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What we haven’t [had] until now were the long-awaited overall survival data. This is only a key secondary end point, but it’s of course, from a patient perspective, the most important end point.”

Peter Schmid, MD, PhD, FRCP, professor, cancer medicine, Barts Cancer Institute, Queen Mary University of London, discusses the updated long-term overall survival (OS) results from the phase 3 KEYNOTE-522 trial (NCT03036488), which evaluated pembrolizumab (Keytruda) plus chemotherapy in patients with high-risk, early-stage triple-negative breast cancer (TNBC). Updated data were presented at the 

The KEYNOTE-522 trial assessed pembrolizumab in combination with neoadjuvant chemotherapy followed by surgery and adjuvant pembrolizumab or placebo for patients with high-risk, early-stage TNBC. Schmid explains that earlier results showed that the addition of pembrolizumab to chemotherapy significantly increased pathologic complete response (pCR) rates by approximately 30.6%, with a pCR rate of 64.8% (95% CI, 59.9%-69.5%) vs 51.2% (95% CI, 44.1%-58.3%) in the placebo arm (estimated treatment difference, 13.6%; 95% CI, 5.4%-21.8%; 

At a median follow-up of 75.1 months (range, 65.9-84.0), the 60-month event-free survival (EFS) rate was statistically significant in favor of the pembrolizumab plus chemotherapy arm, at 81.2% compared with 72.2% in the placebo plus chemotherapy arm (HR, 0.65; 95% CI, 0.51-0.83), Schmid reports.

Additionally, the proportion of patients experiencing an EFS event, such as recurrence, progression, or death, was lower in the pembrolizumab group, at 20.3% compared with 29.2% in the placebo group. These results underscore the long-term benefit of pembrolizumab in combination with chemotherapy for patients with high-risk, early-stage TNBC, Schmid notes.

Furthermore, the 5-year OS rates were 86.6% (95% CI, 84.0%-88.8%) in the pembrolizumab arm vs 81.7% (95% CI, 77.5%-85.2%) in the placebo arm (HR, 0.66; 95% CI, 0.50-0.87; 

= .00150). In total, 14.7% of patients in the pembrolizumab arm had an OS event vs 21.8% of those in the placebo arm.

Schmid concludes that these long-term data further solidify the role of pembrolizumab as part of the standard treatment strategy for this patient population.

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Peter Schmid, MD, PhD, FRCP, discusses updated KEYNOTE-522 data showing that pembrolizumab plus chemotherapy improves EFS in early-stage TNBC.

Dr Schmid on Pembrolizumab Plus Chemotherapy in High-Risk, Early-Stage TNBC

Dr Schmid on the Use of Perioperative Pembrolizumab in TNBC

Peter Schmid, MD, PhD, clinical director, Breast Cancer Centre, honorary consultant medical oncologist, St. Bartholomew’s Hospital; chair, Cancer Medicine, lead, Centre of Experimental Cancer Medicine, leader, Academic Breast Cancer Programme, Barts Cancer Institute, Queen Mary University, discusses updated event-free survival findings from the phase 3 KEYNOTE-522 trial (NCT03036488) of neoadjuvant pembrolizumab (Keytruda) plus chemotherapy followed by adjuvant pembrolizumab in patients with early-stage triple-negative breast cancer. 

, Schmid presented 5-year follow-up data from 

. Five years is an important time point in TNBC, because recurrences tend to occur early, Schmid notes. Approximately 65% to 70% of all recurrences in patients with TNBC happen within the first 3 years, and approximately 80% to 90% of recurrences occur within the first 5 years, Schmid explains.

In KEYNOTE-522, at a median follow-up of 63.1 months, the EFS rate was 81.3% in patients who received pembrolizumab vs 72.3% in those who received placebo (HR, 0.63; 95% CI, 0.49-0.81). This long-term follow-up analysis also showed relative and absolute EFS benefits with perioperative pembrolizumab plus chemotherapy vs placebo plus chemotherapy across several patient subgroups. In patients with stage II disease, the EFS rates were 85.6% and 77.5%, respectively (HR, 0.59; 95% CI, 0.43-0.82). In those with stage III disease, the EFS rates were 68.2% and 57.1%, respectively (HR, 0.71; 95% CI, 0.48-1.05). Furthermore, 76.8% of patients with node-positive disease who received pembrolizumab were event free vs 67.0% of those who received placebo (HR, 0.67; 95% CI, 0.49-0.93). Among patients with node-negative disease, the EFS rates were 86.3% and 77.8% in the pembrolizumab and placebo arms, respectively (HR, 0.56; 95% CI, 0.38-0.84).

