Immuuntherapie naast chemo vooraf aan chemo + radiotherapie bij niet HPV gerelateerde mond- en keelkankermet stadium 3/4 geeft uitstekende resultaten met meer dan 50 procent effectiviteit

24 maart 2025: Bron: JAMA Oncol. Published online March 6, 2025

Wanneer bij patiënten met niet Humaan Papillomavirus - HPV gerelateerde mond- en keelkanker in stadium 3/4 vooraf aan standaardbehandeling van chemo + radiotherapie drie kuren van immuuntherapie worden gegeven naast chemotherapie dan reageert daarop meer dan 50 procent met een gedeeltelijke - of complete remissie. Zo blijkt uit de fase II studie, de DEPEND studie, uitgevoerd door onderzoekers van de Universiteit van Chicago.

De groep patiënten die meer dan 50% tumorkrimp ervoeren, werd toegewezen aan de de-escalatiearm van de studie, terwijl de andere groep standaard chemo-radiotherapie kreeg.
Het hoofddoel van de klinische studie was om de diepe responsratio te evalueren, gedefinieerd als het percentage patiënten dat 50% of meer tumorkrimp bereikte met neoadjuvante chemo-immunotherapie.

De bevindingen waren beter dan verwacht: 53% van de patiënten bereikte een diepe respons met neoadjuvante chemo-immunotherapie. "Dit resultaat overtrof onze verwachtingen ten opzichte van onze historische gegevens met alleen chemotherapie", aldus studieleider dr. Arie Rosenberg.

De beste resultaten werden waargenomen bij patiënten met een hogere expressie van geprogrammeerde dood-ligand 1 (PD-L1), wat suggereert dat PD-L1-expressie kan dienen als een potentiële biomarker om de behandelingsrespons en een potentieel overlevingsvoordeel voor PD-L1-positieve patiënten te voorspellen.

Het volledige studierapport is ondeer bepaalde voorwaarden gratis in te zien of anders te koop en gepubliceerd in JAMA:

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Key Points

Question Is neoadjuvant nivolumab plus chemotherapy followed by response-stratified chemoradiation in nonsurgical locoregionally advanced human papillomavirus (HPV)–negative head and neck squamous cell carcinoma effective and well tolerated?

Findings In this phase 2 nonrandomized clinical trial of 36 patients with stage IVa/b HPV-negative head and neck squamous cell carcinoma, 53% of patients achieved a deep response (≥50% tumor shrinkage per Response Evaluation Criteria in Solid Tumors version 1.1 criteria), which met the statistical end point, while 86% achieved an objective response (≥30% tumor shrinkage per RECIST version 1.1 criteria), with favorable survival. Expression of programmed cell death 1 ligand 1 was a predictive biomarker for response to neoadjuvant chemoimmunotherapy and survival, while de-escalated dose and volume of chemoradiation among deep responders demonstrated lower rates of acute toxic effects.

Meaning In this trial, neoadjuvant nivolumab plus chemotherapy followed by response-stratified chemoradiation in stage IVa/b nonvirally mediated head and neck cancer demonstrated favorable survival and less toxic effects among responders receiving response-adapted chemoradiation.

Abstract

Importance Neoadjuvant immunotherapy in human papillomavirus (HPV)–negative locoregionally advanced (LA) head and neck squamous cell carcinoma (HNSCC) appears promising, yet its role in nonsurgical treatment for head and neck cancer remains undefined. Neoadjuvant nivolumab plus chemotherapy followed by response-stratified de-escalated chemoradiation therapy (CRT) in HPV-negative LA stage IVa/b HNSCC may improve treatment efficacy while reducing treatment-related toxic effects.

Objective To determine the deep response rate and tolerability of neoadjuvant nivolumab plus chemotherapy followed by response-stratified CRT in nonvirally mediated stage IVa/b HNSCC.

Design, Setting, and Participants In this investigator-initiated phase 2 nonrandomized clinical trial conducted at a single academic center, patients with stage IVa/b (American Joint Committee on Cancer Tumor Classification, 8th edition) HPV-negative LA HNSCC were enrolled between 2019 and 2022. Data were analyzed from February 2023 to January 2024.

Interventions The DEPEND trial evaluated neoadjuvant nivolumab plus carboplatin and paclitaxel, followed by response-stratified CRT. Patients with 50% or greater reduction per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 received de-escalated CRT to 66 Gy with elimination of elective nodal volumes; patients with less than 50% reduction received standard CRT to 70 to 75 Gy. Adjuvant nivolumab was administered for 9 cycles.

Main Outcomes and Measures The primary end point was deep response rate (DRR; 50% or greater shrinkage per RECIST version 1.1) following neoadjuvant nivolumab plus chemotherapy. Secondary end points included progression-free survival (PFS), overall survival (OS), locoregional control, and distant control. Exploratory end points included acute toxic effects in patients who received response-adapted de-escalated CRT.

Results Of 36 included patients, 28 (78%) were male, and the median (range) age was 58.9 (27-77) years. All patients started treatment and were available for analysis. The median (range) follow-up was 20 (13-40) months. The primary end point was met, with a DRR following neoadjuvant nivolumab/chemotherapy of 53% (95% CI, 35-70). The objective response rate was 86% (95% CI, 71-95). A total of 19 received de-escalated CRT and 16 received standard CRT. PFS and OS at 2 years were 66% (95% CI, 34-76) and 73% (95% CI, 52-86), respectively. The most common treatment-emergent adverse events for de-escalated and standard CRT were mucositis (14 of 19 [74%] and 15 of 16 [94%], respectively), radiation dermatitis (13 of 19 [68%] and 14 of 16 [88%], respectively), and dry mouth (7 of 19 [37%] and 10 of 16 [63%], respectively).

Conclusions and Relevance In this phase 2 nonrandomized clinical trial, neoadjuvant nivolumab/chemotherapy led to deep responses in 53% of patients with HPV-negative LA stage IVa/b HNSCC, and response-adapted de-escalated CRT led to favorable survival with lower acute toxic effects among deep responders.

Trial Registration ClinicalTrials.gov Identifier: NCT03944915

immuuntherapie, HPV virus, mond- en keelkanker stadium 3/4, chemo + radiotherapie, neoadjuvant, Nivolumab, remissies, JAMA