3중 음성 유방암 환자 치료용으로 아테졸리주맙 승인

3중 음성 유방암 환자 치료용으로 아테졸리주맙이 승인을 받았습니다

"2019년 11월 27일 The Lancet Oncology"에서 발표된 IMpassion130 평가의 업데이트된 연구 결과는 위약 및 나브파클리탁셀을 받은 환자와 조합하여 attzolizumab을 받은 환자들의 수명은 개선되지 않았다는 것을 보여주었습니다.

그러나 종양이 PD-L1 단백질의 발현에 양성 반응을 보인 환자들의 경우, 아톨리주맙 치료 환자의 전체 생존 중위수는 납-파클리탁셀과 위약을 받은 환자의 18개월과 비교했을 때 25개월입니다. 그러나, 실험의 통계적 설계 때문에, 연구자들은 통계적으로 유의한 차이를 공식적으로 선언할 수 없었다고 설명했습니다.

그럼에도 불구하고, 이번 연구에 동행한 사설에서, 텍사스 대학교 MD 앤더슨 암 센터의 웬디 우드워드 박사는 "이번 발견은 삼중 음성 유방암에서 면역 치료제 결합에 대한 열정에 확고한 타당성을 부여하고 향후 진보를 위한 프레임워크를 제공합니다"라고 썼다.

3월 8일, 식품의약품안전청은 삼중 음성 유방암을 앓고 있는 일부 여성들의 초기 치료를 위해 화학요법과 함께 면역치료제인 아톨리주맙(테센트리크)에 대한 가속 승인을 허가했습니다.

복합요법은 면역요법을 포함한 유방암 치료의 첫 번째 FDA 승인 요법입니다. 가속화된 승인은 환자가 치료의 혜택을 받는다는 것을 강력히 시사하는 연구의 초기 데이터를 기반으로 합니다. 가속화된 승인 하에, FDA는 치료법이 임상적 이점을 가지고 있는지 확인하기 위해 제약 제조 업체에 추가 연구를 수행하도록 요구합니다.

이 승인은 화학요법 약물 나브-파클리탁셀(Abraxane)과 함께 사용되는 etzolizumab에 대한 것입니다. 이 조합은 수술로 치료할 수 없는 국소적으로 발달했거나 전이성 삼중 음성 유방암을 앓고 있는 여성들에게 승인되었고, 종양이 PD-L1이라고 불리는 단백질에 양성인 여성들에게 승인되었습니다.

FDA는 또한 VENTANA PD-L1 (SP142) Assay라고 불리는 동반 진단 테스트를 승인했는데, 이 테스트는 면역 치료-치매 치료 조합으로 치료 대상인 삼중 음성 유방암 환자를 식별하는 데 사용되어야 합니다.

Attzolizumab은 면역 체크포인트 억제제로 알려진 약의 종류에 속합니다. 이 약들은 PD-L1이나 PD-1과 같은 면역 체크포인트 단백질을 억제함으로써 면역체계에 "브레이크를 해제"하여 면역세포가 암세포를 찾아 공격하는 능력을 향상시킵니다.

임상 시험 결과입니다.

FDA의 승인은 3상성 유방암 환자에 대한 치료 초기, 즉 1선으로 위약 플러스 나브파클락셀을 위약 플러스 나브파클락셀과 비교한 3상 IMpassion130 임상시험Exit Regoverage의 결과에 근거한 것입니다.

재판에는 국소적으로 진행되거나 전이성 3중성 유방암 환자 902명이 포함됐는데, 이 환자는 전이성 질환에 대한 사전 항암치료나 표적치료를 받지 못했습니다.

PD-L1–양성종양 임상시험에서 369명의 환자 중 중간 진행 없는 생존은 식졸리주맙 치료 환자의 경우 7.4개월, 위약과 화학요법을 병행한 환자의 경우 4.8개월로 나타났습니다.

목표 응답률은 위약 그룹의 33%인 etzolizumab 그룹에서 53%였다.

레이샤 A씨는 "조합치료의 혜택을 받은 환자가 PD-L1–양성종양 환자라는 것은 재판 결과에서 매우 명백했다"며 "이들은 PD-L1–양성종양 환자였다"고 말했다. 미국 피츠버그대 메디컬센터 힐만 암센터와 마제 여성병원의 에멘스 박사, 재판의 선임 조사관 중 한 명입니다.

에멘스 박사는 "3중 음성 유방암에서 PD-L1은 종양에 침투하는 면역세포에 주로 표현된다"며 "이는 면역치료제 약물과 환자들에게 화학요법을 실험하는 근거의 일부를 제공했다"고 말했다.

2019년 3월 28일 : 국립암센터 제공

Atezolizumab Approved for Some Patients with Triple-Negative Breast Cancer

March 28, 2019, by NCI Staff

UPDATE: Updated findings from the IMpassion130 trial—published November 27, 2019, in The Lancet Oncology—showed that there was no improvement in how long patients who received atezolizumab in combination with nab-paclitaxel lived compared with those who received a placebo and nab-paclitaxel.

