Perioperative Immunotherapy in Head and Neck Cancer: Camrelizumab and Pembrolizumab
In this article
Perioperative Immunotherapy in Head and Neck Cancer: Camrelizumab and Pembrolizumab
In the CAMORAL phase 2 trial, published in JAMA Oncology on 12 November 2026, patients who received camrelizumab plus chemotherapy before surgery and camrelizumab after surgery were compared with the standard "surgery first" approach: 2-year event-free survival was 77.8% versus 46.1% among 125 patients (HR 0.34; 95% CI 0.17-0.68). This is a strong signal. But it is a small phase 2 trial, most patients had oral cavity cancer, and grade 3 or higher adverse events were 79.4% in the experimental arm and 56.5% in the control arm. Moreover, no direct comparison was made with the current perioperative pembrolizumab strategy. In this article we place the two approaches side by side; we do not lay their results over one another. We also covered pembrolizumab in our pembrolizumab article (in Turkish).
- What was found? In resectable stage III-IVB head and neck squamous cell carcinoma, 2 cycles of chemotherapy plus camrelizumab before surgery and camrelizumab after surgery raised 2-year event-free survival from 46.1% to 77.8% (HR 0.34; p=0.001). Major pathological response was 47.6% and complete pathological response 25.4%; both were 0% in the control arm.
- Relationship to pembrolizumab: Perioperative pembrolizumab (KEYNOTE-689) received FDA approval on 12 June 2025 for resectable locally advanced disease with PD-L1 CPS 1 or higher. These two approaches were not compared in the same trial.
- How to read it? A small, open-label, 4-center (China) phase 2 trial; there is pharmaceutical company support; follow-up is 24.6 months. The result is a strong rationale for phase 3, but on its own it does not change the standard.
- What it is not: It does not mean "camrelizumab is superior to pembrolizumab" or "chemotherapy should be added"; the trial has no PD-1-alone arm, so the added contribution of chemotherapy cannot be separated.
Why does this topic matter?
In resectable locally advanced head and neck squamous cell carcinoma, treatment is usually built on surgery followed by risk-adapted radiotherapy (with cisplatin when needed). Even so, recurrence and distant metastasis are common. Extending immunotherapy to both before and after surgery is tried in the hope of starting the immune response while the tumor is still in place and reducing recurrence.
There is now a reference point in this field: in the KEYNOTE-689 trial, adding pembrolizumab for 2 cycles before surgery and 15 cycles after surgery improved event-free survival in 714 patients and led to approval in the United States for patients with PD-L1 CPS 1 or higher. CAMORAL, by contrast, is a smaller trial from China testing a different strategy: chemotherapy was also added to the treatment before surgery.
The key point separating the two is this: in KEYNOTE-689 the treatment before surgery was pembrolizumab alone; in CAMORAL, camrelizumab was given together with chemotherapy. So the numbers of the two trials cannot be read as two answers to the same question.
How was CAMORAL conducted?
Patients were assigned 1:1 to the experimental or control arm. In the experimental arm, 2 cycles of chemotherapy plus camrelizumab were given before surgery, followed after surgery by radiotherapy and camrelizumab maintenance; in the control arm, surgery was done first.
Figure 1 · Flow of the experimental arm
Sequence of perioperative treatment in CAMORAL
Study design and patients
| Feature | Reported | Why it matters |
|---|---|---|
| Study type | CAMORAL (ChiCTR2000037980): multicenter, open-label, randomized phase 2; 4 university hospitals in China. Enrollment October 2020 to March 2024; data cutoff 11 April 2025 | Phase 2 and a small sample; results are not definitive evidence, but a rationale for phase 3 |
| Patients | 125 patients (63 experimental, 62 control); aged 18-75, untreated, resectable stage III-IVB head and neck squamous cell carcinoma (nasopharynx excluded), ECOG 0-1. Primary tumor in the oral cavity: 82.4%. Stage IV: 77.8% and 75.8%. HPV positive: 4.8% and 3.2% | Oral cavity predominant; results may not apply directly to oropharynx or larynx |
| Experimental arm | 2 cycles (21 days) before surgery of nab-paclitaxel + carboplatin (AUC 5; or cisplatin 75 mg/m²) + camrelizumab 200 mg; surgery 3-6 weeks later; radiotherapy after surgery (may be omitted with complete pathological response; with cisplatin for extranodal extension or positive surgical margin); up to 15 cycles of adjuvant camrelizumab | A chemotherapy + PD-1 combination; the contribution of PD-1 alone cannot be separated |
| Control arm | Surgery first; then risk-adapted adjuvant radiotherapy, with cisplatin for extranodal extension or positive margin | There is no control group receiving chemotherapy before surgery |
| PD-L1 distribution | CPS 20 or higher: 38.1% (experimental), 27.4% (control); CPS below 1: 11.1% and 14.5% | PD-L1 was not a stratification factor; high CPS was more common in the experimental arm |
| Primary endpoint | 2-year event-free survival (from randomization; progression precluding surgery, recurrence or metastasis, second primary cancer, or loss of life) | The event definition also includes second primary cancer |
| Follow-up | Median 24.6 months (interquartile range 16.8-36.5) | Short follow-up; long-term results are uncertain |
The table is compiled from the JAMA Oncology article. The study was conducted with drug and technical support from the pharmaceutical company Jiangsu Hengrui; the company also had a role in design, data and analysis.
