“Among the notable updates in the National Comprehensive Cancer Network’s (NCCN) recently released treatment guidelines for non–small cell cancer (NSCLC) is the category 2A recommendation to give osimertinib (Tagrisso), a third-generation irreversible EGFR inhibitor designed to inhibit both EGFR-sensitizing and EGFR T790M-resistance mutations, in the first-line setting for patients whose disease is EGFR mutant, explains Suresh A. Ramalingam, MD.
“Osimertinib was also given a category 1 recommendation as a subsequent therapy after patients progressed on treatment with standard EGFR tyrosine kinase inhibitors (TKIs) erlotinib (Tarceva), gefitinib (Iressa), and afatinib (Gilotrif). The FDA granted a breakthrough therapy designation to a supplemental biologics license application for osimertinib as a frontline treatment for patients with metastatic EGFR-mutation–positive NSCLC in October 2017. The application was based on findings from the double-blind, phase III FLAURA trial, in which frontline osimertinib was associated with a 54% reduction in the risk of progression or death compared with standard therapy.”
“Combination regimens—particularly with checkpoint inhibitors and chemotherapy—are showing promise for the treatment of patients with squamous non–small cell lung cancer (NSCLC).
“Beyond the May 2017 FDA approval of pembrolizumab (Keytruda) plus carboplatin/pemetrexed for nonsquamous patients regardless of PD-L1 status, researchers are turning their focus to immunotherapy combinations in squamous patients in ongoing clinical trials. For example, the randomized, open-label, phase III IMpower131 study is evaluating the safety and efficacy of atezolizumab (Tecentriq) in combination with carboplatin/paclitaxel or carboplatin/nab-paclitaxel (Abraxane) versus carboplatin/nab-paclitaxel in chemotherapy-naïve patients with stage IV squamous NSCLC (NCT02367794). The trial, which has a primary endpoint of progression-free survival, is expected to enroll 1021 patients.”
“Immune checkpoint inhibitors have significantly reshaped the treatment landscape of advanced non-small cell lung cancer (NSCLC) in the second-line and, more recently, in the first-line setting. However, only a subset of patients achieves a durable response on immunotherapy, and it is not clear whether prior immunotherapy treatment impacts response to salvage chemotherapy.
“A recent retrospective study evaluated responses to salvage chemotherapy in 73 patients with advanced NSCLC who had progressed on prior PD-1/PD-L1 inhibitors. Ten of the 73 patients had received immunotherapy as first-line treatment, while the remaining 63 patients had received immunotherapy as second-line treatment following first-line chemotherapy. Response to salvage chemotherapy was compared to response to the last chemotherapy administered before immunotherapy (LCBI).”
“In topline results announced from the phase III IMpower150 trial, atezolizumab (Tecentriq) in combination with bevacizumab (Avastin) and chemotherapy delayed progression or death when compared with bevacizumab and chemotherapy alone for patients with advanced nonsquamous non–small cell lung cancer (NSCLC).
“The co-primary endpoints for the IMpower150 study were progression-free survival (PFS) and overall survival (OS). Although exact numbers have not yet been released, Roche, the manufacturer of the anti–PD-L1 and anti–VEGF agents, called the reduction in progression or death with the addition of atezolizumab a ‘clinically meaningful reduction’ in a press release. At the interim analysis, data for OS were not yet mature, with the company labeling the findings as ‘encouraging.’ ”
“European regulators are allowing earlier use of Janssen’s Zytiga in the treatment pathway for metastatic prostate cancer.
“Zytiga (abiraterone) plus prednisone/prednisolone has been approved to treat newly-diagnosed high-risk metastatic hormone-sensitive prostate cancer (mHSPC) in adult men in combination with androgen deprivation therapy (ADT).
“The drug is already available in Europe for metastatic castration-resistant prostate cancer (mCRPC) in adults who are asymptomatic or mildly symptomatic after failure of ADT in whom chemotherapy is not yet clinically indicated and in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen.”
“New results again demonstrated the benefit of frontline osimertinib (Tagrisso) in patients with EGFR-positive advanced non–small cell lung cancer (NSCLC) and CNS metastases at baseline, according to data presented at the 2017 ESMO Asia Congress.
“The subgroup analysis from the phase III FLAURA trial included 128 patients with at least 1 measurable and/or nonmeasurable CNS lesion at baseline. Among 61 patients who received osimertinib, the CNS objective response rate (ORR) was 66%, compared to 43% (odds ratio, 2.5; 95% CI 1.2-5.2; P = .011) in 67 patients who received standard EGFR TKI therapy with erlotinib (Tarceva) or gefitinib (Iressa).”
“The addition of atezolizumab to first-line treatment with bevacizumab and chemotherapy significantly prolonged PFS among individuals with advanced nonsquamous non-small cell lung cancer, according to the agent’s manufacturer.
“The randomized, multicenter, open-label phase 3 IMpower150 study assessed the efficacy and safety of atezolizumab in combination of chemotherapy with or without bevacizumab (Avastin, Genentech) for patients with stage IV nonsquamous NSCLC who had not undergone chemotherapy for their advanced disease.”
“The addition of bevacizumab to adjuvant chemotherapy failed to improve survival outcomes in patients with surgically resected early-stage non–small-cell lung cancer (NSCLC), according to a new randomized trial. The agent “does not have a role” in this setting, the investigators concluded.
” ‘In the setting of advanced-stage NSCLC, the first agent to improve survival when added to a platinum doublet was bevacizumab,’ wrote authors led by Heather A. Wakelee, MD, of the Stanford Cancer Institute at Stanford University in California. The researchers tested whether the VEGF-targeted agent would be similarly effective in the early-stage NSCLC adjuvant setting, where patients remain at high risk of relapse despite chemotherapy.”
“AstraZeneca’s Faslodex has been cleared on both sides of the Atlantic for use in combination with a CDK4/6 inhibitor.
“In the EU, the drug’s use has been approved for use alongside the CDK4/6 inhibitor palbociclib to treat a certain form of breast cancer, in the US it can be prescribed in combination with the CDK4/6 inhibitor abemaciclib.
“Both the European Commission and US Food and Drug Administration have approved the combination for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) locally advanced or metastatic breast cancer in women who have received prior endocrine therapy.”