SABCS Posters Review Use of Biosimilars in New Contexts as Breast Cancer Therapy

As one study presented at the 2023 San Antonio Breast Cancer Symposium (SABCS) evaluated the use of circulating tumor DNA (ctDNA) for response prediction after combination therapy with a trastuzumab biosimilar, another examined the efficacy of a pertuzumab biosimilar candidate.

ctDNA as a Prognostic Tool After Combination Therapy Including a Biosimilar

The first study¹ concluded that the absence of ctDNA prior to and during neoadjuvant therapy (NAT), along with early ctDNA clearance, was associated with a higher pathological complete response (pCR) rate in patients with early breast cancer with a HER2-enriched intrinsic subtype treated with chemotherapy-free pembrolizumab plus the dual HER2 blockade of pertuzumab and a trastuzumab biosimilar.

The findings suggest that ctDNA analysis during NAT could be used for real-time monitoring of treatment response and guide escalation/de-escalation strategies. They also emphasize the necessity for further trials involving a larger number of patients and predesigned follow-up to validate the role of ctDNA in predicting tumor response and relapse.

The study included 48 patients with stage I-III HER2-positive early breast cancer. The primary objective was pCR, and ctDNA measurement was evaluated for its capability to predict tumor response to de-escalated, chemotherapy-free NAT.

Ninety-two plasma samples from 31 patients were assessed at baseline (BL), week 3 of NAT, and end of treatment (EOT). Notably, ctDNA was initially detected in 58% of patients at BL, decreasing to 9.7% at week 3 and 10% at EOT, with 83.3% showing ctDNA clearance by week 3. Patients with ctDNA-positive (ctDNA+) results at BL more frequently presented with stage II-III disease and lymph node involvement compared withg ctDNA-negative (ctDNA–) cases. The pCR rate was lower in patients with ctDNA+ results at BL (38.9% vs 76.9% in ctDNA–), week 3 (0% vs 60.7%), and EOT (33.3% vs 59.3%), and the highest pCR rate was observed in patients who remained ctDNA– throughout week 3.

Univariable analysis indicated that ctDNA at BL was predictive for pCR, with an odds ratio of 0.22. Bivariable models combining ctDNA with grade demonstrated the highest accuracy in analyses at BL (area under the curve [AUC], 0.77), week 3 (AUC, 0.79), and ctDNA change from BL to week 3 (AUC, 0.87). In conclusion, the study found that the absence of ctDNA prior to and during NAT, coupled with early ctDNA clearance, was associated with a higher pCR rate in patients with early breast cancer with a HER2-enriched intrinsic subtype treated with chemotherapy-free pembrolizumab plus dual HER2 blockade.

Safety and Efficacy of Pertuzumab Biosimilar

A multicenter, randomized, double-blind phase 3 study evaluated use of TQB2440, a pertuzumab biosimilar candidate referencing Perjeta, in patients with high-risk, HER2-positive early-stage breast cancer.²

Researchers enrolled 412 eligible patients between October 21, 2020, and November 21, 2022, who were randomly assigned to receive combination therapy of trastuzumab and docetaxel with either TQB2440 or the reference product. The primary end point was total pCR (tpCR) by independent review committee (IRC), and equivalence was established if the 90% CIs of the relative ratio were within the interval of 0.76 to 1.32.

In the intention-to-treat (ITT) population, the tpCR by IRC for the TQB2440 group and the reference pertuzumab group were 58.94% and 58.05%, respectively, with a relative ratio of 1.02 (90% CI, 0.89-1.16), falling within the predefined equivalence interval.

There was no statistically significant difference in breast pCR between the groups, and the breast conserving surgery rates were comparable. Results from the per-protocol population were consistent with those of the ITT population. The incidences of treatment-related adverse events (TRAEs) and grade 3 or higher TRAEs were similar between the TQB2440 and reference pertuzumab groups.

In conclusion, the study found that TQB2440 demonstrated equivalent efficacy and similar safety to the reference pertuzumab in patients with HER2-positive early or locally advanced breast cancer.

Reference

1. Graeser M, Kuemmel S, Gluz O, et al. Circulating tumor DNA (ctDNA) for prediction of pathologic complete response (pCR) after 12 weeks of pembrolizumab + trastuzumab + pertuzumab in HER2-enriched early breast cancer: WSG-Keyriched-1 trial. Presented at: SABCS 2023; December 5-9, 2023; San Antonio, TX. Poster PO1-15-12.

2. Zhang Q, Wang S, Li N, et al. Comparing the efficacy and safety of TQB2440 versus the reference pertuzumab for the treatment of HER2-positive early or locally advanced breast cancer: a multicenter, randomized, double-blind, parallel-controlled phase 3 trial. Presented at: SABCS 2023; December 5-9, 2023; San Antonio, TX. Poster PO1-27-01.