What do the results say?
| Measure | Experimental (n=63) | Control (n=62) | Note |
|---|---|---|---|
| 2-year event-free survival | 77.8% (95% CI 63.6-87.0) | 46.1% (31.3-59.6) | Primary endpoint; HR 0.34 (0.17-0.68), p=0.001 |
| Median event-free survival | Not reached | 21.5 months (8.6-not estimable) | Events: 13 (20.6%) and 29 (46.8%) |
| Major pathological response | 47.6% (30/63) | 0% | Nominal p<0.001 |
| Complete pathological response | 25.4% (16/63) | 0% | Nominal p<0.001 |
| 2-year overall survival | 92.0% (81.8-96.6) | 69.1% (54.5-79.8) | HR 0.25 (0.10-0.64); nominal p=0.002; secondary endpoint |
| 2-year distant metastasis-free survival | HR 0.15 (0.03-0.68) | Nominal p=0.005 | |
| 2-year locoregional recurrence-free survival | HR 0.61 (0.28-1.30) | p=0.20; not significant | |
| Completion of surgery | 58/63 (92.1%) | 57/62 (91.9%) | Surgery was delayed in 10/58 (17.2%) patients in the experimental arm; mostly COVID-19-related (7 patients) |
None of the 13 events in the experimental arm was a loss of life or a second primary cancer; in the control arm, 13 of the events were locoregional, 10 distant metastasis, 2 loss of life and 4 second primary cancer. Subgroup results are exploratory.
Figure 2 · 2-year survival in CAMORAL
Event-free and overall survival rates (%); 63 patients in the experimental arm, 62 in the control arm. The bars compare only these two measures.
Safety: what is the cost?
| Event | Experimental (n=63) | Control (n=62) |
|---|---|---|
| Grade 3 or higher adverse event | 50 (79.4%) | 35 (56.5%) |
| Grade 3 or higher serious adverse event | 13 (20.6%) | 10 (16.1%) |
| Grade 3 or higher lymphopenia | 29 (46.0%) | 14 (22.6%) |
| Grade 3 or higher neutropenia | 17 (27.0%) | Not separately reported |
| Grade 3 or higher oral mucositis | 15 (23.8%) | 16 (25.8%) |
| Treatment-related loss of life | 0 | 1 (1.6%) |
In the experimental arm, reactive cutaneous capillary endothelial proliferation (a skin finding specific to camrelizumab) was seen in 90.5%; all were grade 1 or 2. Because of adverse events, camrelizumab was permanently discontinued in 11 patients (17.5%). These figures are "treatment-emergent" events.
CAMORAL and KEYNOTE-689 side by side
The two trials tested perioperative PD-1 blockade in the same disease group. But their designs, patients and treatments differ. The table below shows these differences; the result rows should not be substituted for one another.
| Feature | CAMORAL (camrelizumab) | KEYNOTE-689 (pembrolizumab) |
|---|---|---|
| Stage and size | Phase 2, 125 patients; stage III-IVB; China, 4 centers | Phase 3, 714 patients; stage III-IVA; multicenter |
| Patients | 82.4% oral cavity | Stage III-IVA head and neck squamous cell carcinoma; site distribution not detailed in this article |
| Before surgery | 2 cycles of nab-paclitaxel + platinum + camrelizumab | 2 cycles of pembrolizumab, without chemotherapy |
| After surgery | Radiotherapy (± cisplatin) + up to 15 cycles of camrelizumab | Pembrolizumab together with radiotherapy (± cisplatin), then alone; 15 cycles in total |
| Control | Surgery first, risk-adapted adjuvant radiotherapy | Surgery first, adjuvant radiotherapy (± cisplatin) |
| PD-L1 requirement | None (patients with CPS below 1 included) | All patients included; FDA approval is for CPS 1 or higher |
| Event-free survival | 77.8% / 46.1% at year 2; HR 0.34 | In all patients median 51.8 / 30.4 months; HR 0.73 (0.58-0.92). In CPS 1 or higher 59.7 / 29.6 months; HR 0.70 (0.55-0.89) |
| Major pathological response | 47.6% / 0% | 9.4% / 0% (all patients) |
| Grade 3 or higher adverse event | 79.4% / 56.5% (treatment-emergent) | 44.6% / 42.9% (treatment-related) |
| Status | Phase 2; phase 3 needed | FDA-approved (12 June 2025, CPS 1 or higher) |
The pembrolizumab data are from press and ASCO Post sources reporting the first interim analysis (data cutoff 24 July 2024). In each row the first value is the experimental arm, the second the control arm.
