two conclusive trials of therapeutic deescalation


Chicago, United States – Two trials of therapeutic escalation in breast cancer were presented and highlighted at the annual breast cancer conference. American Society of Clinical Oncology (ASCO) .

Chemo: no significant benefit in ≥ 70 years with a high genomic index

The benefit of adjuvant chemotherapy in addition to hormone therapy remains controversial for patients aged 70 years and older with estrogen receptor positive (ER +) and HER2-negative (HER2-) or relapsing primary breast cancer. isolated room.

In this context, the study ASTER 70s is the first multicenter therapeutic trial based on the analysis of tumor genomic signature, a reflection of the risk of relapse, to choose whether or not to perform adjuvant chemotherapy in people over 70 years[1]. The aim of the study was to evaluate the contribution of postoperative chemotherapy in addition to hormone therapy. versus hormone therapy alone in case of tumor aggression (high genomic grade).



Dr. Etienne Brain

The results were presented to the ASCO on June 7, 2022 by the Dr. Etienne Braina medical oncologist who specializes in breast cancer and elderly patient care at the Curie Institute, who also received the BJ Kennedy Award for Scientific Excellence in Oncogeriatrics from the ASCO (see box).

In this prospective trial, the researchers first assessed the tumor genomic grade index (GGI) in all patients. Then, patients with high GGI (high risk of relapse) were randomized between chemotherapy plus endocrine therapy vs. endocrine therapy alone.

Patients with low GGI did not receive chemotherapy and were followed in an observational cohort.

Physicians chose between 3 chemotherapy regimens: 4 cycles of doxorubicin / cyclophosphamide, doxorubicin / cyclophosphamide non-pegylated liposomal, or docetaxel / cyclophosphamide, administered every 3 weeks with G-CSF. Hormone therapy consisted of 5 years of aromatase inhibitor, tamoxifen, or a tolerance-related sequence.

The primary objective was to demonstrate an overall survival benefit (OS) related to chemotherapy in the intended population.

Between April 2012 and May 2016, 1,969 patients from 61 French centers and 12 Belgian centers were enrolled in the study. Of these, 1,089 (55%) were randomized in one of the two arms of the study. The median follow-up was 5.8 years at the data deadline (12/17/2021). The median age was 75 years (70-92). Tumors were ≥ pT2, pN +, isolated local relapses, histological grade III, in 56%, 46%, 11%, and 39% of cases, respectively.

No significant difference in overall survival was observed between the arms (RR 0.85 [0,64-1,13], p = 0.2538). The 4-year SG was 90.5% in the chemotherapy arm plus endocrine therapy arm and 89.7% in the endocrine therapy arm alone. The researchers were unable to identify a subgroup that benefited significantly from chemotherapy.

“This is the first time such a large-scale study has been available in a population that is usually excluded from clinical trials,” said Dr. Brain. therapeutic escalation in some of our elderly patients and on the considerable side of our attitudes, by default, without demonstration, using the same standards as in our younger patients. The mass of information gathered in Aster 70s will allow us to study the necessary adjustments and adaptations of these treatments, often over-prescribed as chemotherapy ”.

Aster 70s will allow the necessary adjustments and adaptations of these treatments, often over-prescribed as chemotherapy, to be studied.
Dr. Etienne Brain

The ASCO BJ Kennedy Geriatric Oncology Award 2022 awarded to Dr. E. Brain

This award recognizes a physician for his or her outstanding contributions to the research, diagnosis, and treatment of cancer in the elderly, and in recognition of his or her international educational and political animation.

“I am very proud of this award that has been presented to me today because it is the culmination of many years of work to care for the elderly with cancer, including breast cancer.” We need to continue to develop specific clinical research for this elderly population, ”said Dr. Etienne Brain.

Dr. Brain is the former Chair of the Breast Cancer Group at EORTC (European Organization for Research and Treatment of Cancer). He chairs the DIALOG Intergroup (GERICO / UCOG) dedicated to clinical research for elderly patients. He is also a former president of the International Society of Onco-Geriatrics (SIOG).

“I look forward to this prestigious overseas recognition that today honors Dr. Etienne Brain for his work for years at the Curie Institute,” he said. Pr Steven Le Gouilldirector of the Curie Institute Hospital Ensemble in a statement[2].

Could we do without conservative post-surgery radiation therapy from the age of 55?

Another trial of escalation in breast cancer presented at ASCO, the LIGHTwhich showed that some patients may be able to avoid radiation therapy after conservative breast surgery[3].