Moreover, in patients with T2N0 tumors, the EFS rates with pembrolizumab vs placebo were 87.8% vs 77.9%, respectively (HR, 0.49; 95% CI, 0.31-0.78). This finding demonstrates that patients with small cancers have significantly improved outcomes when they receive pembrolizumab as part of their neoadjuvant treatment, Schmid concludes.

Dr Schmid reports consulting fees from Eli Lilly & Company and Gilead Science.

Peter Schmid, MD, PhD, discusses updated event-free survival findings from the phase 3 KEYNOTE-522 trial of neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab in patients with early-stage triple-negative breast cancer. 

Peter Schmid, MD, PhD, FRCP, professor of cancer medicine, Royal College of Physicians, clinical director, Breast Cancer Centre, honorary consultant medical oncologist, St. Bartholomew’s Hospital, chair, Cancer Medicine, lead, Centre of Experimental Cancer Medicine, Barts Cancer Institute, discusses additional results from the phase 3 KEYNOTE-522 trial (NCT03036488) in early-stage triple-negative breast cancer (TNBC). 

The KEYNOTE-522 trial randomized patients with early-stage TNBC to receive neoadjuvant pembrolizumab (Keytruda) plus chemotherapy vs placebo plus chemotherapy, followed by adjuvant pembrolizumab vs placebo. Initial findings from the study revealed that pembrolizumab/chemotherapy followed by pembrolizumab led to a statistically significant and clinically meaningful improvement in event-free survival (EFS) vs placebo/chemotherapy followed by placebo.

During the 2021 San Antonio Breast Cancer Symposium, updated findings from the study were presented, demonstrating robust treatment benefit with the experimental regimen in an EFS sensitivity analysis. Moreover, the benefit was observed irrespective of nodal status, overall disease stage, menopausal status, HER2 status, and lactate dehydrogenase. 

Ultimately, these findings confirm the utility of neoadjuvant and adjuvant pembrolizumab across a wide spectrum of patients with early-stage TNBC and underscore the importance of conducting sensitivity and subgroup analyses in clinical trials, concludes Schmid. 

Peter Schmid, MD, PhD, FRCP, discusses additional results from the phase 3 KEYNOTE-522 trial in early-stage triple-negative breast cancer.  



Dr. Schmid on Additional Results From the KEYNOTE-522 Trial in Early-Stage TNBC 

Peter Schmid, MD, PhD, lead at the Centre for Experimental Cancer Medicine, Barts Cancer Institute, discusses the evaluation of biosimilars in oncology.

It is important to assess each and every biosimilar within the context of the trials they have been studied in, says Schmid. One has to consider the plausibility that there may be differences between the biologic and the biosimilar. However, if the data do indicate the similarity of the agents, there is no reason why they should not be used in practice. Ultimately, the use of biosimilars will have to be discussed on a case-by-case basis, says Schmid.

Notably, the National Health Service in the United Kingdom has started to introduce biosimilars for trastuzumab (Herceptin). Most recently, on June 13, 2019, ABP 980 (Kanjinti; trastuzumab-anns), a trastuzumab (Herceptin) biosimilar, was approved by the FDA in the United States for patients with HER2-overexpressing breast cancer and HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. This marks the fifth regulatory approval for a trastuzumab biosimilar.

Dr. Schmid on Evaluating Biosimilars in Oncology

Peter Schmid, MD, PhD, lead at the Centre for Experimental Cancer Medicine, Barts Cancer Institute, discusses the role of biosimilars in oncology.

