Melanoma Tissue
Researchers at The University of Texas MD Anderson Cancer Center have found that a rare resistance mutation first thought to appear in melanoma (pictured) following treatment with a targeted therapy has instead turned out to be hiding in the tumor all along. [Definiens]

Exploratory analyses of data from the SWOG S1801 clinical trial of pembrolizumab in advanced melanoma shows researchers observed major pathological response exceeding 50% in patients with stage III-IV resectable disease. The results were presented Monday at the European Society of Medical Oncology (ESMO) Congress 2023 in Madrid, by Sapna P. Patel, MD, chair of the SWOG melanoma committee and associate professor of melanoma medical oncology at the University of Texas MD Anderson Cancer Center.

“The pathologic responses seen in S1801 highlight the potential for single-drug immunotherapy to achieve results that we know are important for individual patient outcomes, namely the demonstration of a favorable pathologic response after a few doses of treatment,” Patel said.

Patel urged caution against over-interpretation of these results, noting that the absence of a pathologic response should not be seen as a lack of benefit.

“The absence of a pathologic response means there is room for improvement, but those patients still likely benefitted from a neoadjuvant approach with immunotherapy where their immune system began priming with tumor in situ than if they had gone to upfront surgery,” Patel noted. “The goal of a short duration of neoadjuvant immunotherapy is to initiate tumor priming, not necessarily to shrink the tumor(s) or demonstrate pathologic response. Even in the absence of a radiographic or pathologic response, a patient’s immune system may have a more amplified and diversified response after a few doses of pre-operative immunotherapy, and then the tumor can be resected.”

Pathologic response assessment involves examining surgical tissue to determine whether actively growing cancer cells, known as residual viable tumor, are present. A complete pathologic response indicates the absence of active cells, while a near-complete response involves active cancer cells comprising one to ten percent of the tumor bed. A “major pathologic response” encompasses both these categories, with no more than 10% residual viable tumor.

However, the assessment of pathologic response is not without its challenges. Pathologists make estimates based on histologic clues, and the tumor’s original size before neoadjuvant therapy is often unclear, potentially leading to underestimations. Also, the physical size of the glass slides can also provide challenges as they can only hold a fraction of the lymph node specimens. This causes a mathematical artifact if a 5-cm matted lymph node is sectioned across multiple glass slides.

In S1801, a total of 135 patients who underwent surgery were treated with neoadjuvant pembrolizumab. From this group, 105 specimens were submitted for central review for pathologic response, the vast majority of which were lymph node specimens. Reviews of all the specimens were performed by Victor G. Prieto, MD, PhD, the Ferenc and Phyllis Gyorkey Chair for Research and Education in Pathology at the University of Texas MD Anderson Cancer Center. When Prieto conducted the review, he had no information on the clinical outcomes of the patients whose specimens were examined.

“Particularly interesting was the observation that there was different distribution of response to the treatment (amount of necrosis) among different lesions and even different areas in the same patient,” Prieto said. “This suggests the existence of different tumor phenotypes in the same patient.”

The study also explored the correlation between pathologic response and recurrence-free survival (RFS). Patients whose tumor(s) achieved a pathologic complete response had an RFS rate of 89% at 24 months.

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