EMA Recommends Six New Oncology Indications in January and February

Since the beginning of the year, the European Medicines Agency (EMA) has issued six positive opinions recommending new indications for treatments in oncology, with a heavy focus on new treatments for lung cancer. These agents have previously been approved by the United States (US) Food and Drug Administration (FDA). Final approval in the European Union will depend on ruling by the European Commission.

  • Dacomitinib, Another EGFR Inhibitor for NSCLC. The EMA recommended approval for the pan-human epidermal growth factor receptor (EGFR)- targeting tyrosine kinase inhibitor (TKI) dacomitinib (Vizimpro®, Pfizer) for first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) who carry EGFR activating mutations. This recommendation for approval was based on results from the phase III ARCHER 1050 trial, which compared dacomitinib to gefitinib in previously untreated patients with EGFR-mutated NSCLC. Dacomitinib resulted in a significant improvement in progression-free survival (PFS) compared to gefitinib (14.7 months vs 9.2 months; HR 0.59, P<.0001). In addition, treatment with dacomitinib prolonged median overall survival (OS) by 7 months (34.1 months vs 26.8 months; HR 0.76; P = .0438).
  • Lorlatinib Recommended for ALK-Positive NSCLC. The anaplastic lymphoma kinase (ALK) inhibitor lorlatinib (Lorviqua®, Pfizer) was recommended for approval for the treatment of patients with ALK-positive NSCLC that have progressed on at least one prior ALK-targeted TKI. In a phase II trial, lorlatinib resulted in an objective response rate (ORR) of 47.0% in ALK-positive patients who had previously been treated with at least one ALK TKI. Importantly, lorlatinib demonstrated activity against central nervous system (CNS) metastases, with a 63.0% intracranial response rate in patients with measurable baseline CNS lesions.
  • Atezolizumab Plus Bevacizumab and Chemotherapy for NSCLC. The combination of atezolizumab and bevacizumab (Tecentriq® and Avastin®, Roche) along with paclitaxel and carboplatin chemotherapy was recommended for approval as a first-line treatment for patients with metastatic nonsquamous NSCLC. This recommendation was based on the phase III IMPower150 trial, in which this combination resulted in a prolonged median PFS (8.3 months vs 6.8 months; HR 0.51, P<.001) and median OS (19.2 months vs. 14.7 months; HR 0.78; P = .02) compared to bevacizumab plus chemotherapy alone. Patients with EGFR or ALK mutations should receive appropriate targeted therapy prior to receiving this combination.
  • Two New Indications for Pembrolizumab. The PD-1 inhibitor pembrolizumab (Keytruda®, Merck Sharp & Dohme) was recommended for new indications in NSCLC and melanoma. In both indications, pembrolizumab was recommended for use in patients, regardless of PD-L1 expression status.
    • In NSCLC, the indication was expanded to include first-line treatment in combination with carboplatin and paclitaxel or nab-paclitaxel in patients with metastatic squamous NSCLC. This new indication is supported by results from the Keynote-407 trial, in which the combination of pembrolizumab and chemotherapy resulted in a 4.6 month improvement in OS compared to chemotherapy alone (15.9 months vs 11.3 months; HR 0.64, P<.001).
    • In melanoma, the indication of pembrolizumab was expanded to include use as adjuvant therapy following complete resection in patients with stage III melanoma and lymph node involvement. In the Keynote-054 trial, adjuvant therapy with pembrolizumab resulted in a significant improvement in the rate of recurrence-free survival (RFS) at 1 year compared to placebo (75.4% vs 61.0%; HR 0.57, P<.001).
  • Green Light for Olaparib in BRCA-Associated Breast Cancer. The indication of the poly(ADP ribose) polymerase (PARP) inhibitor olaparib (Lynparza®, AstraZeneca) was expanded to include use as a monotherapy in patients with HER2-negative locally advanced or metastatic breast cancer who carry germline BRCA1/2 mutations and who have previously been treated with an anthracycline and a taxane in the (neo)adjuvant or metastatic setting. Patients with hormone receptor-positive breast cancer should have progressed on or after prior endocrine therapy or be considered unsuitable for endocrine treatment. In the phase III OlympiAD trial, olaparib resulted in a 7.0 month PFS, compared to 4.2 months for physician’s choice of standard therapy (HR 0.58, P<.001).

EMA-Positive-Opinions-Jan-2019