurrence, Kudchadkar says, sometimes as high as 70%. Kudchadkar says she does not recommend testing patients with early stage disease, as they can be cured with surgery alone.

Dr. Kudchadkar Discusses Melanoma Testing

Ragini Kudchadkar, MD, assistant professor, medical oncology, Moffitt Cancer Center, discusses the benefits of combining BRAF and MEK inhibitors when treating melanoma.

Early data demonstrated that the combination of BRAF and MEK inhibitors improve outcomes compared with single agents in patients with melanoma, Kudchadkar says.

If only one pathway is blocked, Kudchadkar says, the cancer cell figures out how to overcome the blockage with time. By combining the agents, the mechanism of resistance from the cancer cell is blocked. This allows patients to stay on therapy longer and decreases skin toxicities that are seen in single agent use.

Kudchadkar believes that it is likely that the combination will become the next standard of care.

Ragini Kudchadkar, MD

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