Clinical Practice Recommendations Published For Immunotherapy to Treat Breast Cancer

Contemporary Concepts | <b>Contemporary Concepts in Breast Cancer</b>

The Society for Immunotherapy of Cancer published clinical practice guidelines for treating patients with breast cancer using immunotherapy.

The Society for Immunotherapy of Cancer (SITC) recently published the first clinical practice guidelines focusing on immunotherapy as treatment for patients with breast cancer utilizing a panel of leaders in immunotherapy and breast oncology along with patient advocates and breast cancer survivors.1

“Immunotherapy is now offering some patients with breast cancer clinically meaningful benefit in early-stage and advanced disease,” Jennifer Litton, MD, chair of the SITC Breast Cancer Immunotherapy Guideline Expert Panel, said in a press release.2 “It is important for clinicians and patients to understand that immunotherapy is very different from traditional breast cancer treatments, and this new guideline offers the expert guidance needed to safely consider these treatments.”

In the guidelines published in the Journal for ImmunoTherapy of Cancer, SITC used the Institute of Medicine’s (IOM) Standards for Developing Trustworthy Clinical Practice Guidelines as a model to develop the recommendations, which suggests the development of an expert panel. The recommendations made by panelists were based on both literature evidence and clinical experience when each were appropriate. Consensus agreements were determined via open communication and scientific debate, surveys, and formal voting among panelists. Minimum threshold for agreement among the panelists was 75%.

Treating TNBC With PD-L1 Inhibitors

The expert panel focused the early portion of its recommendations on the use PD-L1 inhibitors for patients with advanced/metastatic and early-stage/locally advanced breast cancer. For patients in either category, the recommendations suggest clinical trial enrollment be undertaken when available to help further understanding of the benefits of checkpoint inhibition in breast cancer.

Because therapy benefit might be contingent upon tumor properties such as PD-L1 status, patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) are recommended for PD-L1 testing in tumor tissue using an FDA-approved assay as well as comprehensive genomic profiling for aspects such as high tumor mutational burden (TMB) and microsatellite instability (MSI).

Based on a clinically significant improvement in progression-free survival (PFS) for patients with frontline TNBC treated with pembrolizumab (Keytruda) versus placebo in the KEYNOTE-355 (NCT02819518)3, which resulted in accelerated approval for the PD-1 inhibitor in combination with chemotherapy for advanced/metastatic PD-L1–positive disease,4 the guidelines suggest its use plus either nab-paclitaxel (Abraxane), paclitaxel, or carboplatin and gemcitabine as a viable first-line treatment for patients with this disease and PD-L1-positive tumors with a combined positive score (CPS) of 10 or more as determined via the 22C3 assay.

Panelists also recommended atezolizumab (Tecentriq) and nab-paclitaxel as a first-line therapeutic option for untreated TNBC with tumor-infiltrating immune cells expressing PD-L1 in 1% or more of cells based on clinical results from the IMpassion130 trial (NCT02425891).5 Specifically, median PFS was 7.2 months for patients in the atezolizumab group compared with 5.5 months for patients treated with matched placebo (HR, 0.80; 95% CI, 0.69-0.92; P = .002).

Among other things, the panelists recommend nab-paclitaxel be the only chemotherapy backbone used in combination with atezolizumab for patients with locally advanced/metastatic TNBC and PD-L1–positive tumors. Although the ideal chemotherapy backbone is unknown in this setting, research from the phase 3 IMpassion131 trial (NCT03125902) of atezolizumab plus paclitaxel versus matched placebo did not indicate a stastically significant PFS (HR, 0.82; 95% CI, 0.60-1.12; P = .2) or OS (HR 1.12, 95% CI 0.76-1.65) benefit in a population of patients with PD-L1–TNBC.6

Neoadjuvant Treatment for TNBC

Pembrolizumab plus chemotherapy is the only neoadjuvant treatment approved by the FDA for patients with high-risk early-stage TNBC at the time these guidelines were written, according to the authors. Adding pembrolizumab to standard neoadjuvant chemotherapy improved estimated pathologic complete response (pCR) rates, regardless of PD-L1 status, in the phase 2 I-SPY 2 trial (NCT01042379).7

Because of these data and event-free survival results from the phase 3 KEYNOTE-522 trial (NCT03036488),8 pembrolizumab plus chemotherapy in the neoadjuvant setting and continuing as a single-agent adjuvant treatment after surgery in patients with high-risk early-stage TNBC is a standard of care. For this cohort of patients, the benefits and toxicities of adjuvant immunotherapy must be weighed.

Recommendations for Future Treatment

Looking ahead, the panelists recommend that understanding of both short- and long-term toxicities be emphasized in existing and future studies involving immunotherapy combination approaches.

“Breast cancer has historically been a disease for which immunotherapy was largely unavailable,” SITC President, Patrick Hwu, MD, said in a press release. “The new clinical practice guideline is the first to be published by SITC on breast cancer and is the twelfth manuscript published in SITC’s Cancer Immunotherapy Guidelines series. This guideline serves as vital resource for oncologists managing the various unexpected adverse events that may arise with treatment. This is a pivotal step forward for SITC as the world leader in advancing the science and application of cancer immunotherapy and demonstrates a continued commitment to ensuring that breast cancer patients have the most optimal outcomes while receiving FDA-approved immunotherapies.”


  1. Emens LA, Adams S, Cimino-Mathews A, et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of breast cancer. J Immunother Cancer. 2021;9(8):e002597. doi:10.1136/jitc-2021-002597
  2. Society for Immunotherapy of Cancer Publishes Clinical Practice Guideline on Immunotherapy for the Treatment of Breast Cancer. News release. Society for Immunotherapy of Cancer. Published August 18, 2021. Accessed August 26, 2021.
  3. Cortes J, Cescon DW, Rugo HS, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396(10265):1817-1828. doi:10.1016/S0140-6736(20)32531-9
  4. FDA grants accelerated approval to pembrolizumab for locally recurrent unresectable or metastatic triple negative breast cancer. News release. FDA. Published November 13, 2021. Accessed September 10, 2021.
  5. Schmid P, Adams S, Rugo HS, et al. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2018;379(22):2108-2121. doi:10.1056/NEJMoa1809615
  6. Miles DW, Gligorov J, André F, et al. Primary results from IMpassion131, a double-blind placebo-controlled randomised phase III trial of first-line paclitaxel (PAC) ± atezolizumab (atezo) for unresectable locally advanced/metastatic triple-negative breast cancer (mTNBC). Ann Oncol. 2020;31(suppl 4):LBA15. doi:10.1016/j.annonc.2020.08.2243
  7. Nanda R, Liu MC, Yau C, et al. Effect of Pembrolizumab Plus Neoadjuvant Chemotherapy on Pathologic Complete Response in Women With Early-Stage Breast Cancer: An Analysis of the Ongoing Phase 2 Adaptively Randomized I-SPY2 Trial. JAMA Oncol. 2020;6(5):676-684. doi:10.1001/jamaoncol.2019.6650
  8. Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020;382(9):810-821. doi:10.1056/NEJMoa1910549