Overview
This multicentre, randomized controlled trial evaluates the effect and safety of acupuncture combing with PD-1 inhibitors plus chemotherapy in NSCLC. Participants will be randomly assigned to undergo either acupuncture or sham acupuncture concurrent with the initial four-six cycles of chemotherapy combined with PD-1 inhibitors.
Description
This multicenter, randomized controlled clinical trial designed to evaluate the efficacy and safety of electro-acupuncture (EA) as an adjunctive therapy, combined with PD-1 inhibitors and chemotherapy, as a first-line treatment for advanced NSCLC. This trial plans to enroll 424 patients with advanced NSCLC who are negative for actionable driver gene mutations, including but not limited to EGFR and ALK, and a PD-L1 tumor proportion score (TPS) below 50%. Through a central randomization system, participants will be allocated in a 1:1 ratio to either the EA group or the sham-acupuncture control group. The intervention will be administered concurrently with the induction-phase chemotherapy combined with PD-1 inhibitor therapy, for a total of 4 to 6 cycles.
The primary endpoint is progression-free survival (PFS), defined as the time from randomization to the first documented disease progression or death. Secondary efficacy endpoints include overall survival (OS), objective response rate (ORR), disease control rate (DCR), and duration of response (DoR). The symptom burden and health-related quality of life, will be assessed using the Lung Cancer Symptom Scale (LCSS) and the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) with its lung cancer-specific module (QLQ-LC13). Safety and tolerability will be evaluated based on the incidence, severity, and causality of adverse events, graded according to the Common Terminology Criteria for Adverse Events (CTCAE). Immune-related adverse events (irAEs) will be specifically managed per the NCCN Guidelines for Management of Immunotherapy-Related Toxicities. Efficacy analyses will be performed on the full analysis set (FAS) following the intention-to-treat (ITT) principle. Sensitivity analyses will be conducted on the per-protocol set (PPS) to assess the robustness of the primary findings.
Eligibility
Inclusion Criteria:
- Pathologically confirmed NSCLC, with AJCC lung cancer TNM stage IV.
- Tumor proportion score for PD-L1 \< 50%.
- Lacks targetable gene mutations (including but not limited to EGFR mutations or ALK fusions).
- No prior systemic therapy for advanced NSCLC (including chemotherapy, targeted therapy, or immunotherapy). Patients planned to receive first-line (induction) treatment with ICIs plus chemotherapy are eligible. Patients who have received prior neoadjuvant or adjuvant therapy, or definitive chemoradiotherapy, may be enrolled if provided that disease progression occurred more than 6 months after the completion of the last treatment.
- ECOG performance status score of 0-2.
- Age ≥ 18 years.
- At least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
- Adequate organ function (hematology: ANC ≥ 1500/mcL, PLT ≥ 100,000/mcL, Hb ≥ 9.0 g/dL or ≥ 5.6 mmol/L; renal function: estimated creatinine clearance ≥ 50 mL/min; hepatic function: serum total bilirubin ≤ 1.5 × ULN or total bilirubin \> 1.5 × ULN with direct bilirubin ≤ ULN, AST and ALT ≤ 2.5 × ULN ≤ 5 × ULN for patients with liver metastases).
- Voluntary participation in the study, signed informed consent form, good compliance, and cooperation with follow-up.
Exclusion Criteria:
- Inability to complete baseline assessments.
- Pregnant or lactating women, and those with psychiatric, intellectual, or language disorders.
- Patients with autoimmune diseases or hematologic disorders requiring long-term use of hormones or immunosuppressants.
- Presence of concurrent primary malignant tumors at other sites.
- Participation in another investigational drug or device clinical trial within 30 days prior to the planned initiation of study treatment.
- Known seropositivity for human immunodeficiency virus (HIV), other congenital or acquired immunodeficiencies, or history of organ or stem cell transplantation (including autologous bone marrow or peripheral blood stem cell transplantation).
- Loss of self-care capacity, or any medical, psychological, or ethical condition that, in the investigator's judgment, could interfere with the patient's ability to complete the study.
- Active skin infection, ulceration, or lesion at acupuncture point sites that would preclude safe administration of treatment.
- Implanted cardiac pacemaker or other active implantable electronic medical device.
- Severe needle phobia that would prevent acceptance of needling procedures required by the study protocol.
- Receipt of any acupuncture or related needle-based therapy within 6 weeks prior to enrollment.
- Active pneumonitis, or radiation pneumonitis requiring treatment with systemic corticosteroids.
- Active infection requiring antimicrobial therapy (antibacterial, antifungal, or antiviral agents) according to clinical guidelines at the time of screening. Enrollment may be reconsidered after the infection has been adequately controlled.
- Active tuberculosis infection, or any severe or uncontrolled systemic illness, including but not limited to clinically significant neurological conditions (e.g., uncontrolled seizures, dementia), unstable or decompensated respiratory, cardiac, hepatic, or renal disease.