Why can they not be compared directly?
- Different treatments: In CAMORAL, chemotherapy + PD-1; in KEYNOTE-689, PD-1 alone. CAMORAL has no PD-1-alone arm; the added contribution of chemotherapy is unknown. The authors also state this openly.
- Different patients: In CAMORAL, 82.4% of patients had oral cavity cancer, and the sample is small. KEYNOTE-689 covers a much larger group of patients (714 patients).
- Different course of the control arm: In the CAMORAL control arm, 2-year event-free survival is 46.1%; in KEYNOTE-689, in all patients, the control arm is 54.6% at month 24. This difference between control groups shows why the experimental-arm numbers cannot be read as equal to each other.
- Different follow-up and drug: In CAMORAL median follow-up is 24.6 months; in KEYNOTE-689, 38.3 months. The drugs are also different (camrelizumab and pembrolizumab).
- Different adverse event definitions: CAMORAL reports treatment-emergent events, the KEYNOTE-689 sources report treatment-related events.
What does it mean, and what does it not mean?
- Small phase 2 trial: 125 patients, 4 centers, one country. Subgroup interpretation and generalizability are limited.
- Short follow-up: Median 24.6 months. Secondary results such as overall survival are at nominal significance and may change in the long term.
- Open-label design and company role: The pharmaceutical company provided drug and technical support and also had a role in design and analysis.
- PD-L1 imbalance: Patients with CPS 20 or higher were more common in the experimental arm and CPS was not a stratification factor. Biomarker analysis is limited to PD-L1; tumor mutational burden was not examined.
- No PD-1-alone arm: The added contribution and added toxicity of chemotherapy cannot be separated.
- High toxicity: Grade 3 or higher adverse events were 79.4% in the experimental arm and 56.5% in the control arm; lymphopenia and neutropenia stand out.
- This result does not change treatment for now: CAMORAL is phase 2. The availability of camrelizumab for this indication in Türkiye has not been verified in this article.
- Pembrolizumab: It was approved in the United States for this indication on 12 June 2025. Its licensing and reimbursement status in Türkiye may change; ask your treatment team (access in Türkiye to FDA-approved drugs, SGK reimbursement conditions; both in Turkish).
- Tumor board: The decision on treatment before surgery is made by evaluating together the ENT/head and neck surgeon, medical oncologist and radiation oncologist.
- PD-L1 testing: Pembrolizumab approval depends on the CPS value; you can ask your doctor about the PD-L1 CPS result of your tumor.
- Clinical trials: You can talk to your doctor about taking part in perioperative immunotherapy trials (what is a clinical trial?, in Turkish).
Questions you can ask your doctor
- Is my disease suitable for treatment before surgery, and is immunotherapy recommended before or after surgery?
- What is my PD-L1 CPS value and does it affect the pembrolizumab option?
- What is known about the added benefit and side effects of adding chemotherapy before surgery?
- Is there a clinical trial I could join?
Common misconceptions
- "CAMORAL left pembrolizumab behind." No. The two strategies were not compared directly; the patients, treatments and control groups differ (how to read research results correctly, in Turkish).
- "Adding chemotherapy always gives a better result." No. CAMORAL has no PD-1-alone arm; the added benefit is unknown and adverse events are more frequent.
- "If a phase 2 gives an HR of 0.34, this is now the standard." No. Small phase 2 results often shrink in phase 3 (common misconceptions about cancer, in Turkish).
Frequently Asked Questions
- What was found in the CAMORAL trial?
- In resectable stage III-IVB head and neck cancer, perioperative camrelizumab plus chemotherapy gave 2-year event-free survival of 77.8%, versus 46.1% in the control arm (HR 0.34). Grade 3 or higher adverse events were 79.4% versus 56.5%.
