Buparlisib and Chemotherapy Combination Lacks Overall Survival Benefit in PD-1-Treated Recurrent Head and Neck Cancer

buparlisib Combination Fails to Improve Survival in Recurrent Head and Neck Cancer

Berlin, Germany – New Data Presented at the 2025 ESMO congress has revealed that a combination therapy of buparlisib and paclitaxel did not demonstrate a statistically important enhancement in overall survival compared to paclitaxel alone in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) whose disease had progressed after treatment with PD-1 or PD-L1 inhibitors. The results of the Phase 3 BURAN trial (NCT04338399) were unveiled during the prestigious medical conference.

Key Findings From the BURAN Trial

The study, which involved 487 patients, showed a median overall survival of 9.6 months for those receiving the buparlisib and paclitaxel combination, compared to 9.7 months for patients treated with paclitaxel alone. The hazard ratio was 1.02, with a 95% confidence interval of 0.83-1.26 (P = .85),indicating no significant difference between the two treatment arms.

Lead Study Author, Denis Souliéres, MD, msc, FRCPC, Full Professor of Medicine at the Université de Montréal in Canada, stated during his presentation that while the combination therapy exhibited a numerically higher overall response rate, it did not translate into improved progression-free survival. Dr. Souliéres emphasized the need for further translational research to identify potential molecular subgroups that may benefit from this approach.

Buparlisib, an oral pan-PI3K inhibitor, has shown promise in earlier studies, including Phase 1b data demonstrating clinical activity in taxane-pretreated advanced solid tumors. The Phase 2 BERIL-1 trial had previously suggested a progression-free survival and overall survival improvement with the buparlisib and paclitaxel combination, but these findings have not been replicated in the larger Phase 3 BURAN trial.

Patient Population and Study Design

Patients enrolled in the BURAN trial had recurrent or metastatic HNSCC and had previously received a PD-1/PD-L1 inhibitor. they also had received one to two prior lines of therapy and had an ECOG performance status of 0 or 1. Participants were randomly assigned in a 2:1 ratio to receive either buparlisib (100 mg once daily) plus paclitaxel (80 mg/m² every three weeks) or paclitaxel alone.

Characteristic	Buparlisib + Paclitaxel (n=325)	Paclitaxel Alone (n=162)
Median Overall Survival (Months)	9.6	9.7
Hazard Ratio (HR)	1.02	–
95% Confidence Interval	0.83-1.26	–
HPV Positive (%)	29.8	29.8

Did You Know? Head and neck squamous cell carcinoma accounts for approximately 85% of all head and neck cancers, with an estimated 54,069 new cases in the United States in 2024, according to the American Cancer society.

Safety and Adverse Events

The combination of buparlisib and paclitaxel was associated with a higher incidence of grade 3 or higher adverse events (87.5%) compared to paclitaxel alone (59.4%). Treatment-related grade 3 or higher AEs were reported in 71.0% of patients receiving the combination therapy and 33.8% of those receiving monotherapy. Most discontinuations in the combination arm were due to disease progression or adverse events.

Pro Tip: Patients experiencing adverse effects from cancer treatment should communicate openly with their healthcare team to manage symptoms and ensure the best possible quality of life.

Subgroup Analysis and Future Directions

Analysis revealed a potential survival advantage in patients with HPV-positive oropharynx cancer, although this finding was not statistically significant overall. Additionally,North American patients exhibited a statistically significant survival advantage with the combination therapy compared to Asian Pacific and European patients. Researchers are planning further investigations to explore these discrepancies and identify biomarkers that could predict response to treatment.

Understanding HNSCC and Treatment Landscape

Head and neck squamous cell carcinoma (HNSCC) is a complex disease with a challenging prognosis. Current treatment options include surgery,radiation therapy,chemotherapy,and immunotherapy. While immunotherapy has shown significant benefits for some patients, a ample proportion do not respond or develop resistance.The BURAN trial highlights the ongoing need for new therapeutic strategies to improve outcomes for individuals with recurrent or metastatic HNSCC.

The PI3K pathway is frequently dysregulated in HNSCC, making it an attractive target for therapeutic intervention. Buparlisib’s ability to inhibit all four isoforms of class I PI3K had initially generated optimism, but the BURAN trial results suggest that broader PI3K inhibition may not be sufficient to overcome resistance mechanisms or achieve significant clinical benefit in this patient population.

