ESMO 2021: Oncology Experts Share Game-Changing Data in Breast Cancer, Gynecologic Malignancies

The 2021 ESMO Congress, held as a virtual format for the second consecutive year, is fast approaching and isn’t holding back in terms of pivotal data across malignancies, especially in breast cancer and gynecologic cancers.

As the oncology community gets ready to embark on this year’s conference, OncLive® sat down with 2 top leaders in breast cancer and gynecologic cancers, respectively, to discuss the activity with the novel agents being presented, and the potential implications of the data.

BREAST CANCER

Daniel G. Stover, MD, assistant professor of medicine at The Ohio State University College of Medicine and the James Cancer Hospital/Solove Research Institute; and clinician at the Stefanie Spielman Comprehensive Breast Center

Event-free survival (EFS), overall survival (OS), and safety of adding veliparib (V) plus carboplatin (Cb) or carboplatin alone to neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) after ≥4 years of follow-up: BrighTNess, a randomized phase 3 trial (Abstract 119O)

In BrighTNess (NCT02032277), patients with operable TNBC are randomized to receive the addition of the PARP inhibitor veliparib and carboplatin vs carboplatin alone to neoadjuvant chemotherapy. Prior findings of the phase 3 trial showcased an improvement in pathologic complete response rates with the addition of veliparib and carboplatin to paclitaxel, followed by doxorubicin and cyclophosphamide; however, this was not the case with the addition of veliparib to carboplatin/paclitaxel.¹ The updated analysis to be presented at this year’s congress will include EFS, OS, and safety findings.

“The BrighTNess study of neoadjuvant chemotherapy for TNBC provides definitive data regarding event-free survival benefit of carboplatin addition to standard anthracycline-taxane neoadjuvant triple-negative breast cancer. It is clear that not all patients require the addition of carboplatin, and a critical next step is to identify which patients truly benefit from the addition of carboplatin, which does add toxicity. This is also relevant for KEYNOTE-522, which included carboplatin with immunotherapy.”

Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (mBC): results of the randomized phase 3 DESTINY-Breast03 study (Abstract LBA1)

In December 2019, the FDA granted an accelerated approval to fam-trastuzumab deruxtecan-nxki (Enhertu) for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received 2 or more prior anti–HER2-based regimens in the metastatic setting. The approval was based on results of the single-arm, phase 2 DESTINY-Breast 01 trial, which should encouraging clinical activity with the antibody-drug conjugate.²

At the 2021 ESMO Congress, data will be unveiled from the Destiny-Breast03 trial (NCT03529110), which is evaluating trastuzumab deruxtecan vs ado-trastuzumab emtansine (T-DM1; Kadcyla) in patients with advanced HER2-positive disease. The head-to-head comparison of 2 ADCs will reveal data related to progression-free survival (PFS) data, objective response rates (ORRs), and safety.

“DESTINY-Breast03 reflects impressive activity of trastuzumab deruxtecan (T-DXd) as second-line therapy for HER2-positive metastatic breast cancer, relative to current standard of care [ado-]trastuzumab emtansine [T-DM1]. With higher rates of interstitial lung disease with T-DXd and established efficacy of T-DXd after T-DM1 based on DESTINY-Breast01, it remains to be seen which patients benefit from T-DXd in the second line vs later.”

Final results of KEYNOTE-355: a randomized, double-blind, phase 3 study of pembrolizumab + chemotherapy vs placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC; Abstract LBA16)

Frontline pembrolizumab (Keytruda) combined with chemotherapy previously showed a significant improvement in PFS compared with placebo/chemotherapy (HR, 0.65; 95% CI, 0.49-0.86; one-sided P = .0012) in the advanced TNBC population.³ In November 2020, the FDA granted an accelerated approval to pembrolizumab for use in combination with chemotherapy in the treatment of patients with locally recurrent unresectable or metastatic whose tumors express PD-L1 (combined positive score [CPS] ≥10) as determined by an FDA-approved test.

The decision was based on the interim findings of the KEYNOTE-355 trial (NCT02819518), and the final results will showcase the data with OS and other outcome measures.

“The final results of KEYNOTE-355 provide evidence of overall survival benefit from the addition of pembrolizumab to chemotherapy for advanced TNBC. This is the first study showing overall survival benefit in the metastatic setting for TNBC—an important advance.”

GYNECOLOGIC CANCERS

Maurie Markman, MD, physician and president of Medicine and Science at Cancer Treatment Centers of America, and editor-in-chief of OncologyLive®

Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for persistent, recurrent, or metastatic cervical cancer: randomized, double-blind, phase III KEYNOTE-826 study (Abstract LBA2)

The phase 3 study (NCT03635567) is exploring pembrolizumab combined with chemotherapy with or without bevacizumab (Avastin) in patients with recurrent, persistent, or metastatic cervical cancer. Pembrolizumab is currently indicated for patients with recurrent or metastatic PD-L1–positive (combined positive score ≥1) cervical cancer with disease progression on or following chemotherapy.

In June 2021, a press release stated that the KEYNOTE-826 trial met the primary end point, demonstrating that the PD-1 inhibitor plus platinum-based chemotherapy with or without bevacizumab significantly improved survival vs platinum-based chemotherapy regimen with or without bevacizumab in the persistent, recurrent, or metastatic cervical cancer population, regardless of irrespective of PD-L1 status.⁴

“This randomized phase 3 trial examined the impact of adding pembrolizumab to standard chemotherapy (vs placebo) in recurrent, persistent, or metastatic cervical cancer with no previous chemotherapy, except for chemoradiation. The study revealed an impressive favorable impact for the addition of the checkpoint inhibitor in several clinically meaningful endpoints, including PFS and OS.”

Maintenance olaparib rechallenge in patients (pts) with ovarian carcinoma (OC) previously treated with a PARP inhibitor (PARPi): phase IIIb OReO/ENGOT Ov-38 trial (Abstract LBA33)

In the double-blind, phase 3 OReO study (NCT03106987), patients with non-mucinous platinum-sensitive relapsed ovarian cancer are retreated with the PARP inhibitor olaparib in 300-mg tablets or placebo until disease progression. The primary end point is investigator-assessed PFS.

“This is the first reported randomized trial designed specifically to examine the impact of retreatment with a PARP inhibitor for patients previously treated with this class of agents and who continue to have evidence of platinum-sensitivity. Additional information regarding [homologous recombination deficiency] status will be presented.”

In breast cancer, as well as in gastrointestinal and lung cancers, a live, virtual satellite symposium will take place on Tuesday, September 21, 2021. Leveraging Antibody-Drug Conjugates in Cancer Care: Evolving Approaches to Bridge Clinical Gaps in Breast, GI, and Lung Tumors is hosted by Physicians’ Education Resource® (PER. Register now to attend the event from 10:30 to 12:00 PM CEST, as well as other activities by PER).

References

1. Loibl S, O’Shaughnessy J, Untch M, et al. Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial. Lancet Oncol. 2018;19(4):497-509. doi:10.1016/S1470-2045(18)30111-6
2. Modi S, Saura C, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Eng J Med. 2020;382(7):610-621. doi:10.1056/NEJMoa1914510
3. Cortes J, Cescon DW, Rugo HS. KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. J Clin Oncol. 2020;38(suppl 15):1000. doi:10.1200/JCO.2020.38.15_suppl.1000
4. Merck announces phase 3 KEYNOTE-826 trial met dual primary endpoints of overall survival (OS) and progression-free survival (PFS) in patients with persistent, recurrent or metastatic cervical cancer. News release. Merck. June 22, 2011. Accessed June 22, 2021. https://bit.ly/3qj6SKP