Adjuvant radiation therapy is usually prescribed after breast preservation surgery to reduce the risk of recurrence, but treatment is associated with both acute and long-term toxicity.

Women in this trial who did not receive radiation therapy and were treated with conservative breast surgery followed by hormone therapy had an overall survival rate of 97.2%. The local recurrence rate was 2.3%, the primary endpoint of the study.



Dr. Timothy Joseph Whelan

“Women 55 and older with low-grade luminal type A breast cancer, after conservative breast surgery and treated with hormone therapy alone, had a very low rate of local recurrence at age 5,” she said. commented the main author, the Dr. Timothy Joseph Whelan during its presentation to the ASCO [3].

Women 55 and older with low-grade luminal type A breast cancer after conservative breast surgery and treated with hormone therapy alone had a very low rate of local recurrence at 5 years of age.
Dr. Timothy Joseph Whelan

“More than 300,000.” [personnes] receive a diagnosis of invasive breast cancer in North America each year, the majority in the United States, ”said Dr. Whelan. “We estimate that these results could be applied to 10 to 15 percent of them, or about 30,000 to 40,000 women a year, who could avoid the morbidity, cost, and inconvenience of radiation therapy.”

Previously, studies have shown that local recurrence rates were low in women over the age of 60 with low-grade luminal A-type breast cancer who underwent only conservative breast surgery. Among women over the age of 70, the risk of local recurrence was about 4 to 5%. This new study shows that this option can be considered even earlier.

The LUMINA study looked at patients with breast cancer with a luminal A subtype associated with pathological clinical factors (defined as: ER ≥ 1%, PR> 20%, HER2-negative and Ki67 ≤ 13 , 25%).

The multicenter prospective cohort study included 501 patients aged 55 years and older who underwent conservative breast surgery for grade 1-2 T1N0 cancer.

The median age of the patients was 67 years, of whom 442 (88%) were over 75 years of age. The median tumor size was 1.1 cm.

The median follow-up was 5 years. The cohort was monitored every 6 months for the first 2 years and then annually.

At five years, there were 10 local recurrences, a rate of 2.3% (primary criterion); eight contralateral breast cancers (1.9%), a relapse-free survival rate of 97.3%, a disease-free survival rate of 89.9%, and an overall survival rate of 97.2% (secondary criteria).

“This is an extremely well-designed and important study,” she said Pre Penny R. Anderson (Radio-Oncology Service, Fox Chase Cancer Center, Philadelphia) particular subgroup of breast cancer patients ”.

Commenting on the study, the Dr. Julie Gralowexecutive vice president of ASCO, told Medscape Medical News : “I think there will be a discussion on how best to identify this group,” because in this study, patients were screened for Ki67, a marker of proliferation. However, the Ki67 test is not routinely performed. “Do we need this Ki67 test?” Do we need to develop guidelines on how to proceed? Is it better than if you have already had an Oncotype or MammaPrint test to see if the patient needs chemotherapy? She asks. “That’s where the discussion will take place.”

Is it better than if you have already had an Oncotype or MammaPrint test to see if the patient needs chemotherapy?
Dr. Julie Gralow

Also commenting on the study, the Dr. Deborah Axelrod (Perlmutter Cancer Center, NYU Langone, New York) praised the prospective, multicenter nature of the LUMINA study while pointing out some limitations: “Follow-up is 5 years and local recurrence of ER-positive cancers continues to increase. after 5 years, so longer-term follow-up would be important ”. In addition, she clarified that this was a one-arm study, and therefore without a comparison arm.

She added that in practice, patients may prefer a week of accelerated partial irradiation of the breast, rather than committing to 5 years of hormone therapy as this study does.

“Overall, the message for patients is that skipping radiation therapy should be seen as an option for older women with localized breast cancer with favorable characteristics and receiving hormone therapy,” he said. Dr. Axelrod.

The message for patients is that skipping radiation therapy should be considered an option for older women with localized breast cancer with favorable characteristics and receiving hormone therapy.
Dr. Deborah Axelrod

The LUMINA study was sponsored by the Canadian Breast Cancer Foundation and the Canadian Cancer Society. Dr. Whelan reported research funding from Exact Sciences (Inst). Drs Axelrod and Anderson did not report any interest. Dr. Gralow reported links of interest with Genentech, AstraZeneca, Hexal, Puma BioTechnology, Roche, Novartis, Seagen and Genomic Health.

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