Neoadjuvant IO Yields Deep Responses in Head and Neck Cancer

Neoadjuvant IO Yields Deep Responses in Head and Neck Cancer

Preoperative checkpoint inhibition led to deep responses in select patients with head and neck squamous cell carcinoma (SCC) with mostly human papillomavirus (HPV)-negative disease, a small, single-arm study found.

Among 29 evaluable patients included in the IMCISION trial, 31% achieved a near pathologic complete response (pCR) when treated with two courses of anti-PD-1 nivolumab (Opdivo) with or without ipilimumab (Yervoy), a CTLA-4-directed immune checkpoint inhibitor, reported Lotje Zuur, MD, PhD, of the Netherlands Cancer Institute in Amsterdam.
Patients achieving near pCR, defined as primary tumor shrinkage of at least 90%, had a 14-month recurrence-free survival (RFS) rate of 100%, she said at the 2020 European Society for Medical Oncology (ESMO) virtual congress.
This survival benefit was significantly greater than patients with lesser responses in the study, which included another 31% of patients with responses ranging from 20% to 89%, as well as a historical cohort of more than 100 patients treated with extensive surgery (P

“Seventy percent of head and neck cancer patients present with advanced-stage disease and need for high intensive standard of care with a relatively poor overall survival,” said Zuur, highlighting the need for more effective and less “mutilating” strategies.
In some patients, responses were seen at the primary site but not in the lymph nodes, while sometimes the reverse played out.
“Whether these are true immune responses or a delayed response to immunotherapy that would show with increased courses of [immune checkpoint blockade] we do not know at this point of time,” said Zuur. She noted that this is of clinical importance, as future trials may be designed to study de-escalation in patients with a near pCR after neoadjuvant checkpoint blockade.
“The IMCISION regimen of nivolumab with or without ipilimumab is safe and an effective neoadjuvant regimen,” Zuur concluded.
Percentage change in total lesion glycolysis on FDG-PET identified patients with a near pCR, she said.
Translational research from the trial showed that combined positive score, tumor mutational burden, and pretreatment hypoxia gene expression did not predict response to therapy. On-treatment decreases in hypoxia gene expression, however, and on-treatment increases in endothelial cells were both correlated with major pathologic responses, and pretreatment COSMIC AID/APOBEC mutational signatures were enriched in patients with near pCRs.
Researchers also found increased CD8- and CD3-positive cells in these excellent responders, though she cautioned that this was not corrected for multiple testing.
For context, ESMO-invited discussant Christian Simon, MD, of Lausanne University Hospital in Switzerland, pointed out that neoadjuvant studies with chemotherapy have also yielded near pCRs in the 30% range, and pointed to recent U.S. findings with similar results using the same checkpoint combination.
“The real big question is in the end, is neoadjuvant immunotherapy having a positive impact on overall survival?” said Simon, adding that past experience with chemotherapy trials failed to demonstrate that the impressive RFS in responders can lift survival in the overall population. Future will tell whether neoadjuvant immunotherapy will be able to do this.”
Study Details
The phase Ib/II IMCISION trial included 32 head and neck SCC patients with stage II-IVB disease undergoing curative or salvage surgery plus post-operative radiation therapy, 31 of whom were HPV-negative. In all, six participants received either nivolumab alone (240 mg on weeks 1 and 3) and 26 received nivolumab (same dose) plus ipilimumab (1 mg/kg on week 1), with surgery performed at week 5. The phase I portion of the trial included six patients for each treatment option, while the phase II expansion only used the combination.
In the end, three patients did not undergo surgery (one for progressive disease), making 29 evaluable for tumor response, which was assessed by FDG-PET at baseline and prior to surgery.
One patient receiving nivolumab monotherapy and eight of those receiving the combination had a near pCR.
Most patients had stage IVA-B disease (n=11), followed by stage III disease in eight patients and stage II disease in three. Ten patients were undergoing salvage surgery for recurrent disease, six of whom had received prior chemoradiotherapy.
Grade 3/4 immune-related adverse events (AEs) were reported in 12 patients (38%), and included colitis, pericarditis, thyroiditis, lymphopenia, and rash, as well as increased alanine aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase. Toxicities were manageable, said Zuur, and surgery was not delayed in any patient due to immune-related AEs.

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    Ian Ingram joined MedPage Today in 2018 as Deputy Managing Editor, and covers oncology for the site.

Disclosures

The study was funded by Bristol-Myers Squibb (BMS).

Zuur disclosed being a principal investigator (PI) for PI-initiated BMS trials.

Simon disclosed relevant relationships with Merck, Roche, and Pfizer.

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