The silver lining for patients experiencing side effects related to immunotherapy and targeted therapy for cancer treatment is that these effects are an indication of effective treatment. Not everyone responds to anti-cancer therapy, but those who do may exhibit it in very visible ways.
This phenomenon was observed in patients with cancer who experienced acne-like rashes from EGFR inhibitors or vitiligo after successful treatment with immunotherapy. Now, a new study confirms this principle in triple-negative breast cancer. Until recently, no one had assessed whether patients being treated for triple-negative breast cancer experienced negative impacts during neoadjuvant therapy using immune checkpoint inhibitors if they were responding well. Researchers at the Yale Cancer Center decided to investigate.
Using a small group of 67 patients, they found that patients who experienced an immune-related adverse event (irAE) did better in several measurements compared to those without any irAEs. For example, the 48-month overall survival rate was 92% for patients with triple-negative breast cancer who developed an irAE versus 78% for those patients who did not develop an irAE.
Some patients develop more than one irAE, which might otherwise be considered unlucky. However, when the number of irAEs was analyzed by the researchers, those patients experiencing more than one irAE achieved a 100% event-free survival rate. Patients who did not experience any irAEs achieved a 66% event-free survival rate in 48 months.
Similarly, although the overall survival rate over 48 months was 92% for patients who developed an irAE, it increased to 100% for patients experiencing more than one irAE. The data shows detecting irAEs can provide an early indication of patient outcomes.
The most frequent irAEs experienced by the patients were dermatologic, manifesting as eczema, folliculitis, hyperpigmentation, lichenoid dermatitis, psoriasis exacerbation, and rash. Endocrine irAEs, such as adrenal insufficiency, diabetes, hypothyroidism, thyroiditis, and subclinical hypothyroidism, were the next most common manifestations of irAEs.
A pathological complete response was achieved among 56% of patients who developed an irAE, compared to 40% in those without an irAE. In contrast, the patients who had the poorest outcomes had residual cancer and did not develop any irAEs.
Interestingly, the researchers isolated tumor-infiltrating lymphocytes from 55 patients out of 67. Those patients with an irAE more frequently exhibited high stromal tumor-infiltrating lymphocytes, which is defined as >30%. Patients who did not develop any irAEs had an average of 21% stromal tumor-infiltrating lymphocytes, with a range between 13% and 28%.
Taken together, the study again exemplifies a crucial principle entwined with the side effects of immunotherapy. Patients who will respond well to treatment are also more likely to exhibit one or more irAEs. The unfortunate lesson is for patients manifesting irAEs is that they have inadvertently provided clinicians with a biomarker indicating the best outcomes.
Reference: This summary is based on the article by Rioss-Hoyo A, Dai J, Noel T et al. “Immune-related adverse events are associated with better event-free survival in a phase I/II clinical trial of durvalumab concomitant with neoadjuvant chemotherapy in early-stage triple-negative breast cancer” published in ESMO Open in 2025.
