首个鳞状NSCLC全覆盖：KEYTRUDA联合卡双药化疗正式获批
意料之中不再赘述
FDA Approves Merck’s KEYTRUDA® (pembrolizumab) in Combination with Carboplatin and Either Paclitaxel or Nab-Paclitaxel for the First-Line Treatment of Patients with Metastatic Squamous Non-Small Cell Lung Cancer (NSCLC)
Approval Based on Results of Phase 3 KEYNOTE-407 Trial, Which Demonstrated Superior Overall Survival with KEYTRUDA in Combination with Chemotherapy Compared to Chemotherapy Alone
First Anti-PD-1 Approved for First-Line Treatment of Squamous NSCLC Regardless of PD-L1 Expression
生存和缓解数据如下
之前K药单药或者联合获批的NSCLC适应症也覆盖了鳞癌，但是：1）PD-L1表达有限制，KN-024是针对PD-L1 ≥50%，，KN-042是针对PD-L1 ≥1%，漏掉了PD-L1 <1%，2）样本量，042中还好接近40%，但是024中只有18%的鳞癌
而在407里，不管是OS和PFS，Keytruda+Chemo都受益
安全性事件上没有新的不良事件，虽然K+chemo组因治疗引起的终止比例比对照组高些，但整体比例并不高
IO单药及联合一线NSCLC格局
KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with carboplatin and either paclitaxel or nab-paclitaxel, for the first-line treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC) based on results from the KEYNOTE-407 trial. In the pivotal Phase 3 trial of patients regardless of tumor PD-L1 expression status, KEYTRUDA in combination with chemotherapy (carboplatin and either paclitaxel or nab-paclitaxel) significantly improved overall survival (OS), reducing the risk of death by 36 percent compared to chemotherapy alone (HR=0.64 [95% CI, 0.49, 0.85]; p=0.0017). This approval marks the first time an anti-PD-1 regimen has been approved for the first-line treatment of squamous NSCLC regardless of tumor PD-L1 expression status.
“Today’s approval expands our current lung cancer indications to include combination treatment in patients with squamous cell carcinoma, a type of lung cancer that is particularly difficult to treat,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. “Approval by the FDA has the potential to mean that KEYTRUDA can be used to improve survival for more patients with this debilitating disease.”
Immune-mediated adverse reactions, which may be severe or fatal, can occur with KEYTRUDA, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation (HSCT). Based on the severity of the adverse reaction, KEYTRUDA should be withheld or discontinued and corticosteroids administered if appropriate. KEYTRUDA can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. For more information, see “Selected Important Safety Information” below.
“The results that support this approval from the KEYNOTE-407 trial demonstrate the potential of KEYTRUDA in combination with chemotherapy in patients with squamous non-small cell lung cancer, regardless of PD-L1 expression,” said Dr. Balazs Halmos, director of the multidisciplinary thoracic oncology program at the Montefiore Einstein Center for Cancer Care and director of clinical cancer genomics at the Albert Einstein College of Medicine. “With this important approval, more patients will have the opportunity to benefit from immunotherapy.”
KEYTRUDA is the first anti-PD-1 approved in the first-line setting as both combination and monotherapy in certain patients with metastatic NSCLC (see KEYTRUDA indications below). With this approval, all appropriate patients with metastatic squamous NSCLC and all appropriate patients with metastatic nonsquamous NSCLC and no EGFR or ALK genomic tumor aberrations are now eligible for a KEYTRUDA-based regimen as their first-line treatment option.
Data Supporting the Approval
The approval was based on data from KEYNOTE-407, a randomized, double-blind, multicenter, placebo-controlled study. The key eligibility criteria for this study were metastatic squamous NSCLC, regardless of tumor PD-L1 expression status, and no prior systemic treatment for metastatic disease. Patients with autoimmune disease that required systemic therapy within two years of treatment; a medical condition that required immunosuppression; or who had received more than 30 Gy of thoracic radiation within the prior 26 weeks were ineligible. Patients were randomized to receive KEYTRUDA 200 mg and carboplatin every three weeks for four cycles, plus paclitaxel every three weeks for four cycles or nab-paclitaxel on Days 1, 8 and 15 of every three-week cycle for four cycles, followed by KEYTRUDA 200 mg every three weeks; or placebo and carboplatin every three weeks for four cycles, plus paclitaxel every three weeks for four cycles or nab-paclitaxel on Days 1, 8 and 15 of every three-week cycle for four cycles, followed by placebo every three weeks.
Treatment with KEYTRUDA or placebo continued until progression of disease, unacceptable toxicity, or a maximum of 24 months. Patients in the placebo arm were offered KEYTRUDA as a single agent at the time of disease progression.
Primary efficacy outcome measures were OS as well as progression-free survival (PFS) and objective response rate (ORR) as assessed by blinded independent central review (BICR) using RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ. An additional efficacy outcome measure was duration of response.
In KEYNOTE-407, there was a statistically significant improvement in OS, PFS and ORR in patients randomized to KEYTRUDA in combination with carboplatin and either paclitaxel or nab-paclitaxel compared with patients randomized to placebo with carboplatin and either paclitaxel or nab-paclitaxel.