Chemotherapy-Free Drug Combo Shows Promise for Early Triple-Negative Breast Cancer

Triple-negative breast cancer has long been one of the most feared diagnoses in oncology. Lacking the estrogen, progesterone, and HER2 receptors that make other breast cancers targetable, it has historically been treated with blunt instruments: intensive chemotherapy regimens delivered before surgery, known as neoadjuvant therapy, in the hope of shrinking tumors and eliminating residual disease. Now a phase II clinical trial from China suggests that a carefully selected subgroup of patients may respond to an entirely different approach, one that replaces cytotoxic chemotherapy with an immunotherapy and an anti-angiogenic drug. The study, published in Breast Cancer Research and Treatment, tested neoadjuvant camrelizumab plus apatinib in patients with early-stage triple-negative breast cancer whose tumors showed evidence of pre-existing immune infiltration, and the results, while preliminary, point toward a future in which some patients could be spared the toxicities of conventional chemotherapy altogether.

The rationale behind the trial rests on a growing understanding of how tumors interact with the immune system. Camrelizumab is a humanized monoclonal antibody that blocks PD-1, a receptor on T cells that, when engaged by its ligand PD-L1, acts as a molecular brake on immune attack. Blocking PD-1 releases that brake, allowing T cells to recognize and destroy cancer cells. Apatinib, by contrast, is an oral small-molecule inhibitor of vascular endothelial growth factor receptor 2, or VEGFR2, which disrupts the signaling that tumors use to grow new blood vessels. Anti-angiogenic therapy does more than starve tumors of nutrients; at appropriately low doses it can normalize the chaotic vasculature inside tumors, improve oxygen delivery, and reverse an immunosuppressive microenvironment, making the tissue more permeable to infiltrating immune cells. Preclinical work has shown that low-dose anti-angiogenic therapy can sensitize breast tumors to PD-1 blockade, and the combination of camrelizumab and apatinib had already demonstrated activity in advanced triple-negative breast cancer in an earlier phase II trial.

The design of the new study was deliberately selective. Between December 2022 and March 2024, the researchers screened 25 patients with stage II to III triple-negative breast cancer and enrolled 14, all of whom had baseline tumor-infiltrating lymphocytes exceeding 10 percent. Tumor-infiltrating lymphocytes, or TILs, are immune cells that have already penetrated the tumor bed, and their abundance is a recognized marker of an inflamed, immunologically active tumor microenvironment. By restricting enrollment to TIL-high patients, the investigators aimed to treat those most likely to benefit from immunotherapy alone, without the immune-priming effects of chemotherapy. Participants received eight 21-day cycles of intravenous camrelizumab at 200 milligrams, or 3 milligrams per kilogram for patients weighing under 50 kilograms, combined with daily oral apatinib at 250 milligrams. The primary endpoint was the pathological complete response rate, the proportion of patients in whom no residual invasive cancer could be detected in the breast and lymph nodes at the time of surgery.

The efficacy results were modest but meaningful for a chemotherapy-free regimen. Of the 14 patients treated, 13 were evaluable for efficacy and 11 proceeded to surgery. Three of the 11 surgical patients, or 27.3 percent, achieved a pathological complete response, and the objective response rate, measured by radiographic tumor shrinkage according to RECIST criteria, was 46.2 percent among the 13 evaluable patients. Perhaps most striking was the durability of benefit: the 24-month disease-free survival rate reached 90.9 percent. Pathological complete response is a well-validated surrogate for long-term outcomes in triple-negative breast cancer, established by the landmark CTNeoBC pooled analysis, and a 27.3 percent rate falls below what is typically achieved with modern chemoimmunotherapy, but the near-complete absence of relapse among surviving patients during follow-up suggests that responders derive substantial protection.

Safety data provided some of the most encouraging findings. Treatment-related adverse events were predominantly grade 1 to 2, meaning mild to moderate in severity, and grade 3 or higher events occurred in 28.6 percent of patients. This toxicity profile compares favorably with standard neoadjuvant chemotherapy for triple-negative disease, which routinely causes severe neutropenia, hair loss, nausea, and peripheral neuropathy, and which is frequently combined with immune checkpoint inhibitors in current practice, compounding the burden. The absence of anthracyclines and taxanes also eliminates the risk of chemotherapy-related cardiac injury and secondary leukemias, long-term concerns for young breast cancer survivors. The trial’s quality-of-life assessments, using validated instruments including the EORTC QLQ-BR23 breast cancer module and the EQ-5D-5L questionnaire, reinforced the tolerability advantage of the regimen.

