SWOG S1801 Trial: Pembro After or Before Surgery? [2022]

It is not yet known which type of immunotherapy, adjuvant or neoadjuvant, is more effective in the treatment of high-risk melanoma; this question has not been answered. The findings of this trial provide additional evidence regarding the conditions under which one approach might be more beneficial than the other. 

It has been demonstrated that neoadjuvant immunotherapy can induce spectacular complete pathologic responses, which, up until this point, have been associated with a sustainable response. Patients with clinically detectable high-risk melanoma (that have received prior radiation therapy) are more likely to have a positive response to checkpoint inhibitors can be detected through neoadjuvant therapy, which then makes it feasible to lessen the severity of the treatment. This is one of the potential benefits of using neoadjuvant therapy.

What Did These Data Say About The SWOG S1801 Clinical Trial?

This phase II randomized study (patients randomized with clinically detectable high-risk melanoma that have received prior radiation therapy) adds to the growing body of information that suggests neoadjuvant immunotherapy may be more successful in treating clinically detectable cancer than adjuvant immunotherapy. Even in cases of metastatic melanoma, it is possible to detect exceptional complete responses to treatment; nevertheless, a consensus has not yet been reached regarding the optimal timing of treatment for the resectable disease (no prior resection). 

“SWOG S1801 shows that NAT followed by surgery is a safe and feasible strategy. CPR rates are similar to those previously observed in a similar setting and not distant from the CR rates observed in the metastatic setting with anti-PD-1 monotherapy. The early improvement of EFS with NAT compared to AT is highly promising. Overall, these early positive results warrant further OS follow-up and additional phase 3 investigations to understand whether NAT is a new standard of care for patients with stage IIIB-IV resectable melanoma. Positive results may lead to the implementation of NAT straight away.” Marco Donia, National Center for Cancer Immune Therapy (CCIT-DK), Copenhagen University Hospital, Herlev, Denmark

What Are The Next Steps For The SWOG S1801 Clinical Trial?

The authors provide more evidence of the efficacy and utility of neoadjuvant therapy in treating patients with high-risk illnesses. They are an addition to the list of benefits that might be found with the immediate use of checkpoint inhibitors before surgery and while there is still a bulky tumor in the body. Although we do not yet have the answer to the question, we do not yet have the answer to that question. 

Again, the evidence we have suggests that this is not the case regarding immune therapy. It is essential that you keep this in mind since we do not want the results of any curative surgery to be negatively impacted by any neoadjuvant therapy. On the other hand, there is evidence to suggest that this is not the case with immunological therapies.

“We will need further survival data to change the standard of practice in high-risk melanoma and demonstrate whether there is a superior sequence of therapy and surgery.” Maya Dimitrova, MD, medical oncologist at NYU Langone Perlmutter Cancer Center

What Are The Strengths And Limitations Of The SWOG S1801 Study?

This well-designed study makes an effort to solve a challenging topic about the order in which systemic therapy and surgery should be carried out. Long-term (event free) survival statistics will be necessary, however, to properly evaluate the advantages and disadvantages of a particular therapy sequence compared to others. 

“It's not just what you give, it's when you give it! SWOG S1801 demonstrates that the same treatment for resectable melanoma given in a different sequence can generate lower rates of melanoma recurrence.” said study first author Sapna Patel, The University of Texas MD Anderson Cancer Center, Houston, USA. “In this case, we used the immune checkpoint inhibitor pembrolizumab. This treatment relies on the presence of pre-existing T cells that encounter cancer cells to generate a larger immune response before the melanoma is removed, and with it the bulk of tumor-specific T cells thrown away, than if given after surgery. Our study noted an improvement in event-free survival in the neoadjuvant arm compared to the adjuvant arm. Importantly, a similar number of patients in both arms experienced (adverse) events before initiating adjuvant pembrolizumab, but the rate of (adverse) events after adjuvant therapy was higher (worse) in the adjuvant arm. The findings from S1801 have important implications about the sequence of treatment for patients with melanoma and other cancers that respond to immune checkpoint blockade.”

About the SWOG S1801 Clinical Trial

This study will be critical in determining the characteristics of patients and tumors that show a positive response to checkpoint inhibitors and biomarkers that indicate such a response. In addition, it could be helpful in identifying individuals who can avoid prolonged exposure to the medicine and, as a result, the risk of immune-related side effects that would follow.

Maya Dimitrova, MD - About The Author, Credentials, and Affiliations

Her parents are internists, and both of her grandparents were physicians. As a child, she was amazed by her parents' expertise in assisting their patients and their enduring ties with them. Some forms of cancer are now chronic diseases that are controllable due to scientific progress. She chose to study medical oncology (melanoma medical oncology) to help patients with these disorders and provide the best care possible.

At the Perlmutter Cancer Center at NYU Langone, she specializes in treating patients with melanoma as well as breast, colon, lung, and genitourinary cancers. To provide individualized care, she does genetic and molecular tumor (cells) profiling, which entails analyzing a tumor to establish its unique characteristics and the optimal treatment. She prescribes a mix of targeted medications and immunotherapy, which may be more successful and have fewer adverse effects than chemotherapy.

Her objective is to provide patients with access to the most advanced cancer treatments in medical oncology. Her research on the most effective pharmaceutical combinations and forecasts which patients will respond best to them. She offers her patients access to a multidisciplinary team of social workers, dietitians, psychologists, and psychiatrists to provide the most comprehensive care possible.

It is essential to develop a relationship of trust with patients. Therefore, she endeavors to get to know them and offer the type of treatment she would want to receive. When interacting with patients, she is straightforward and honest. She describes the individual's prognosis, potential therapy side effects, and what they may and cannot anticipate from treatment. In addition, she never presumes to know a patient's desires. Together, we decided on a therapy plan after She described all the treatment choices.

Relieving a patient's anxiety and fear regarding their diagnosis is gratifying. She wants to give them hope because she and her colleagues can do so much to assist.