Neoadjuvant IO Yields Deep Responses in Head and Neck Cancer

Preoperative checkpoint inhibition ended in deep responses in derive sufferers with head and neck squamous cell carcinoma (SCC) with mostly human papillomavirus (HPV)-damaging disease, a puny, single-arm gaze chanced on.

Amongst 29 evaluable sufferers incorporated within the IMCISION trial, 31% finished a reach pathologic complete response (pCR) when handled with two gains 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 Cancer Institute in Amsterdam.

Patients reaching reach pCR, outlined as most predominant tumor shrinkage of as a minimal 90%, had a 14-month recurrence-free survival (RFS) fee of 100%, she talked about on the 2020 European Society for Medical Oncology (ESMO) digital congress.

This survival profit became once critically greater than sufferers with lesser responses within the gaze, which incorporated yet any other 31% of sufferers with responses starting from 20% to 89%, in addition to to a historical cohort of greater than 100 sufferers handled with huge surgery (P<0.05).

“Seventy p.c of head and neck most cancers sufferers video display with evolved-stage disease and need for excessive intensive traditional of care with a somewhat heart-broken total survival,” talked about Zuur, highlighting the need for further effective and much less “mutilating” suggestions.

In some sufferers, responses had been seen on the most predominant voice however no longer within the lymph nodes, whereas in most cases the reverse performed out.

“Whether or no longer these are factual immune responses or a delayed response to immunotherapy that can show with elevated gains of [immune checkpoint blockade] we feature out no longer know at this level of time,” talked about Zuur. She well-known that right here is of scientific importance, as future trials is likely to be designed to gaze de-escalation in sufferers with a reach pCR after neoadjuvant checkpoint blockade.

“The IMCISION regimen of nivolumab with or with out ipilimumab is safe and an efficient neoadjuvant regimen,” Zuur concluded.

Proportion alternate in complete lesion glycolysis on FDG-PET known sufferers with a reach pCR, she talked about.

Translational overview from the trial confirmed that combined certain ranking, tumor mutational burden, and pretreatment hypoxia gene expression didn’t predict response to therapy. On-therapy decreases in hypoxia gene expression, on the opposite hand, and on-therapy increases in endothelial cells had been each correlated with most predominant pathologic responses, and pretreatment COSMIC AID/APOBEC mutational signatures had been enriched in sufferers with reach pCRs.

Researchers also chanced on elevated CD8- and CD3-certain cells in these very fair appropriate responders, despite the indisputable truth that she cautioned that this became once no longer corrected for a pair of testing.

For context, ESMO-invited discussant Christian Simon, MD, of Lausanne College Sanatorium in Switzerland, pointed out that neoadjuvant stories with chemotherapy get also yielded reach pCRs within the 30% fluctuate, and pointed to contemporary U.S. findings with equal results the employ of the identical checkpoint combination.

“The right kind tall ask is within the discontinue, is neoadjuvant immunotherapy having a certain affect on total survival?” talked about Simon, including that past expertise with chemotherapy trials failed to reveal that the spectacular RFS in responders can derive survival within the total inhabitants. Future will expose whether neoadjuvant immunotherapy will be ready to lift out this.”

Survey Notable aspects

The section Ib/II IMCISION trial incorporated 32 head and neck SCC sufferers with stage II-IVB disease present process curative or salvage surgery plus post-operative radiation therapy, 31 of whom had been HPV-damaging. In all, six participants purchased both nivolumab on my own (240 mg on weeks 1 and 3) and 26 purchased nivolumab (identical dose) plus ipilimumab (1 mg/kg on week 1), with surgery performed at week 5. The section I portion of the trial incorporated six sufferers for every therapy chance, whereas the section II expansion most attention-grabbing historical the mix.

In the discontinue, three sufferers didn’t undergo surgery (one for modern disease), making 29 evaluable for tumor response, which became once assessed by FDG-PET at baseline and sooner than surgery.

One affected person receiving nivolumab monotherapy and eight of these receiving the mix had a reach pCR.

Most sufferers had stage IVA-B disease (n=11), adopted by stage III disease in eight sufferers and stage II disease in three. Ten sufferers had been present process salvage surgery for recurrent disease, six of whom had purchased prior chemoradiotherapy.

Grade 3/4 immune-connected adversarial events (AEs) had been reported in 12 sufferers (38%), and incorporated colitis, pericarditis, thyroiditis, lymphopenia, and rash, in addition to to elevated alanine aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase. Toxicities had been manageable, talked about Zuur, and surgery became once no longer delayed in any affected person attributable to immune-connected AEs.