At the ESMO Congress 2026 in Madrid, Spain, Marc Oliva presented the final results of the phase II RADIAN trial (TTCC-2022-01), evaluating the combination of niraparib, dostarlimab and radiotherapy in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC).
Presented as Late-Breaking Abstract LBA46, the study investigated whether incorporating the PARP inhibitor niraparib and the PD-1 inhibitor dostarlimab into definitive treatment could improve clinical outcomes in patients eligible for cisplatin-based chemoradiotherapy (CRT) and those considered unfit for cisplatin.
The findings demonstrated contrasting outcomes between the two treatment cohorts. Among patients receiving cisplatin-based chemoradiotherapy, the study met its primary endpoint, achieving a 1-year disease-free survival (DFS) rate of 88.2%, compared with a historical benchmark of 65% (HR 0.19; p=0.01). However, in patients receiving radiotherapy without cisplatin, the addition of niraparib was associated with increased and prolonged toxicity, including two treatment-related deaths, without a significant DFS benefit.
RADIAN Trial: Evaluating PARP Inhibition and Immunotherapy Alongside Radiotherapy
The RADIAN trial investigated the clinical activity and safety of niraparib and dostarlimab administered alongside definitive chemoradiotherapy or radiotherapy alone in patients with stage III–IVB head and neck squamous cell carcinoma.
Eligible patients had PD-L1 combined positive score (CPS) greater than 1 and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1.
The study included two cohorts:
- Cohort A: Patients eligible for standard cisplatin-based chemoradiotherapy.
- Cohort B: Patients considered unfit for cisplatin and treated with radiotherapy alone.
Patients received an initial intravenous dose of dostarlimab 500 mg three weeks before radiotherapy, followed by niraparib 200–300 mg daily beginning two weeks before radiotherapy.
In cohort A, niraparib was administered until the start of chemoradiotherapy, while in cohort B, niraparib continued throughout radiotherapy.
Maintenance treatment with dostarlimab 500 mg every three weeks plus niraparib began four weeks after radiotherapy and continued for up to 14 cycles.
The primary endpoint was 1-year disease-free survival, evaluated against historical outcomes, with an expected hazard ratio below 0.64 and a one-sided significance threshold of 0.10. Secondary objectives included safety and additional efficacy measures, while post-radiotherapy overall response was assessed using RECIST 1.1 criteria.
The planned enrollment was 34 patients, with 17 patients included in each cohort. The data cutoff was September 1, 2026.
Cohort A: Improved Disease-Free Survival With Cisplatin-Based Chemoradiotherapy
In cohort A, which included 17 patients eligible for standard chemoradiotherapy, the addition of niraparib and dostarlimab was associated with encouraging disease-control outcomes.
The median age was 65 years (range, 41–68), and 71% of patients were male. The primary tumor sites included the larynx (53%), oropharynx (41%) and hypopharynx (6%).
All 17 patients received the planned pre-radiotherapy doses of dostarlimab and niraparib, while 15 patients (88%) completed radiotherapy at 70 Gy.
Among the 15 patients evaluable for response, the overall response rate (ORR) was 93%, comprising 13 complete responses and one partial response.
The primary endpoint was met:
- 1-year DFS: 88.2% (95% CI, 74.2–100).
- Historical 1-year DFS: 65%.
- Hazard ratio: 0.19.
- P-value: 0.01.
At a median follow-up of 17 months (95% CI, 16–25), all 15 surviving patients remained alive without recurrence.
Despite the favorable efficacy findings, treatment-related toxicity remained an important concern. Two patients died during chemoradiotherapy due to adverse events, including one death considered related to niraparib.
Maintenance therapy was initiated in 14 patients (82%), and eight patients (47%) completed treatment. Seven patients (41%) discontinued dostarlimab and/or niraparib because of treatment-related adverse events.
Niraparib dose reductions and interruptions were reported in 65% and 71% of patients, respectively.
These findings indicate that the regimen achieved the predefined efficacy endpoint in the cisplatin-eligible population, although its safety profile requires careful consideration.