Biosimilars play an increasingly important role in the treatment of patients with cancer. There is a specific pathway that has been established by regulatory agencies that a biosimilar must go through in order to demonstrate bioequivalence. Despite initial hesitance regarding the similarity between a biologic and a biosimilar, provider comfort has grown since biosimilars for granulocyte-colony stimulating factor agents and trastuzumab (Herceptin) have become available.

In June 2019, the FDA approved ABP 980 (Kanjinti; trastuzumab-anns), a trastuzumab biosimilar, for the treatment of patients with HER2-overexpressing breast cancer as well as HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, marking the fifth approval by the agency for a trastuzumab biosimilar. Ultimately, the introduction of biosimilars have had a positive impact on a global scale, says Schmid. However, some challenges still need to be addressed, he concludes.

Dr. Schmid on the Role of Biosimilars in Oncology

Peter Schmid, MD, PhD, lead at the Centre for Experimental Cancer Medicine, Barts Cancer Institute, discusses challenges with biosimilars in oncology.

One of the main challenges that exist in bringing biosimilars to market is their demonstration of bioequivalence to the reference product, says Schmid. Furthermore, some of the confidence intervals for demonstrated equivalence are wide, making it difficult to discern a potential detriment or difference with a biosimilar.

There is a possibility that biosimilars may be more effective than their biologic counterparts, he adds. Even if the same antibody is used to the construct the product, its interaction with a patient’s immune system may manifest differently as a result of glycosylation. Increasing data point to the fact that the activity of antibody-based therapy is triggered through the immune system, leading to further skepticism surrounding the idea of similarity, especially in the curative setting. However, regulatory agencies are in place to ensure that trials are conducted appropriately to assess similarity and produce robust data.

Dr. Schmid on Challenges Concerning Biosimilars in Oncology

Peter Schmid, MD, PhD, lead at the Centre for Experimental Cancer Medicine, Barts Cancer Institute, discusses the phase Ib study of pembrolizumab (Keytruda) in combination with chemotherapy for patients with triple negative breast cancer (TNBC).

The KEYNOTE-173 trial (NCT02622074) is a 6-cohort, phase Ib study of neoadjuvant platinum/taxane chemotherapy in combination with pembrolizumab in patients with locally advanced TNBC. The study sought to determine the safety and tolerability as well as establish a recommended phase II dose for further evaluation.

Sixty patients enrolled, with a median age of 48.5 years (26-71). Patients received 9 cycles of therapy prior to surgery, approximately 3 to 6 weeks later. To be eligible, women ≥18 years had to have a new diagnosis of locally advanced, treatment-naïve TNBC, with an ECOG score of 0 or 1, and stable organ function. Median follow-up was 19.6 months (4.0-27.4 months). At the time of data cutoff, 78.3% patients completed neoadjuvant therapy and 21.7% discontinued treatment.

Dr. Schmid on the Design and Findings of the KEYNOTE-173 Trial in TNBC

Peter Schmid, MD, PhD, lead at the Centre for Experimental Cancer Medicine, Barts Cancer Institute, discusses findings from the IMpassion130 trial in triple-negative breast cancer (TNBC).

The phase III IMpassion130 trial evaluated the efficacy and safety of the PD-L1 inhibitor atezolizumab (Tecentriq) plus nab-paclitaxel (Abraxane) versus nab-paclitaxel alone in treatment-naïve patients with metastatic TNBC. Findings presented at the 2018 ESMO Congress showed that the addition of atezolizumab to nab-paclitaxel reduced the risk of progression or death by 38% compared with nab-paclitaxel alone in patients with PD-L1—positive disease.

The median progression-free survival in the PD-L1—positive population was 7.5 months (95% CI, 6.7-9.2) with atezolizumab plus nab-paclitaxel and 5.0 months (95% CI, 3.8-5.6) with chemotherapy (HR, 0.62; 95% CI, 0.49-0.78; 

 <.0001). Schmid says the addition of atezolizumab to nab-paclitaxel established a clear benefit in this population. At the time of presentation, the overall survival analysis was not statistically significant, but in the PD-L1—positive patients, there was an increase in benefit with the addition of a checkpoint inhibitor.

Peter Schmid, MD, PhD

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