PD-1抗体再显效－纳武利尤单抗治疗皮肤鳞状细胞癌效果好

The 2022 American Society of Clinical Oncology (ASCO) Annual Meeting was held in Chicago from June 3 to 7. During the meeting, researchers reported the latest research progress in the treatment of skin cell cancer. Also a PD-1 antibody, nivolumab has been confirmed to show good efficacy and safety in the treatment of cutaneous squamous cell carcinoma after cimepilimab.

Disease introduction

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, second only to basal cell carcinoma. It usually occurs on the head and face, followed by the upper and lower limbs, and usually manifests as nodules or ulcers.

In addition, the incidence of cutaneous squamous cell carcinoma increases with age, and is more common in middle-aged and elderly people.

Research background and significance

Previously, the PD-1 antibody cemiplimab (Libtayo) was officially approved by the FDA in September 2018 for the treatment of patients with metastatic cutaneous squamous cell carcinoma or locally advanced unresectable cutaneous squamous cell carcinoma. Clinical trial data show that nearly half of patients (47.2%) responded to cimepilimab treatment.

Programmed death receptor-1 (PD-1) antibodies have shown good therapeutic effects in cutaneous squamous cell carcinoma and have now become a new standard treatment for advanced cutaneous squamous cell carcinoma. Clinical studies of other PD-1 antibodies in cutaneous squamous cell carcinoma are also ongoing.

The study presented here evaluates the efficacy and safety of another PD-1 antibody, nivolumab, in patients with locally advanced or metastatic cutaneous squamous cell carcinoma, including a highly susceptible subgroup with concomitant hematologic malignancies (CHM).

experimental design

The NIVOSQUACS trial (NCT04204837) was a phase II, open-label, single-arm, multicenter study enrolling patients ≥18 years of age with histologically confirmed locally advanced and/or metastatic cutaneous squamous cell carcinoma and at least one measurable lesion according to RECISTv1.1 criteria.

Between July 2017 and October 2020, a total of 31 patients with advanced cutaneous squamous cell carcinoma, including 11 patients with concomitant hematologic malignancies, were enrolled and received at least one dose of nivolumab.

The median age of patients was 80 years (range 66-92 years), and the majority of patients were male (71%).

Enrolled patients received nivolumab 240 mg intravenously over 30 minutes every 2 weeks for 2 years.

The primary endpoint of the trial is investigator-assessed objective response rate (ORR) according to RECISTv1.1 criteria. Secondary endpoints include disease control rate (DCR), duration of partial response (PR) and above (DOR), progression-free survival (PFS), and overall survival (OS).

Test status

At enrollment, 19.4% of patients had locally advanced disease, 51.6% had locoregional metastasis, and 25.8% had distant metastatic disease. Seven patients (22.6%) had received 1 previous systemic treatment for cutaneous squamous cell carcinoma.

As of March 2021 (data cutoff), all available patients have completed the Week 24 RECIST assessment, 5 patients (16.1%) are still receiving treatment, 1 patient has completed treatment according to the protocol, and 25 patients have discontinued treatment.

Test results

1. Efficacy results

Among the 29 patients who were evaluable for response assessment, 12 patients achieved partial response and 7 patients achieved complete response. The best objective response rate (ORR) was 65.2%, the disease control rate (DCR) was 68.9%, and the median progression-free survival (PFS) was 11.1 months.

2. Safety results

Treatment-related adverse events occurred in 18 patients (58.1%), and 2 patients (6.5%) discontinued medication during treatment.

3. Subgroup analysis results

Subgroup analysis of patients with concomitant hematological malignancies (CHM) showed that the best objective response rate (ORR) was 55.6% (95% CI: 21.2%-86.3%), the disease control rate (DCR) was 66.7% (95% CI: 35.4%-87.9%), and the median progression-free survival (PFS) was 10.9 months (95% CI: 0.6-21.4).

The median overall survival (OS) in this subgroup was 20.7 months (95% CI: 6.5-35.0), but the overall median OS was not reached.

4. Conclusion

Nivolumab showed similar antitumor activity to other anti-PD-1 agents in advanced cutaneous squamous cell carcinoma.

Although objective response rates and overall survival were slightly reduced in patients with concomitant hematological malignancies (CHM), nivolumab also demonstrated efficacy in this subgroup without emerging safety signals.

Looking to the future

This trial once again confirmed the important role of PD-1 antibodies in the treatment of cutaneous squamous cell carcinoma. In addition to monotherapy, clinical trials of nivolumab combined with other drugs in the treatment of cutaneous squamous cell carcinoma are also ongoing.

Currently, treatment options for cutaneous squamous cell carcinoma are still limited, and we look forward to new treatment options that will benefit more patients in the future.

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