Context matters when interpreting these numbers. The current standard of care for high-risk early-stage triple-negative breast cancer, established by the KEYNOTE-522 trial, combines pembrolizumab with chemotherapy and has demonstrated pathological complete response rates above 60 percent along with improved event-free and overall survival, leading to guideline endorsements from both the National Comprehensive Cancer Network and the American Society of Clinical Oncology. The CamRelief trial further confirmed that camrelizumab added to neoadjuvant chemotherapy improves pathological complete response rates in Chinese patients. Against this benchmark, a 27.3 percent pathological complete response rate from immunotherapy and anti-angiogenic therapy alone is clearly not ready to replace chemoimmunotherapy for the general population. However, the trial’s TIL-enrichment strategy hints at a precision-oncology approach: if biomarkers can reliably identify the minority of patients whose tumors are already immunologically primed, a substantial fraction might avoid chemotherapy without sacrificing cure.

The exploratory biomarker work in the study adds scientific depth to the clinical findings. Transcriptomic analysis of tumor samples identified differential expression of genes involved in extracellular matrix remodeling and immune regulation between responding and non-responding patients. The extracellular matrix, the dense protein scaffold surrounding tumor cells, can physically exclude T cells and promote immunosuppression, and genes such as MMP-11 and SPP1 have been linked to macrophage polarization and poor prognosis in triple-negative breast cancer. Other work has shown that tumor-derived cytokines like Chi3l1 can induce neutrophil extracellular traps that wall off T cells. These molecular signatures may eventually serve as predictive biomarkers, allowing clinicians to determine before treatment begins which patients are likely to respond to the camrelizumab-apatinib combination and which require chemotherapy from the outset.

The study’s limitations are considerable and the authors are candid about them. With only 14 patients treated and 11 undergoing surgery, the trial was small, single-arm, and without a randomized comparator, making it impossible to exclude selection effects or to compare outcomes directly against standard therapy. The TIL threshold of greater than 10 percent, while grounded in international consensus guidelines for TIL assessment, defines a subgroup that represents only a portion of triple-negative breast cancer patients. Confidence intervals around the response estimates are correspondingly wide. Furthermore, pathological complete response, although a validated surrogate endpoint, is not identical to survival benefit, and ongoing debates in the oncology community about the adequacy of pathological response as a surrogate in immunotherapy trials, highlighted in recent analyses of distant disease-free survival data from large neoadjuvant trials, apply here as well.

Nevertheless, the trial, registered as NCT05556200, occupies an important position in a broader research movement toward chemotherapy-free treatment of immunologically hot tumors. Parallel efforts include neoadjuvant nivolumab-based dual checkpoint blockade in TIL-high triple-negative breast cancer presented at recent European oncology meetings, and the successful application of the same camrelizumab-apatinib combination in resectable non-small cell lung cancer. The convergence of these studies suggests that the chemotherapy-free paradigm is not a one-off experiment but a reproducible strategy built on a coherent biological principle: that tumors rich in infiltrating lymphocytes can be reactivated against themselves by removing immunosuppressive signals and normalizing the tumor microenvironment, without the need for cytotoxic drugs.

For patients, the immediate takeaway is one of cautious optimism rather than changed practice. Chemotherapy combined with immunotherapy remains the standard for early-stage triple-negative breast cancer, and no patient should alter treatment based on a 14-patient phase II study. But the trial demonstrates feasibility, manageable toxicity, preliminary activity, and a 90.9 percent two-year disease-free survival rate in a biomarker-selected population, providing the justification for larger, randomized studies that could ultimately define which patients qualify for chemotherapy-free care. If subsequent trials confirm these findings and validate the transcriptomic biomarkers identified by the researchers, the era in which every triple-negative breast cancer patient automatically receives chemotherapy may gradually give way to one in which treatment is tailored to the immunological fingerprint of each tumor, sparing many women the harshest burdens of cancer therapy while preserving, and perhaps improving, their chances of long-term cure.

Subject of Research: Neoadjuvant camrelizumab plus apatinib as a chemotherapy-free treatment for early-stage triple-negative breast cancer

Article Title: Efficacy, safety, and biomarker analysis of neoadjuvant camrelizumab plus apatinib as a chemotherapy-free strategy for early-stage triple-negative breast cancer: a phase II study

Article References: Tian, Z., Li, H., Deng, Y., Yao, H., Wang, Y., Jin, L., Deng, H., Chen, N., & Liu, J. (2026). Efficacy, safety, and biomarker analysis of neoadjuvant camrelizumab plus apatinib as a chemotherapy-free strategy for early-stage triple-negative breast cancer: a phase II study. Breast Cancer Research and Treatment, 219(2), Article 3. https://doi.org/10.1007/s10549-026-08066-5

Image Credits: AI Generated

DOI: 10.1007/s10549-026-08066-5

Keywords: triple-negative breast cancer, camrelizumab, apatinib, neoadjuvant therapy, immunotherapy, PD-1 inhibitor, anti-angiogenic therapy, tumor-infiltrating lymphocytes, pathological complete response, phase II trial, biomarkers, tumor microenvironment