# 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

Source: https://onco.cc/key-papers/paper-i-spy-2-jama-oncol-2020/  
OnCo record `paper-i-spy-2-jama-oncol-2020` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Published report from the I-SPY 2 trial registered as NCT01042379, in JAMA Oncology (2020), chosen as the most cited paper whose own text cites the registry id.

## Summary

Importance: Approximately 25% of patients with early-stage breast cancer who receive (neo)adjuvant chemotherapy experience a recurrence within 5 years. Improvements in therapy are greatly needed.

Objective: To determine if pembrolizumab plus neoadjuvant chemotherapy (NACT) in early-stage breast cancer is likely to be successful in a 300-patient, confirmatory randomized phase 3 neoadjuvant clinical trial.

Design, setting, and participants: The I-SPY2 study is an ongoing open-label, multicenter, adaptively randomized phase 2 platform trial for high-risk, stage II/III breast cancer, evaluating multiple investigational arms in parallel. Standard NACT serves as the common control arm; investigational agent(s) are added to this backbone. Patients with ERBB2 (formerly HER2)-negative breast cancer were eligible for randomization to pembrolizumab between November 2015 and November 2016.

Interventions: Participants were randomized to receive taxane- and anthracycline-based NACT with or without pembrolizumab, followed by definitive surgery.

Main outcomes and measures: The primary end point was pathologic complete response (pCR). Secondary end points were residual cancer burden (RCB) and 3-year event-free and distant recurrence-free survival. Investigational arms graduated when demonstrating an 85% predictive probability of success in a hypothetical confirmatory phase 3 trial.

Results: Of the 250 women included in the final analysis, 181 were randomized to the standard NACT control group (median [range] age, 47 [24.77] years). Sixty-nine women (median [range] age, 50 [27-71] years) were randomized to 4 cycles of pembrolizumab in combination with weekly paclitaxel followed by AC; 40 hormone receptor (HR)-positive and 29 triple-negative. Pembrolizumab graduated in all 3 biomarker signatures studied. Final estimated pCR rates, evaluated in March 2017, were 44% vs 17%, 30% vs 13%, and 60% vs 22% for pembrolizumab vs control in the ERBB2-negative, HR-positive/ERBB2-negative, and triple-negative cohorts, respectively. Pembrolizumab shifted the RCB distribution to a lower disease burden for each cohort evaluated. Adverse events included immune-related endocrinopathies, notably thyroid abnormalities (13.0%) and adrenal insufficiency (8.7%). Achieving a pCR appeared predictive of long-term outcome, where patients with pCR following pembrolizumab plus chemotherapy had high event-free survival rates (93% at 3 years with 2.8 years' median follow-up).

Conclusions and relevance: When added to standard neoadjuvant chemotherapy, pembrolizumab more than doubled the estimated pCR rates for both HR-positive/ERBB2-negative and triple-negative breast cancer, indicating that checkpoint blockade in women with early-stage, high-risk, ERBB2-negative breast cancer is highly likely to succeed in a phase 3 trial. Pembrolizumab was the first of 10 agents to graduate in the HR-positive/ERBB2-negative signature.

Trial registration: ClinicalTrials.gov Identifier: NCT01042379.

Indexed on Europe PMC as PubMed record 32053137 (DOI 10.1001/jamaoncol.2019.6650). Its abstract cites the registry id NCT01042379, which is how it was matched to this trial; no figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: JAMA Oncology
- Year: 2020
- DOI: 10.1001/jamaoncol.2019.6650
- Authors: Nanda R, Liu MC, Yau C, et al.
- What it means: This is the paper Europe PMC returns for registry id NCT01042379 with the most citations, so it is the natural first reading for anyone following the I-SPY 2 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Caveats: Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.

## Sources

- JAMA Oncol 2020: https://doi.org/10.1001/jamaoncol.2019.6650
- PubMed: https://pubmed.ncbi.nlm.nih.gov/32053137/
- Europe PMC: https://europepmc.org/article/MED/32053137
- ClinicalTrials.gov NCT01042379: https://clinicaltrials.gov/study/NCT01042379

## Connected records

- trials: [I-SPY 2](https://onco.cc/trials/i-spy-2/), [I-SPY 2.2](https://onco.cc/trials/i-spy-2-2/)
- journals: [JAMA Oncology](https://onco.cc/journals/jama-oncology/)

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