Science

Goutham Sunny: Comparing Two Groundbreaking Neoadjuvant Trials in Locally Advanced HNSCC

Goutham Sunny/X

May 19, 2025, 16:26

Goutham Sunny: Comparing Two Groundbreaking Neoadjuvant Trials in Locally Advanced HNSCC

Goutham Sunny, Resident Doctor at The Gujarat Cancer and Research Institute, shared a post on X:

“Comparing Two Groundbreaking Neoadjuvant Trials in Locally Advanced HNSCC

Study 1: NeoRTPC02 (Liu et al., 2025)

Regimen: Low-dose radiotherapy (LDR) + tislelizumab (PD-1 inhibitor) + nab-paclitaxel + cisplatin.

Design: Phase II, single-arm, multicenter.

Key Findings:

pCR rate: 60.9% (14/23)

MPR rate: 21.7% (5/23)

ORR: 64.3% (18/28)

Safety: Grade 3-4 TRAEs in 35.7% (manageable, no surgical delays).

Biomarkers: ↑CD4/CD8/CD20 post-treatment; higher baseline CD20 linked to pCR.

TME Remodeling: LDR boosted CD8+IL7R+ T cells, reduced immunosuppressive APOE+ macrophages.

Highlights:

LDR synergized with immunotherapy/chemotherapy to achieve one of the highest pCR rates in HNSCC.

HPV status had no significant impact on pCR/MPR.

—

Study 2: NeoCPC (Wu et al., 2024)

Regimen: Camrelizumab (PD-1 inhibitor) + nab-paclitaxel + cisplatin.

Design: Phase II, single-arm.

Key Findings:

pCR rate: 55.6% (15/27)

MPR rate: 63.0% (17/27, combined pCR+MPR)

ORR: 89.6% (43/48)

Safety: Grade 3-4 TRAEs in 6.3% (milder chemo-related toxicity).

Biomarkers: HPV+ patients had better ORR; TP53/TERT mutations correlated with poorer response.

TME: ↑CD8+ T cells and M1-like macrophages linked to response.

Highlights:

Higher ORR but similar pCR vs. NeoRTPC02, likely due to 3 cycles (vs. 2 in NeoRTPC02).

HPV+ tumors showed better radiographic response but no significant pCR difference.

—

Comparative Analysis:

1. Efficacy:

– pCR: Comparable (~55-60%), but NeoRTPC02 included LDR, which may enhance immune activation.

– ORR: NeoCPC higher (89.6% vs. 64.3%), possibly due to extra chemo cycle or regimen differences.

2. Safety:

– NeoCPC had fewer high-grade TRAEs (6.3% vs. 35.7%), but NeoRTPC02’s LDR added no major toxicity.

3. Biomarkers:

– HPV: Minimal impact on pCR in NeoRTPC02 vs. better ORR in HPV+ NeoCPC patients.

– TME: Both studies saw immune infiltration (CD8+ T cells), but NeoRTPC02 uniquely modulated macrophages via LDR.

4. Innovation:

– NeoRTPC02: LDR’s immune priming is a game-changer for chemo-immunotherapy synergy.

–NeoCPC: Durable ORR supports neoadjuvant chemo-immunotherapy alone.

—

Takeaway:

For pCR: LDR combo (NeoRTPC02) may offer superior tumor microenvironment reprogramming.

For safety/tolerability: NeoCPC’s chemo-immunotherapy is less toxic but equally effective.

HPV matters: Not for pCR, but may predict radiographic response.

Future Directions:

Phase III trials needed to validate LDR’s role.

Biomarker-driven strategies (e.g., CD20, TP53) could personalize neoadjuvant therapy.”

Science

OncoDaily

Science

Goutham Sunny: Comparing Two Groundbreaking Neoadjuvant Trials in Locally Advanced HNSCC

“Comparing Two Groundbreaking Neoadjuvant Trials in Locally Advanced HNSCC

Study 1: NeoRTPC02 (Liu et al., 2025)

Regimen: Low-dose radiotherapy (LDR) + tislelizumab (PD-1 inhibitor) + nab-paclitaxel + cisplatin.

Design: Phase II, single-arm, multicenter.

Key Findings:

pCR rate: 60.9% (14/23)

MPR rate: 21.7% (5/23)

ORR: 64.3% (18/28)

Safety: Grade 3-4 TRAEs in 35.7% (manageable, no surgical delays).

Biomarkers: ↑CD4/CD8/CD20 post-treatment; higher baseline CD20 linked to pCR.

TME Remodeling: LDR boosted CD8+IL7R+ T cells, reduced immunosuppressive APOE+ macrophages.

Highlights:

LDR synergized with immunotherapy/chemotherapy to achieve one of the highest pCR rates in HNSCC.

HPV status had no significant impact on pCR/MPR.

—

Study 2: NeoCPC (Wu et al., 2024)

Regimen: Camrelizumab (PD-1 inhibitor) + nab-paclitaxel + cisplatin.

Design: Phase II, single-arm.

Key Findings:

pCR rate: 55.6% (15/27)

MPR rate: 63.0% (17/27, combined pCR+MPR)

ORR: 89.6% (43/48)

Safety: Grade 3-4 TRAEs in 6.3% (milder chemo-related toxicity).

Biomarkers: HPV+ patients had better ORR; TP53/TERT mutations correlated with poorer response.

TME: ↑CD8+ T cells and M1-like macrophages linked to response.

Highlights:

Higher ORR but similar pCR vs. NeoRTPC02, likely due to 3 cycles (vs. 2 in NeoRTPC02).

HPV+ tumors showed better radiographic response but no significant pCR difference.

—

Comparative Analysis:

1. Efficacy:

– pCR: Comparable (~55-60%), but NeoRTPC02 included LDR, which may enhance immune activation.

– ORR: NeoCPC higher (89.6% vs. 64.3%), possibly due to extra chemo cycle or regimen differences.

2. Safety:

– NeoCPC had fewer high-grade TRAEs (6.3% vs. 35.7%), but NeoRTPC02’s LDR added no major toxicity.

3. Biomarkers:

– HPV: Minimal impact on pCR in NeoRTPC02 vs. better ORR in HPV+ NeoCPC patients.

– TME: Both studies saw immune infiltration (CD8+ T cells), but NeoRTPC02 uniquely modulated macrophages via LDR.

4. Innovation:

– NeoRTPC02: LDR’s immune priming is a game-changer for chemo-immunotherapy synergy.

–NeoCPC: Durable ORR supports neoadjuvant chemo-immunotherapy alone.

—

Takeaway:

For pCR: LDR combo (NeoRTPC02) may offer superior tumor microenvironment reprogramming.

For safety/tolerability: NeoCPC’s chemo-immunotherapy is less toxic but equally effective.

HPV matters: Not for pCR, but may predict radiographic response.

Future Directions:

Phase III trials needed to validate LDR’s role.

Biomarker-driven strategies (e.g., CD20, TP53) could personalize neoadjuvant therapy.”