Skin-related side effects of a certain cancer treatment may indicate stronger responses, survival

Patients who develop skin side effects as a result of immune checkpoint inhibitors may have a stronger response to cancer treatment and may indicate a survival advantage over those who did not develop these side effects. according to the results of a recent study.

Although this benefit was particularly accentuated in patients with melanoma, it was also evident in patients with malignant neoplasms of the digestive organs, urinary tract and bronchi or lungs.

“The implications of (these) data suggest that skin (or skin-related) toxicities may be beneficial in the setting of immunotherapy,” said Dr. Yevgeniy R. Semenov, instructor in dermatology at Massachusetts General Hospital and Harvard Medical School in Boston. , in an interview with CURE®. “While they can be distressing for patients, the glass isn’t necessarily half empty here. There may be a silver lining on the other side to have them developed.

Use of immune checkpoint inhibitors

There has been a substantial increase in the use of immune checkpoint inhibitors to treat advanced cancers, including breast cancer melanoma, Semenov explained, with up to 250,000 patients eligible for this therapy in the States. United per year.

“Despite their survival benefits, these drugs have significant immune system-related toxicities that contribute to morbidity and, in some cases, may also contribute to mortality,” Semenov said. “It’s a double-edged sword, where the drug is great, but the toxicity really needs to be understood and managed appropriately without affecting the benefits of the drug itself.”

Semenov added that skin-related side effects are most common in patients treated with immunotherapy and often occur early in immunotherapy.

“(This) gives us a very unique opportunity to decide whether or not immunotherapy works, or whether the harm outweighs the good at a very early stage of therapy,” he said.

To examine the potential implications of skin-related side effects on survival outcomes, Semenov and colleagues analyzed data from 7,008 patients treated with immune checkpoint inhibitors for malignant neoplasms of melanoma, bronchus/lungs , digestive organs or urinary tract. It should be noted that all patients in this study developed skin-related side effects as a result of their treatment. These patients were matched with 7,008 cancer patients who did not develop skin-related side effects.

Study results demonstrated that developing skin toxicities as a group resulted in a 20% survival benefit in immunotherapy recipients. Several types of skin-related side effects were significantly protective against mortality, including psoriasis, lichen planus/lichenoid dermatitis (an inflammatory skin condition), itching in the absence of a rash, and broad category of non-specific rashes. Several other skin-related side effects have demonstrated clinically significant effects such as vitiligo (when the skin sheds pigment cells in patches), Grover’s disease (a skin disorder with small, raised lesions on the chest and back) and bullous pemphigoid (a skin condition with large blisters on areas of the body that often sag like the upper thighs and lower abdomen), but did not reach statistical significance.

“We found that the morphology of toxicity can be important,” Semenov said. “Not all skin toxicities are created equal. We have found that patients who develop toxicities that resemble lichen planus, which is an inflammatory skin disease; toxicities that resemble vitiligo, which is a depigmenting disease of the skin; as well as toxicities that resemble psoriasis actually tend to have better survival outcomes than other toxicities like mucositis (inflammation and pain in the mouth or gut), for example. The type of rash you get is important, and why this is the case is yet to be elucidated.

Further research needed

Semenov hypothesized that why some of these side effects have a favorable association with survival over others may be related to the management of side effects, which sometimes require systemic immunosuppression which can limit the antitumor effect of immunotherapy. For example, vitiligo is not often treated with systemic immunosuppression, which allows the patient to “benefit from immunotherapy without diminishing the effectiveness of immunotherapy by taking an immunosuppressive drug to treat skin toxicity”, a he declared. In contrast, side effects such as bullous pemphigoid are more distressing to the patient due to the extreme itching and extent of the rash, which usually requires the use of systemic immunosuppressive drugs and may even lead to suspension. or even when immunotherapy is stopped.

While these results are “very encouraging,” according to Semenov, several questions remain for both patients and clinicians.

“What do you do once serious toxicity develops? Should we stop immunotherapy, or do we see this as a really favorable prognostic marker that actually tells us, “Hey, keep it up, we’re fine,” Semenov added. “We need to find a way to effectively treat these (skin-related side effects) while continuing with immunotherapy. Conversely, if we don’t get any toxicity, is that a warning sign that the drug isn’t not as effective against cancer? Should we consider a stronger treatment regime? These are all very important questions for patients and clinicians, but it is too early to say what weight to give to these data.

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