Advancing Care in Locally Advanced HNSCC: Integrating Perioperative Immunotherapy and Multimodal Strategies

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Dr. Adkins:
This is CE on ReachMD, and I'm Dr. Douglas Adkins. Let's start our discussion by looking at a case.A 57-year-old male presented with right jaw pain, difficulty opening mouth, and weight loss. The patient had no significant past medical history but was known to be a significant smoker over the years.

On physical exam, the patient's performance status was 0. Patient had notable trismus and a very large ulcerative right buccal lesion that extended into the right retromolar trigone and the mandibular alveolar ridge. The neck exam revealed a mobile 3- to 4-cm right level 1B lymph node. Laboratory studies showed normal organ function and blood counts. A biopsy of the right buccal lesion revealed HPV-negative squamous cell carcinoma. The tumor PD-L1 combined positive score was 20.

On referring the appropriate staging of this patient, one uses the AJCC 8th Edition Staging System. This patient has a T3 tumor, defined as that over 4 cm, and N2a disease, defined as metastases in a single ipsilateral lymph node larger than 3 cm but smaller than 6 cm. 

The standard of care for patients with T3N2 disease is surgery, preferably. And patients are recommended to have a resection of the primary tumor and neck dissection.

This patient was presented in a multidisciplinary tumor board, and the recommendation was surgery using a composite resection, along with a right partial maxillectomy and bilateral neck dissections and reconstruction using radial forearm free flap. 

Also, adjuvant radiotherapy or chemoradiotherapy was recommended, with the determination of the addition of chemotherapy based on the presence or absence of high-risk pathology. The patient was offered the opportunity to participate in the KEYNOTE-689 clinical trial, agreed to participate, signed consent, and was enrolled and was randomized to receive perioperative pembrolizumab plus standard of care.

This slide shows you the impact of 2 doses of pembrolizumab administered before surgery. On clinical exam, there was a notable reduction in the size and extent of the right buccal lesion. And on the 2 slides on the left panel, one can see a reduction in the thickness of the right buccal lesion on radiologic imaging. On the right 2 X-rays, one can see a reduction in the neck node. This patient did experience an asymptomatic rise in TSH, signaling immune therapy–induced subclinical hypothyroidism.

The pathology of the surgical specimen showed multifocal squamous cell carcinoma at the primary site over a bed area of 4.1 cm, with a depth invasion of 5 mm. There was no lymphovascular or perineural invasion, and importantly, the surgical margins were negative. There was evidence under the microscope of pathological tumor response to the immunotherapy. The neck dissection in the right neck showed 2 of 53 positive nodes, largest 9 mm, and importantly, no extranodal extension. All lymph nodes in the left neck did not show cancer. So the pathologic stage was T2N2b, and that is, this patient has intermediate-risk pathology.

This patient did have adverse pathologic features, but not high-risk pathology. This patient had intermediate-risk pathology that is coded as other risk features here, and therefore, this patient should receive post-op adjuvant radiotherapy. On the clinical trial, the patient did indeed receive post-op adjuvant radiotherapy along with 3 cycles of concurrent pembrolizumab, followed by 12 cycles of adjuvant pembrolizumab. 

This patient is now nearly 5 years out from completion of treatment and has had no evidence of recurrent disease.

It's important to note that the results of the KEYNOTE-689 trial showed an improvement in event-free survival with the addition of pembrolizumab to standard of care in patients with resectable locally advanced head and neck cancer. And the FDA has now approved the addition of perioperative pembrolizumab to standard of care in patients with resectable locally advanced head and neck cancer that has a PD-L1 CPS score of 1 and greater.

With that, my time is up. I hope you found this quick case review helpful. Thanks so much for listening.

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