An interview with:

Heather McArthur MD MPH, Clinical Director Breast Cancer, Komen Distinguished Chair Clinical Breast Research, University of Texas Southwestern Medical Center, Dallas TX

MILAN, Italy—Adjuvant therapy with a checkpoint inhibitor did not benefit patients with triple negative breast cancer in a big new study reported to the 14th European Breast Cancer Conference in Milan, Italy.

Heather McArthur MD MPH, Clinical Director of Breast Cancer and Komen Distinguished Chair in Clinical Breast Research at the University of Texas Southwestern Medical Center, Dallas TX, told the conference that the ALEXANDRA/IMpassion030 phase 3 trial failed to show a survival benefit when adjuvant atezolizumab was added to standard therapy. In Milan, she discussed the findings with Audio Journal of Oncology reporter Peter Goodwin.

Heather McArthur MD MPH:

IN: [SARAH MAXWELL] Patients with triple negative ,,OUT: …from me, Sarah Maxwell, good-bye. 10;06secs

ABSTRACT:

14th European Breast Cancer Conference Abstract no: 4

Abstract no: 1LBA, “Adjuvant chemotherapy with or without atezolizumab for stage II and III triple-negative breast cancer: final analysis of the ALEXANDRA/IMpassion030 phase 3 trial”

EBCC 2024, Wednesday 20 March, Young Investigator Innovation Award and oral abstract session, 11:00-12:55 hrs CET,.

https://cm.eortc.org/cmPortal/Searchable/ebcc14/config/Normal/#!sessiondetails/0000107210_0

https://www.ejcancer.com/article/S0959-8049(24)00177-1/fulltext

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PRESS RELEASE

Embargoed: 00.01 hrs CET, Wednesday 20 March 2024

Addition of atezolizumab to chemotherapy after surgery does not improve survival for triple negative breast cancer

— Final analysis of the ALEXANDRA/IMpassion030 phase 3 trial —

Milan, Italy: Patients with triple-negative breast cancer do not benefit from the addition of atezolizumab to their post-surgery chemotherapy treatment, according to the results of a large phase 3 clinical trial presented at the 14th European Breast Cancer Conference.

Triple negative breast cancer, so-called because the cancer cells are not fuelled by oestrogen, progesterone or the HER2 protein, is harder to treat and more likely to spread to other parts of the body.

Previous research has suggested that adding an immunotherapy treatment to chemotherapy before surgery can improve survival for this groups of patients. The new results show that including atezolizumab, a type of immunotherapy, with chemotherapy after surgery does not bring the same benefits.

The ALEXANDRA/IMpassion030 study is a phase 3 clinical trial that included 2199 people from 31 different countries with stage two or three triple negative breast cancer. Following surgery to remove their cancer, half of the patients were randomly assigned to be treated with chemotherapy plus atezolizumab, with the other half treated with chemotherapy.

The final analysis of the trial was presented by Dr Heather McArthur, an Associate Professor in the Department of Internal Medicine and Clinical Director of the Breast Cancer Program at the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center in Dallas, Texas, USA.

She said: “We know from a previous trial that including the immunotherapy treatment atezolizumab with chemotherapy prior to surgery is beneficial for patients with triple-negative breast cancer. The ALEXANDRA/IMpassion030 trial is the first study to look at the role of chemotherapy with or without atezolizumab post-surgery for early-stage triple-negative breast cancer.”

Patients have now been monitored for an average of 32 months. Researchers found no improvement for patients treated with atezolizumab after surgery compared to those not treated with atezolizumab in terms of survival and remaining free of cancer. Among the patients taking atezolizumab there were 141 (12.8%) who had a recurrence or died. Among patients not taking atezolizumab, there were 125 (11.4%) who had a recurrence or died. This equates to a hazard ratio of 1.11 for patients taking atezolizumab.

Researchers also found no benefit when looking at different sub-groups, such as patients whose cancer had spread to the lymph nodes and patients with PD-L1 positive cancer, which is used as a marker of cancers that are more likely to respond to immunotherapy.

Dr McArthur said: “This is a large international clinical trial looking at treatment for patients with triple-negative breast cancer. The results of this final analysis are important because they show that including the immunotherapy drug atezolizumab alongside chemotherapy does not help when it’s given to patients following surgery. By extension, this also highlights the importance of treating triple-negative breast cancer with chemotherapy and immunotherapy prior to surgery, as per the current standard of care.”

The final analysis also showed that the safety of atezolizumab, in terms of unwanted side effects, was consistent with other trials of the treatment. Among the patients treated with atezolizumab and chemotherapy, 54.3% experienced serious side effects. Among those treated with chemotherapy alone, 44.1% experienced serious side effects.

The co-chair of the 14th European Breast Cancer Conference is Dr Fiorita Poulakaki, Head of the Breast surgery Department at Athens Medical Center Hospital, Greece, and Vice President of Europa Donna, the European Breast Cancer Coalition, and was not involved with the research. She commented: “We always hope that testing new treatment approaches will improve patients’ outcomes. However, it’s just as important to know when a new treatment added to one that is already in use one is not beneficial, as in this case, to make sure patients aren’t subjected to a treatment that doesn’t work and may cause more side effects.

“The results of this final analysis show that chemotherapy with atezolizumab after surgery does not improve disease-free survival for early-stage triple-negative breast cancer. This research therefore highlights the importance of the current approach of treating triple negative breast cancer with chemotherapy and immunotherapy to shrink the tumour before surgery. This is vital information for surgeons and medical oncologists who treat patients with this aggressive type of cancer.”