Frequently Asked Questions about Buparlisib and HNSCC

Do you think further research into biomarkers could help personalize treatment for HNSCC patients? Share your thoughts in the comments below!

Stay informed about the latest developments in cancer research. Subscribe to Archyde news for updates.

What are the implications of the study findings for treatment sequencing in patients with recurrent HNSCC after PD-1 inhibitor failure?

Understanding the Study Findings

Recent research has indicated that adding buparlisib to standard chemotherapy regimens dose not improve overall survival (OS) in patients with recurrent head and neck squamous cell carcinoma (HNSCC) who have previously received PD-1 inhibitor therapy.This is a important finding,impacting treatment strategies for this challenging patient population. The study, presented at a major oncology conference and afterward published, investigated the efficacy of this combination as a second-line treatment option. Recurrent HNSCC, particularly after PD-1 blockade failure, presents a considerable clinical challenge.

buparlisib: A PI3K Inhibitor & Its Role in HNSCC

Buparlisib is a phosphatidylinositol 3-kinase (PI3K) inhibitor. The PI3K/AKT/mTOR pathway is frequently dysregulated in HNSCC, making it an attractive therapeutic target. preclinical studies suggested that inhibiting this pathway could enhance the effectiveness of chemotherapy. The rationale behind combining buparlisib with chemotherapy was to overcome resistance mechanisms and improve treatment outcomes. PI3K inhibitors are a class of drugs gaining attention in cancer treatment.

Why the Combination Was Investigated

* PD-1 Resistance: A significant proportion of patients with recurrent HNSCC develop resistance to PD-1 inhibitors (like pembrolizumab or nivolumab).

* PI3K Pathway Activation: Alterations in the PI3K pathway are common in HNSCC and can contribute to resistance to both chemotherapy and immunotherapy.

* Synergistic Potential: researchers hypothesized that buparlisib could synergize with chemotherapy, perhaps restoring sensitivity and improving survival.

key Results of the Clinical Trial

The clinical trial involved patients with locally advanced or metastatic HNSCC who had progressed after prior treatment with a PD-1 inhibitor. Patients were randomized to receive either:

1. Standard chemotherapy (typically platinum-based) plus buparlisib.
2. Standard chemotherapy alone.

The primary endpoint was overall survival. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety.

* Overall Survival (OS): the study demonstrated no statistically significant difference in overall survival between the two groups. This was the most critical finding.

* Progression-Free Survival (PFS): While there was a trend towards improved PFS with the buparlisib combination, it did not reach statistical significance.

* objective Response Rate (ORR): The ORR was similar in both arms of the study.

* Safety Profile: Buparlisib is associated with a notable side effect profile,including hyperglycemia,rash,and colitis. The combination arm experienced a higher incidence of these adverse events. Chemotherapy side effects were also observed, as was to be expected.

Implications for Clinical Practise

These findings have critically important implications for the management of recurrent HNSCC. The addition of buparlisib to chemotherapy should not be considered a standard treatment option for patients who have progressed after PD-1 inhibitor therapy.

* Treatment Sequencing: Clinicians should carefully consider choice treatment strategies, such as clinical trials evaluating novel agents or different immunotherapy approaches.

* Biomarker Research: Further research is needed to identify biomarkers that may predict which patients are most likely to benefit from PI3K inhibition. Identifying patients with specific PI3K mutations might be crucial.

* Focus on Alternative Therapies: Exploring other targeted therapies and immunotherapeutic combinations remains a priority.

Real-World Considerations & Patient Management

In clinical practice, the decision to use buparlisib (or any second-line therapy) must be individualized, taking into account the patient’s performance status, comorbidities, and treatment preferences. A thorough discussion of the potential benefits and risks is essential.

Managing Patient Expectations

It’s crucial to manage patient expectations regarding treatment options after PD-1 inhibitor failure. The lack of significant benefit with buparlisib highlights the need for realistic discussions about prognosis and the importance of palliative care. palliative care for head and neck cancer focuses on symptom management and improving quality of life.

Future Research directions

Ongoing research is focused on:

* Identifying Predictive Biomarkers: Researchers are actively searching