NCCN Adds Trastuzumab Delxtecan and Sacituzumab Gobitecan to Guidelines for HER2-Negative Breast Cancer

The National Comprehensive Cancer Network (NCCN) updated the Breast Cancer Guidelines on June 21, 2022, to help patients with HER2 low metastatic breast cancer (MBC) and triple-negative breast cancer (TNBC) or hormone receptor-positive HER2-negative diseases. Use of Tsuzumabu Gobitekan-hziy (Trastuzumab).¹

William J. Gradishar, MD, Chairman of the NCCN Breast Cancer Commission, announced that the Commission will provide guidance on antibody drug conjugates after the results of the Phase 3 TROPiCS-02 (NCT03901339) and DESTINY-Breast04 (NCT03734029) trials have been published. He said he had submitted some requests for. At the 2022 ASCO Annual Meeting. The strength of the data forced the Commission to update its recommendations.

“Insurers want to make sure they comply with NCCN guidelines so that certain drugs are approved, or certain strategies are approved,” Northwestern University School of Medicine, Fineberg School of Medicine said. OncLive^®.. “We weren’t pushed by anyone, but as long as the data was good, we felt that both of these were services to the patient. [agents were] It contains. “

TROPiCS-02 enrolled 543 patients with hormone receptor-positive, HER2-negative MBCs. These patients were relapsed / refractory after at least two systemic chemotherapy regimens for metastatic disease, including at least one anticancer hormone therapy and at least one CDK4 / 6 inhibitor. In a metastatic setting. Median follow-up was 10.2 months and median progression-free survival (PFS) was 5.5 months (95% CI, 4.2-7.0) for Sacituzumab gobitecan, compared to investigators. The chemotherapy selected was 4.0 months (95% CI, 3.1-4.4). (HR, 0.66; 95% CI, 0.53-0.83; P <.0003).²

At 6 months, 46% (n = 272) of patients receiving Sacituzumab gobitecan exacerbated the disease compared to 30% (n = 271) who received chemotherapy. I was alive without. At 12 months, the PFS rate was 21% vs. 7%, respectively.

“The changes were subtle, but are now included, especially if HER2 is low. [disease], Option, “said Gladisher. “In the case of Sacituzumab gobitecan, it’s not just people who are triple-negative. [The patient] It may be endocrine refractory. “

The findings of DESTINY-Breast04 (n = 557) were presented at the 2022 ASCO Annual Meeting and at the same time. New England Journal of Medicine..^3,4 Researchers define HER2-low status as a 1+ or 2+ immunohistochemistry score, and the in situ hybridization test is negative, representing approximately 65% ​​of breast cancer diagnoses. Overall, 88.7% of patients were hormone receptor positive and 11.3% were negative.

Trastuzumab delkistecan is a hormone receptor-positive HER2 low disease (HR, 0.51; 95% CI, 0.40-0.64; P <.0001). Median overall survival (OS) was 23.9 months (95% CI, 20.8-24.8) for trastuzumab delkistecan, compared with chemotherapy (HR, 0.64; 95% CI, 0.40-0.86;). P = .003).

Median PFS was 9.9 months for trastuzumab del kustecan across the study population compared to 5.1 months (95% CI, 4.2-6.8) for chemotherapy (HR, 0.50; 95% CI, 0.40-0.63). It was (95% CI, 9.0-11.3). ). Median OS for this group was 23.4 months (95% CI, 20.0-24.8) for trastuzumab delkistecan, compared to 16.8 months (95% CI, 14.5-20.0) for chemotherapy, ADC. (HR, 0.64; 95% CI, 0.49-0.84; P = .001).

In patients with hormone receptor-negative disease, median PFS was 8.5 months (95% CI, 4.3-11.7) for trastuzumab delkistecan and 2.9 months (95% CI, 1.4-5.1) for chemotherapy (95% CI, 1.4-5.1). HR, 0.46; 95% CI, 0.24-0.89). The median OS for the hormone receptor-negative cohort was 18.2 months (95% CI, 13.6-unpredictable) for trastuzumab delkistecan, compared to 8.3 for chemotherapy (HR, 0.48; 95% CI, 0.24). It was a month (95% CI, 5.6-20.6). -0.95).

“Especially for DESTINY-Breast 04, in large randomized trials, both PFS and overall survival were statistically significant, affecting the vast pool of patients in that HER2 low group. “Masu,” said Gradishar. “These are usually patients who receive single-agent chemotherapy and may not always work, so you have done a fairly large test by someone’s means and it has done well and the results are not subtle. We felt that agents should continue when it was fairly clear about the benefits of Trastuzumab del Kstecan. [the guidelines]..

On June 22, 2022, the European Medicines Agency (EMA) validated the application of type II variations of trastuzumab delkistecan monotherapy to adults with unresectable or metastatic HER2 low breast cancer.^Five

Verification confirms that the application has been completed and initiates a scientific review process by the Committee for Medicinal Products for Human Use (CHMP) at EMA. Type II variations represent significant changes in drug marketing approval that may have a significant impact on the quality, safety, or efficacy of the drug, but include changes in the active ingredient, intensity, or method of administration. I can’t. Formal approval is required for such changes.⁶ CHMP typically gives an opinion or requests more information about a Type II application 60 days after starting the evaluation.⁷

References

1. NCCN clinical practice guidelines in oncology (NCCN guidelines). Breast cancer. National Cancer Network. June 21, 2022. Accessed June 22, 2022
2. Main results of Rugo HS, Bardia A, MarméF, et al. TROPiCS-02: Hormone receptor positive / HER2-negative (HR + / HER2-) Sacituzumab gobitecan (SG) in patients with advanced breast cancer (Pts) ) And a randomized phase 3 trial for the treatment of physician choice (TPC). J Clin Oncol.. 2022; 40 (suppl 17): LBA1001. doi: 10.1200 / JCO.2022.40.17_suppl.LBA1001
3. Modi S, Jacot W, Yamashita T et al. Trastuzumab del Kistecan (T-DXd) and HER2 Doctor’s Choice (TPC) Treatment in Patients with Unresectable and / or Metastatic Breast Cancer (mBC) (pts): Randomized No. 1 Results of DESTINY-Breast 04, a three-phase study. J Clin Oncol.. 2022; 40 (suppl 17): LBA3. doi: 10.1200 / JCO.2022.40.17_suppl.LBA3
4. Modi S, Jacot W, Yamashita T et al. Trastuzumab delkistecan in previously treated HER2 low-advanced breast cancer. N Engl J Med.. Published online June 5, 2022. doi: 10.1056 / NEJMoa2203690
5. The trastuzumab delkistecan type II mutation application was validated by ema in patients with HR-positive and HR-negative HER2-low metastatic breast cancer. news release. Daiichi Sankyo. June 22, 2022. Accessed on June 22, 2022. https: //bit.ly/3O7un4t
6. European Medicines Agency. Type II variation. Accessed on June 22, 2022. https: //bit.ly/3OqgJJG
7. Advice on post-approval procedures of the European Medicines Agency for users of centralized procedures. June 20, 2022. Accessed on June 22, 2022. https: //bit.ly/3ybYEtt