Abstract no: 1LBA, “Adjuvant chemotherapy with or without atezolizumab for stage II and III triple-negative breast cancer: final analysis of the ALEXANDRA/IMpassion030 phase 3 trial”, Young Investigator Innovation Award and Oral abstracts, Wednesday 20 March, 11.00-12.55, Silver room.

https://cm.eortc.org/cmPortal/Searchable/ebcc14/config/Normal/#!sessiondetails/0000107210_0

1LBA LBA Oral – Adjuvant chemotherapy with or without atezolizumab for stage II and III triple-negative breast cancer: final analysis of the ALEXANDRA/ IMpassion030 phase 3 trial

1. McArthur1∙ A. Bailey2 ∙ S. Saji3 ∙ … ∙ M. Piccart18 ∙ M. Ignatiadis5 ∙ R. Gelber19 … Show more

Affiliations & NotesArticle Info

Background: Early-stage triple negative breast cancer (TNBC) is associated with a high risk of distant relapse. ALEXANDRA/IMpassion030 is a global, prospective, randomized, open-label, phase 3 trial that investigated the efficacy and safety of adjuvant atezolizumab (atezo) plus standard anthracycline/taxane chemo (atezo+chemo) versus standard anthracycline/ taxane chemo (chemo alone) in early-stage TNBC.

Material and Methods: In ALEXANDRA/IMpassion030 (NCT03498716) patients with resected stage II-III TNBC, confirmed by central pathology review, were randomized 1:1 to receive adjuvant chemo with or without atezo. Patients were stratified by type of surgery (breast conserving vs mastectomy), axillary nodal status (0 vs 1-3 vs ≥4 nodes), and centrally assessed PD-L1 status (IC0 vs IC1/2/3). Adjuvant chemo consisted of weekly paclitaxel 80 mg/m for 12 weeks followed by dose-dense anthracycline (epirubicin 90 mg/m2 or doxorubicin 60 mg/m2) and cyclophosphamide 600 mg/m2 for 4 doses every 2 weeks given concomitantly with atezo 840 mg every 2 weeks followed by maintenance atezo 1200 mg every 3 weeks until completion of 1 year of atezo or the same chemo regimen alone. The primary endpoint was invasive disease-free survival (iDFS) in the intention-to-treat population (ITT). Recruitment stopped after 2199 of the planned 2300 patients were enrolled (1101 atezo+chemo and 1098 chemo alone) on the recommendation of the independent data monitoring committee (IDMC). At the Interim Analysis (IA) with ∼25 months median follow-up and 239 iDFS events the hazard ratio (HR) for iDFS (primary endpoint) crossed the pre-specified futility boundary. The final analysis with ∼32 months median follow-up and 266 iDFS events is reported here.

Results: At the final analysis, the HRs remained stable compared to the IA for iDFS at 1.11 (0.87, 1.42) and for secondary endpoints: iDFS in the PDL1+ subset 1.00 (0.73, 1.35), iDFS in the node-positive subset 1.32 (0.97, 1.8), and overall survival 1.23 (0.87, 1.73) for the 2199 patients in the ITT population. At the final analysis, 2177 (99%) were safety-evaluable, 1567 (71.3%) had PD-L1 positive disease and 1067 (48.5%) had node-positive disease. The incidence of grade≥3 treatment related adverse events remained stable with 54.3% in the atezo+chemo arm vs 44.1% in the chemo alone arm.

Conclusions: At the final analysis, the addition of atezo to adjuvant anthracycline- and taxane-based chemo did not improve iDFS in the ITT population of stage II-III TNBC or in any of the subgroups interrogated. Safety data remain consistent with the known profile of atezo in early TNBC.

Conflict of interest: Advisory Board: Dr. McArthur has consulted for Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech/Roche, Immunomedics, Merck, OBI Pharma, Pfizer, Puma, Spectrum Pharmaceuticals, Syndax Pharmaceuticals, Peregrine, Calithera, Daiichi-Sankyo, Seattle Genetics, AstraZeneca, Gilead, Crown Bioscience, and TapImmune.

Corporate-sponsored Research: Dr. McArthur has research supported by Bristol-Myers Squibb MedImmune, LLC/AstraZeneca BTG and Merck.

1UTSW, Internal Medicine, Dallas, USA;

2Frontier Science, Inverness-Shire, United Kingdom;

3Fukushima Medical University, School of Medicine, Fukushima, Japan;

4Breast International Group, Brussels, Belgium;

5Institut Jules Bordet, Brussels, Belgium;

6Dana-Farber Cancer Institute, Boston, USA;

7Roche, Basel, Switzerland;

8Lviv State Oncology Regional Treatment and Diagnostic Center, Department of Chemotherapy, Lviv, Ukraine;

9Soonchunhyang University, Department of Oncology, Dongnam, South Korea;

10Clinique Tivoli Ducos, Medical Oncology, Bordeaux, France;

11Hospital Clinico Universitario Virgen de la Arrixaca, El Palmar, Spain;

12Frontier Science, Kingussie, United Kingdom;

13Omsk Clinical Oncology Dispensary, Department of Oncology, Omsk, Russia;

14Kanagawa Cancer Center, Department of Breast Surgery, Nakao, Japan;

15Genentech, San Francisco, USA;

16Fudan University Shanghai Cancer Center, Department of Breast Surgery, Shanghai, China;

17University of Milan, European Institute of Oncology, Milan, Italy;

18Institut Jules Bordet, Boston, USA;

19Dana-Farber Cancer Institute, Cancer Institute, Boston, USA