热烈祝贺辉瑞！FDA加速批准第三代ALK抑制剂lorlatinib上市！非小细胞肺癌患者的福音！

今天，辉瑞公司（纽约证券交易所股票代码：PFE）宣布，美国食品药品监督管理局（FDA）已批准其LORBRENA®（lorlatinib），一种第三代间变性淋巴瘤激酶（ALK）酪氨酸激酶抑制剂（TKI） ，针对ALK阳性转移性非小细胞肺癌（NSCLC）的患者，他们在接受克唑替尼和至少一种其它ALK抑制剂治疗之后疾病发生恶化，或接受艾乐替尼（alectinib）或色瑞替尼（ceritinib）作为第一个ALK抑制剂治疗但疾病恶化。

FDA根据肿瘤反应率和反应持续时间加速批准该适应症。对该适应症的持续批准可能取决于验证临床试验中对临床益处的验证。 这是辉瑞公司在两个月内获得FDA批准的第三款肿瘤疗法，这三款中包括两种肺癌药物。

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药时代将继续密切关注，及时报道！

U.S. FDA Approves LORBRENA® (lorlatinib) for Previously-Treated ALK-Positive Metastatic NSCLC

• LORBRENA Addresses Unmet Needs for Certain Patients Treated With Prior ALK Therapy

November 02, 2018 04:42 PM Eastern Daylight Time

NEW YORK--(BUSINESS WIRE)--Pfizer Inc. (NYSE:PFE) today announced that the U.S. Food and Drug Administration (FDA) has approved LORBRENA® [lor-BREN-ah] (lorlatinib), a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) for patients with ALK-positive metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on crizotinib and at least one other ALK inhibitor for metastatic disease; or whose disease has progressed on alectinib or ceritinib as the first ALK inhibitor therapy for metastatic disease. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. This represents the third FDA approval Pfizer has received for an oncology treatment, including two lung cancer medicines, within two months.

“Over the years, Pfizer has transformed research, management and treatment for patients with ALK-positive non-small cell lung cancer. Building upon our extensive understanding of tumor complexity and treatment resistance, LORBRENA was discovered by Pfizer scientists and developed specifically to inhibit tumor mutations that may drive resistance to other ALK tyrosine kinase inhibitors,” said Andy Schmeltz, Global President, Pfizer Oncology. “We believe that LORBRENA will benefit patients with ALK-positive metastatic non-small cell lung cancer that have progressed on prior therapy and continue to deliver on our commitment to addressing unmet needs of cancer patients.”

Since Pfizer introduced XALKORI® (crizotinib) as the first TKI for the treatment of ALK-positive metastatic NSCLC in 2011, the availability of these medicines has created an opportunity to provide patients with treatment options other than chemotherapy. However, lung cancer remains the leading cause of cancer-related death around the world.

While many ALK-positive metastatic NSCLC patients respond to initial TKI therapy, they typically experience tumor progression.1,2Additionally, options for patients who progress after treatment with second-generation ALK TKIs, alectinib, brigatinib and ceritinib, are limited.3 The approval of LORBRENA represents a new option for patients who have progressed on a second-generation ALK TKI, providing an opportunity to remain on oral therapy.

“The last decade has witnessed dramatic improvements in the treatment of metastatic ALK-positive non-small cell lung cancer due to earlier generation ALK biomarker-driven therapies. Yet almost all patients still relapse due to drug resistance, with a large proportion of patients developing new or worsening brain metastases,” said Alice T. Shaw, MD, PhD, Professor of Medicine at Harvard Medical School, and Director of the Center for Thoracic Cancers at Massachusetts General Hospital. “In a clinical study which included patients with or without brain metastases, LORBRENA demonstrated clinical activity in patients with metastatic ALK-positive non-small cell lung cancer who had failed other ALK biomarker-driven therapies.”

The approval was based on a non-randomized, dose-ranging and activity-estimating, multi-cohort, multicenter Phase 1/2 study, B7461001, evaluating LORBRENA for the treatment of patients with ALK-positive metastatic NSCLC, who were previously treated with one or more ALK TKIs. A total of 215 patients with ALK-positive metastatic NSCLC were enrolled across various subgroups based on prior treatment. Among these patients, overall response rate (ORR) was 48 percent (95% CI: 42%, 55%) and importantly, 57 percent had previous treatment with more than one ALK TKI. In the trial, 69 percent of patients had a history of brain metastases and intracranial response rate was 60 percent (95% CI: 49%, 70%).

“Since leading with the first approval of a biomarker-driven treatment for ALK-positive non-small cell lung cancer in 2011, Pfizer scientists and clinicians have remained committed to researching and developing medicines that can further advance the care of these patients,” said Mace Rothenberg, MD, Chief Development Officer, Oncology, Pfizer Global Product Development. “LORBRENA’s approval is an important milestone for patients, having demonstrated marked activity in a study that included a broad range of individuals with ALK-positive non-small cell lung cancer. This includes patients who were heavily pretreated and facing limited options after receiving first- and second-generation ALK tyrosine kinase inhibitors.”

Among 295 ALK-positive or ROS1-positive metastatic NSCLC patients who received LORBRENA 100 mg once daily in study B7461001, the most common (≥ 20%) adverse reactions were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea. The most common (≥20%) laboratory abnormalities were hypercholesterolemia, hypertriglyceridemia, anemia, hyperglycemia, increased AST, hypoalbuminemia, increased ALT, increased lipase, and increased alkaline phosphatase. Serious adverse reactions occurred in 32 percent of the 295 patients. The most frequent serious adverse reactions reported were pneumonia (3.4%), dyspnea (2.7%), pyrexia (2%), mental status changes (1.4%), and respiratory failure (1.4%). Fatal adverse reactions occurred in 2.7 percent of patients and included pneumonia (0.7%), myocardial infarction (0.7%), acute pulmonary edema (0.3%), embolism (0.3%), peripheral artery occlusion (0.3%), and respiratory distress (0.3%). Permanent discontinuation of LORBRENA for adverse reactions occurred in eight percent of patients; approximately 48 percent of patients required dose interruptions and 24 percent required at least one dose reduction. The full prescribing information for LORBRENA can be found here.

Pfizer is committed to ensuring that patients living with lung cancer have access to this innovative therapy. Patients in the U.S. who are prescribed LORBRENA have access to Pfizer Oncology TogetherTM, which offers personalized patient support including financial assistance and additional resources to help them manage day-to-day life with their condition.

About LORBRENA® (lorlatinib)

LORBRENA is indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on crizotinib and at least one other ALK inhibitor for metastatic disease; or whose disease has progressed on alectinib or ceritinib as the first ALK inhibitor therapy for metastatic disease.

This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

LORBRENA is currently approved in Japan for the treatment of ALK fusion gene-positive unresectable advanced and/or recurrent non-small cell lung cancer with resistance or intolerance to ALK tyrosine kinase inhibitor(s).

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