- Are the CAMORAL results better than pembrolizumab?
- Unknown. The two trials were not compared directly; the patients, treatment regimens and follow-up times differ. Looking at them side by side does not show that one is superior to the other.
- What does immunotherapy before surgery mean?
- It is immunotherapy given before surgery, while the tumor is in place. The aim is to start the immune response early and reduce recurrence; together with treatment after surgery it is called "perioperative" treatment.
- What can patients expect from this result?
- No change in treatment should be expected in the short term. The value of the camrelizumab + chemotherapy strategy will become clear with larger phase 3 trials.
Glossary
- Perioperative treatment
- A treatment plan given both before and after surgery.
- Neoadjuvant treatment
- Treatment given before surgery.
- Event-free survival (EFS)
- The time or proportion for which certain events (progression precluding surgery, recurrence, metastasis, second cancer or loss of life) have not occurred after treatment.
- Major pathological response (MPR)
- Very few viable tumor cells (in most definitions 10% or less) remaining in the surgical specimen.
- Complete pathological response (pCR)
- No viable tumor cells remaining in the surgical specimen.
- PD-1 inhibitor
- A drug that eases the PD-1 brake on immune cells; camrelizumab and pembrolizumab belong to this group.
- PD-L1 CPS
- The combined positive score of cells carrying PD-L1 in a tumor sample; pembrolizumab approval is for patients with CPS 1 or higher.
- Hazard ratio (HR)
- A measure comparing the rate at which an event occurs between two groups. Below 1 shows the event is less frequent in the experimental arm.
- Phase 2 trial
- A relatively small research stage in which first signs of a treatment's effect are sought.
- Phase 3 trial
- The pre-approval stage in which a new treatment is compared with standard treatment in large groups of patients.
DROZDOGAN Academy Commentary
A randomized phase 2 trial that gives a benefit signal for adding chemotherapy to a perioperative PD-1 strategy, but must be read carefully because of its toxicity and the lack of a direct comparison.
⚡ Why it matters
Perioperative immunotherapy is forming a new standard area in resectable head and neck cancer. CAMORAL is among the first randomized data asking about the place of chemotherapy in this area.
✅ Strengths
Randomized design; a marked difference in event-free survival and pathological response; surgery could largely be done on time; a signal in the same direction for overall survival and distant metastasis.
⚠️ Limits
Phase 2 and 125 patients; open-label; oral cavity predominant; 24.6 months of follow-up; PD-L1 imbalance; no PD-1-alone arm; high grade 3 or higher toxicity; company support.
🩺 In practice
The decision is made in the tumor board, based on approved options with strong evidence (including pembrolizumab according to PD-L1 status). We describe CAMORAL as a research signal and do not present it to patients as a standard treatment recommendation.
❓ Open questions
Does chemotherapy add benefit over giving PD-1 alone? Which patients truly need this intensity? What is the result in PD-L1-negative patients? How will long-term survival and toxicity evolve?
Conclusion: CAMORAL is a strong phase 2 signal for perioperative chemo-immunotherapy. It can be read alongside pembrolizumab, but it is not a comparison; the answer to the question should be sought in phase 3 trials.
- This article was prepared in November 2026.
- The CAMORAL figures were taken from the full text of the JAMA Oncology article. The figures on KEYNOTE-689 and the pembrolizumab approval were taken from ASCO Post and OncLive reports; the original publication (NEJM) was not examined directly in this article. Because the sources contain different subgroup figures (all patients, CPS 1 or higher, CPS 10 or higher), the table states which one was used.
- The two trials were not compared directly; the table only places the design differences and the reported results side by side. The diagrams are simplified. The Academy commentary is ours.
- This article is not medical advice; make decisions about your health together with your doctor.
Sources
- Liu F, Zhang Y, Ma H, et al. Perioperative Camrelizumab Plus Chemotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Randomized Clinical Trial. JAMA Oncol. Online 12 November 2026. doi:10.1001/jamaoncol.2026.4642. jamanetwork.com
- The ASCO Post. FDA Approves Neoadjuvant and Adjuvant Pembrolizumab for Resectable Locally Advanced Head and Neck Cancer. June 2025. ascopost.com
- OncLive. Perioperative Pembrolizumab Poses a New Standard of Care Option in Resectable Locally Advanced HNSCC. 27 April 2025. onclive.com
- The ASCO Post. Addition of Neoadjuvant/Adjuvant Pembrolizumab Significantly Improves Outcomes in Locally Advanced HNSCC. April 2025. ascopost.com
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