Preoperative checkpoint inhibition resulted in deep responses in take hang of patients with head and neck squamous cell carcinoma (SCC) with mostly human papillomavirus (HPV)-detrimental illness, a tiny, single-arm glance came across.
Among 29 evaluable patients integrated within the IMCISION trial, 31% achieved a shut to pathologic full response (pCR) when handled with two capabilities of anti-PD-1 nivolumab (Opdivo) with or with out ipilimumab (Yervoy), a CTLA-4-directed immune checkpoint inhibitor, reported Lotje Zuur, MD, PhD, of the Netherlands Most cancers Institute in Amsterdam.
Sufferers reaching shut to pCR, outlined as most essential tumor shrinkage of as a minimal 90%, had a 14-month recurrence-free survival (RFS) rate of 100%, she acknowledged at the 2020 European Society for Medical Oncology (ESMO) digital congress.
This survival support changed into once drastically higher than patients with lesser responses within the glance, which integrated yet any other 31% of patients with responses ranging from 20% to 89%, to boot to a historical cohort of upper than 100 patients handled with huge surgical operation (P<0.05).
“Seventy percent of head and neck most cancers patients most modern with advanced-stage illness and wish for high intensive atypical of care with a fairly wretched overall survival,” acknowledged Zuur, highlighting the necessity for extra efficient and now no more “mutilating” strategies.
In some patients, responses were seen at the key dwelling but now now not within the lymph nodes, whereas in most cases the reverse performed out.
“Whether these are perfect immune responses or a delayed response to immunotherapy that can perhaps perhaps give an explanation for with increased capabilities of [immune checkpoint blockade] we invent now now not know at this level of time,” acknowledged Zuur. She well-liked that here’s of scientific significance, as future trials might perhaps perhaps also merely be designed to glance de-escalation in patients with a shut to pCR after neoadjuvant checkpoint blockade.
“The IMCISION regimen of nivolumab with or with out ipilimumab is stable and an efficient neoadjuvant regimen,” Zuur concluded.
Share trade in complete lesion glycolysis on FDG-PET identified patients with a shut to pCR, she acknowledged.
Translational analysis from the trial confirmed that combined certain rep, tumor mutational burden, and pretreatment hypoxia gene expression did now now not predict response to remedy. On-treatment decreases in hypoxia gene expression, alternatively, and on-treatment will enhance in endothelial cells were each and every correlated with fundamental pathologic responses, and pretreatment COSMIC AID/APOBEC mutational signatures were enriched in patients with shut to pCRs.
Researchers also came across increased CD8- and CD3-certain cells in these soft responders, though she cautioned that this changed into once now now not corrected for a pair of sorting out.
For context, ESMO-invited discussant Christian Simon, MD, of Lausanne College Neatly being facility in Switzerland, pointed out that neoadjuvant studies with chemotherapy indulge in also yielded shut to pCRs within the 30% vary, and pointed to recent U.S. findings with identical outcomes using the identical checkpoint mixture.
“The categorical mountainous query of is within the live, is neoadjuvant immunotherapy having a particular impact on overall survival?” acknowledged Simon, along side that previous ride with chemotherapy trials did now not give an explanation for that the impressive RFS in responders can win survival within the general population. Future will declare whether or now now not neoadjuvant immunotherapy will seemingly be in a diagram to invent this.”
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The phase Ib/II IMCISION trial integrated 32 head and neck SCC patients with stage II-IVB illness undergoing curative or salvage surgical operation plus put up-operative radiation remedy, 31 of whom were HPV-detrimental. In all, six participants bought either nivolumab on my own (240 mg on weeks 1 and 3) and 26 bought nivolumab (identical dose) plus ipilimumab (1 mg/kg on week 1), with surgical operation performed at week 5. The phase I portion of the trial integrated six patients for each and every treatment option, whereas the phase II expansion most attention-grabbing faded the combo.
Within the live, three patients did now now not undergo surgical operation (one for innovative illness), making 29 evaluable for tumor response, which changed into once assessed by FDG-PET at baseline and prior to surgical operation.
One patient receiving nivolumab monotherapy and eight of these receiving the combo had a shut to pCR.
Most patients had stage IVA-B illness (n=11), followed by stage III illness in eight patients and stage II illness in three. Ten patients were undergoing salvage surgical operation for recurrent illness, six of whom had bought prior chemoradiotherapy.
Grade 3/4 immune-connected detrimental events (AEs) were reported in 12 patients (38%), and integrated colitis, pericarditis, thyroiditis, lymphopenia, and rash, to boot to increased alanine aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase. Toxicities were manageable, acknowledged Zuur, and surgical operation changed into once now now not delayed in any patient attributable to immune-connected AEs.
Ian Ingram joined MedPage This day in 2018 as Deputy Managing Editor, and covers oncology for the dwelling.
The glance changed into once funded by Bristol-Myers Squibb (BMS).
Zuur disclosed being a predominant investigator (PI) for PI-initiated BMS trials.
Simon disclosed relevant relationships with Merck, Roche, and Pfizer.