However, in patients whose tumors tested positive for expression of the PD-L1 protein, the median overall survival of atezolizumab-treated patients was 25 months compared with 18 months for those who received nab-paclitaxel and a placebo. But, because of the statistical design of the trial, the researchers explained that they were unable to formally declare that difference statistically significant.

Even so, in an editorial that accompanied the study, Wendy Woodward, M.D., Ph.D., of the University of Texas MD Anderson Cancer Center, wrote that “the finding solidly gives validity to the enthusiasm for immunotherapy combinations in triple-negative breast cancer and provides a framework for future progress.”

On March 8, the Food and Drug Administration (FDA) granted an accelerated approval for the immunotherapy drug atezolizumab (Tecentriq) in combination with chemotherapy for the initial treatment of some women with advanced triple-negative breast cancer.

The combination therapy is the first FDA-approved regimen for breast cancer to include immunotherapy. Accelerated approvals are based on early data from studies which strongly suggest that patients benefit from a treatment. Under accelerated approvals, FDA requires the drug manufacturer to conduct additional studies to confirm that the therapy has a clinical benefit.

The approval is for atezolizumab used in combination with the chemotherapy drug nab–paclitaxel (Abraxane). The combination is approved for women with locally advanced or metastatic triple-negative breast cancer that cannot be treated surgically and whose tumors are positive for a protein called PD-L1.

FDA also approved a companion diagnostic test called the VENTANA PD-L1 (SP142) Assay, which must be used to identify patients with triple-negative breast cancer who are candidates for treatment with this immunotherapy–chemotherapy combination.

Atezolizumab belongs to a class of drugs known as immune checkpoint inhibitors. By inhibiting immune checkpoint proteins such as PD-L1 or PD-1, these drugs “release the brakes” on the immune system, enhancing the ability of immune cells to find and attack cancer cells.

Clinical Trial Results

FDA’s approval was based on results from the phase 3 IMpassion130 clinical trialExit Disclaimer, which compared atezolizumab plus nab-paclitaxel with placebo plus nab-paclitaxel as the initial, or first-line, treatment for patients with triple-negative breast cancer.

The trial included 902 patients with locally advanced or metastatic triple-negative breast cancer who had not received prior chemotherapy or targeted therapy for metastatic disease.

Among the 369 patients in the trial with PD-L1–positive tumors, the median progression-free survival was 7.4 months for patients treated with atezolizumab plus chemotherapy and 4.8 months for those who received placebo plus chemotherapy.

The objective response rate was 53% in the atezolizumab group versus 33% for the placebo group.

“It was very clear from the trial results that the patients who benefited from the combination therapy were those with PD-L1–positive tumors,” said Leisha A. Emens, M.D., Ph.D., of the University of Pittsburgh Medical Center Hillman Cancer Center and Magee Women's Hospital, one of the trial’s lead investigators.

In triple-negative breast cancer, PD-L1 is expressed mainly on immune cells that infiltrate tumors, Dr. Emens said, noting that this provided part of the rationale for testing an immunotherapy drug plus chemotherapy in patients.

"Adding chemotherapy to immunotherapy has been successful in other cancers,” she said. “The idea is that chemotherapy can break open cancer cells and release proteins that immune cells can then recognize and use to attack the tumor.”

The clinical trial was sponsored by the manufacturer of atezolizumab, Roche/Genentech.

A Difficult-to-Treat Disease

“This is a possible therapeutic option for patients with a subtype of breast cancer that is difficult to treat,” said Jung-Min Lee, M.D., in the Women’s Malignancies Branch of NCI’s Center for Cancer Research, who was not involved in the study.

“There are no specific targeted drugs for patients with triple-negative breast cancer, and recurrence is common,” Dr. Lee continued. “Once it recurs, the disease is very difficult to treat.”

The increase in median progression-free survival is a “meaningful” improvement for patients, said Dr. Lee, noting that the combination was well tolerated. “Patients want to have not only an improved quantity of life but also a good quality of life.”

The most common side effects in the atezolizumab group included hair loss, peripheral neuropathy, cough, fever, fatigue, neutropenia, and nausea. There was also more hypothyroidism in the atezolizumab group, but doctors could manage this side effect, Dr. Emens noted.

Dr. Lee cautioned, however, that even among the patients whose tumors expressed PD-L1, there were some who did not respond well to the atezolizumab–chemotherapy combination, including those patients with advanced disease that had spread to the liver, lung, or bone.

Future Research

“I’m excited about this new approach, but as clinicians, we have to use the combination therapy wisely,” Dr. Lee said.

Doctors need to consider the risks and benefits of using the combination to treat patients with advanced disease who have certain metastases, as well as patients who have mutations in the BRCA1 or BRCA2 gene, she continued.

Additional clinical trials are needed to inform future discussions between patients and physicians about using the combination treatment, Dr. Lee added.

“We also need to develop immunotherapy-based strategies for the group of patients whose tumors are not PD-L1–positive,” said Dr. Emens. Another goal for future research is to test immunotherapy-based treatments earlier in the course of the disease, she added.