Cohort B: Increased Toxicity Without Significant Survival Benefit
In contrast, the results from cohort B raised substantial safety concerns regarding the combination of niraparib, dostarlimab and radiotherapy in patients unable to receive cisplatin.
This cohort included 17 patients, with a median age of 73 years (range, 68–75). Most patients were male (94%), and nearly half (47%) had stage IVB disease.
All patients completed the prescribed 70 Gy radiotherapy course, while 16 patients (94%) completed pre-radiotherapy niraparib.
The overall response rate among 15 evaluable patients was 100%, including 11 complete responses and four partial responses.
However, these initial responses did not translate into a statistically significant improvement in disease-free survival.
The 1-year DFS rate was 61% (95% CI, 40–91), compared with a historical rate of 55% (HR 0.72; p=0.19).
Four patients experienced disease recurrence. At a median follow-up of 13.6 months (95% CI, 7.8–16.4), 10 of the 12 surviving patients remained recurrence-free.
Importantly, all patients experienced grade 3 or higher treatment-related adverse events. Niraparib-related and dostarlimab-related adverse events were reported in 76% and 29% of patients, respectively.
Mucositis and odynodysphagia were the most common adverse events leading to treatment interruption or discontinuation.
Five deaths were reported in this cohort: two related to niraparib and radiotherapy, one associated with an unrelated adverse event, and two due to disease progression.
Maintenance therapy was initiated in 13 patients (76%), but only one patient (6%) completed the planned course. Ten patients (59%) discontinued dostarlimab and/or niraparib because of treatment-related adverse events.
The investigators concluded that niraparib increased and prolonged radiotherapy-associated toxicity in cisplatin-ineligible patients without providing a meaningful DFS improvement.
What Do the RADIAN Findings Mean for Clinical Practice?
The final RADIAN results highlight an important difference in the clinical outcomes of combining PARP inhibition and immune checkpoint blockade with definitive treatment according to cisplatin eligibility.
In patients eligible for cisplatin-based chemoradiotherapy, the investigational regimen met its primary endpoint, with a 1-year DFS rate of 88.2% and no recurrences reported among the 15 surviving patients at the median follow-up of 17 months.
However, these results were obtained in a small, non-randomized study using historical comparisons rather than a concurrent control group. Consequently, the observed improvement in DFS cannot be attributed definitively to the investigational agents without further controlled evaluation.
The findings in cisplatin-ineligible patients were less favorable. Although the initial response rate reached 100% among evaluable patients, the absence of a statistically significant DFS benefit, together with severe and prolonged toxicity, limits the clinical applicability of this approach.
The occurrence of treatment-related deaths in both cohorts further emphasizes the need to balance potential improvements in disease control against treatment tolerability.
Conclusion: Promising Efficacy, but Safety Remains a Major Consideration
The final analysis of the RADIAN trial presented at ESMO Congress 2026 demonstrated that niraparib and dostarlimab combined with cisplatin-based chemoradiotherapy met the predefined 1-year DFS endpoint in patients with locally advanced head and neck squamous cell carcinoma.
However, the combination of niraparib and dostarlimab with radiotherapy alone did not demonstrate a significant DFS benefit and was associated with substantial toxicity, including two deaths related to niraparib and radiotherapy.
The RADIAN findings support further investigation of this treatment strategy in cisplatin-eligible patients while raising important safety concerns regarding its use in patients unable to receive cisplatin. Larger controlled studies will be necessary to establish its efficacy, safety and potential role in clinical practice.
Study information
- Abstract: LBA46 – Niraparib and dostarlimab plus radiotherapy (RT) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC) patients (TTCC-2022-01 RADIAN).
- Presenter: Marc Oliva (Madrid, Spain).
- Study group: TTCC Grupo Español de Tratamiento de Tumores de Cabeza y Cuello.
- Clinical trial registration: NCT05784012; Eu-CT 2024-516779-33-00.
- Funding: GSK.
- Data cutoff: September 1, 2026.
- Source: ESMO Congress 2026 – LBA46 Abstract.
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