Atezolizumab Approved as Adjuvant Treatment for Non-Small Cell Lung Cancer
Atezolizumab has been approved for adjuvant treatment following resection and platinum-based chemotherapy in patients with Stage II-IIIA non-small cell lung cancer (NSCLC) whose tumors have PD-L1 expression on >= 1 percent of tumor cells, as determined by an FDA-approved test. The FDA also approved the VENTANA PD-L1 (SP263) assay as a companion diagnostic device to select patients with NSCLC for adjuvant treatment with atezolizumab.
The major efficacy outcome measure was disease-free survival (DFS) as assessed by the investigator in the primary efficacy analysis population (n=476) of patients with Stage II-IIIA NSCLC with PD-L1 expression on >=1 percent of tumor cells (PD-L1 >=1% TC). Median DFS was not reached (95% CI: 36.1, NE) in patients on the atezolizumab arm compared with 35.3 months (95% CI: 29.0, NE) on the BSC arm (HR 0.66; 95% CI: 0.50, 0.88; p=0.004).
In a pre-specified secondary subgroup analysis of patients with PD-L1 TC >= 50 percent Stage II-IIIA NSCLC, the DFS HR was 0.43 (95% CI: 0.27, 0.68). In an exploratory subgroup analysis of patients with PD-L1 TC 1-49 percent Stage II-IIIA NSCLC, the DFS HR was 0.87; (95% CI: 0.60, 1.26).
The most common (>=10%) adverse reactions in patients receiving atezolizumab, including laboratory abnormalities, were increased aspartate aminotransferase, blood creatinine, and alanine aminotransferase, as well as hyperkalemia, rash, cough, hypothyroidism, pyrexia, fatigue/asthenia, musculoskeletal pain, peripheral neuropathy, arthralgia, and pruritus.
The recommended atezolizumab dose for this indication is 840 mg every 2 weeks, 1,200 mg every 3 weeks, or 1,680 mg every 4 weeks for up to 1 year.
Pembrolizumab Combination Approved for First-Line Treatment of Cervical Cancer
Pembrolizumab in combination with chemotherapy, with or without bevacizumab, was approved for patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS >=1), as determined by an FDA-approved test.
FDA also granted regular approval to pembrolizumab as a single agent for patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS >=1) as determined by an FDA-approved test. In June 2018, FDA had granted accelerated approval to this indication with the companion diagnostic, PD-L1 IHC 22C3 pharmDx.
KEYNOTE-826 (NCT03635567), a multicenter, randomized, double-blind, placebo-controlled trial, examined pembrolizumab with paclitaxel and cisplatin or paclitaxel and carboplatin, with or without bevacizumab. The trial enrolled 617 patients with persistent, recurrent, or first-line metastatic cervical cancer who had not been treated with chemotherapy. Patients were enrolled irrespective of PD-L1 expression status. Patients were randomized (1:1) to one of two treatment groups: pembrolizumab 200 mg plus chemotherapy with or without bevacizumab or placebo plus chemotherapy with or without bevacizumab. Pembrolizumab was continued until disease progression, unacceptable toxicity, or 24 months of treatment.
The main efficacy outcome measures were overall survival (OS) and progression-free survival (PFS) assessed by the investigator using RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ. Additional outcome measures were ORR and duration of response (DoR). For patients with tumors expressing PD-L1 (CPS >=1, N=548), the median OS was not reached (95% CI: 19.8, NR) in the pembrolizumab arm and was 16.3 months (95% CI: 14.5, 19.4) in the placebo arm (HR 0.64; 95% CI: 0.50, 0.81; 1-sided p=0.0001). Median PFS was 10.4 months (95% CI: 9.7, 12.3) in the pembrolizumab arm and 8.2 months (95% CI: 6.3, 8.5) in the placebo arm (HR 0.62; 95% CI: 0.50, 0.77; 1-sided p< 0.0001). The objective response rates were 68 percent (95% CI: 62, 74) and 50 percent (95% CI: 44, 56) with median DoR of 18.0 and 10.4 months in the pembrolizumab and placebo arms, respectively.
The most common adverse reactions (>=20%) in patients treated with pembrolizumab, chemotherapy, and bevacizumab were peripheral neuropathy, alopecia, anemia, fatigue/asthenia, nausea, neutropenia, diarrhea, hypertension, thrombocytopenia, constipation, arthralgia, vomiting, urinary tract infection, rash, leukopenia, hypothyroidism, and decreased appetite.
The recommended pembrolizumab dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months.
FDA Approves Abemaciclib With Endocrine Therapy for Early Breast Cancer
The FDA approved abemaciclib with endocrine therapy (tamoxifen or an aromatase inhibitor) for adjuvant treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence and a Ki-67 score >=20 percent, as determined by an FDA-approved test. This is the first CDK 4/6 inhibitor approved for adjuvant treatment of breast cancer. The FDA also approved the Ki-67 IHC MIB-1 pharmDx assay as a companion diagnostic for selecting patients for this indication.
Efficacy was evaluated in monarchE (NCT03155997), a randomized (1:1), open-label, two-cohort multicenter trial that included adult women and men with HR-positive, HER2-negative, node-positive, resected, early breast cancer with clinical and pathological features consistent with a high risk of disease recurrence. Patients were randomized to receive either 2 years of abemaciclib plus their physician's choice of standard endocrine therapy or standard endocrine therapy alone.
The major efficacy outcome measure was invasive disease-free survival (IDFS). In patients with high risk of recurrence and Ki-67 score >=20 percent (N=2003), the trial demonstrated a statistically significant improvement in IDFS (HR 0.626; 95% CI: 0.488, 0.803; p=0.0042). IDFS at 36 months was 86.1 percent (95% CI: 82.8, 88.8) for patients receiving abemaciclib plus tamoxifen or an aromatase inhibitor and 79.0 percent (95% CI: 75.3, 82.3) for those receiving tamoxifen or an aromatase inhibitor. Overall survival data were not mature at the time of the IDFS analysis.
The most common adverse reactions (>=20%) were diarrhea, infections, neutropenia, fatigue, leukopenia, nausea, anemia, and headache.
The recommended abemaciclib starting dose is 150 mg taken twice daily in combination with tamoxifen or an aromatase inhibitor until completion of 2 years of treatment or until disease recurrence, or unacceptable toxicity.