European Medicines Agency Approves Lorlatinib
March 1, 2019—The EMA has endorsed lorlatinib for the treatment of patients with ALK-positive advanced NSCLC that has progressed during prior kinase inhibitor therapy. The Committee for Medicinal Products for Human Use recommended granting of a conditional marketing authorization. Lorlatinib is recommended as monotherapy for patients who disease has progressed after first-line treatment with alectinib or ceritinib, or with crizotinib plus at least one other ALK-based TKI.
Lorlatinib was approved by the U.S. Food and Drug Administration in November 2018.
FDA Grants Priority Review to Roche’s Personalized Medicine Entrectinib
February 19, 2019—The U.S. Food and Drug Administration (FDA) accepted a New Drug Application (NDA) and granted Priority Review for entrectinib for treatment of patients with ROS-1 mutations and metastatic NSCLC. The FDA is expected to make a final decision regarding approval by mid-August 2019. Entrectinib also has received the FDA’s Breakthrough Therapy Designation, Priority Medicines designation by the European Medicines Agency (EMA), and Sakigake designation by the Japanese health authorities for the treatment of NTRK fusion-positive locally advanced or metastatic solid tumors in adult or pediatric patients who have experienced disease progression following prior therapies or have no other treatment options.
E-cigs Help Smokers Quit, Health Risks Unknown
January 30, 2019—British researchers found that e-cigarettes were more effective for smoking cessation than nicotine-replacement therapy when combined with behavioral therapy. The randomized trial, the results of which were published in The New England Journal of Medicine on January 30, found an almost double sustained abstinence rate after 1 year among the smokers randomly assigned to the e-cigarette group: 18.0% vs. 9.9% for nicotine-replacement products (relative risk 1.83; 95% CI: 130-2.58, p < 0.001). The study had several limitations, however, and the rate of continued e-cigarette use was fairly high. E-cigarettes may pose health risks, the severity of which are unknown, so long-term use could be problematic.
Genomic Profile Test Approved in Japan
December 27, 2018—The Ministry of Health, Labour, and Welfare (MHLW) approved the FoundationOne CDx as a comprehensive genomic profiling test for all solid tumors and as a companion diagnostic for patients with advanced cancer. Similar to the FDA approval in the United States, MHLW reimbursement coverage is expected to include MHLW-approved targeted therapies and immunotherapies therapeutic selection based on FoundationOne CDx results.
New Approval for Atezolizumab
December 6, 2018—The U.S. Food and Drug Administration (FDA) approved atezolizumab in combination with bevacizumab, paclitaxel, and carboplatin for management of metastatic nonsquamous NSCLC with no EGFR or ALK mutations in the first-line setting. Atezolizumab is also approved by the FDA for treatment of patients with metastatic NSCLC who experience disease progression during or following treatment with platinum-based chemotherapy, as well as for those patients who have EGFR or ALK mutations and have experienced disease progression during or after targeted therapy.
CheckMate-451 OS Endpoint Not Met
November 26, 2018—The phase III CheckMate-451 trial did not meet its primary endpoint of OS with combination nivolumab/ipilimumab vs. placebo as maintenance therapy for patients with extensive-stage SCLC with stable disease or response after first-line therapy with a platinum-based chemotherapy. Specific data are forthcoming, including data regarding the secondary endpoint of OS with single-agent nivolumab vs. placebo.
MYSTIC Fails to Meet Improved OS Endpoint
November 16, 2018—Phase III OS results were announced for MYSTIC, a randomized, open-label, multicenter, international trial of durvalumab monotherapy vs. durvalumab plus tremelimumab, an anti–CTLA-4 antibody, vs. platinum-based chemotherapy in treatment-naive patients with metastatic NSCLC. In the primary analysis of patients with PD-L1 expression on 25% or more of their cancer cells (as determined by the VENTANA PD-L1 Sp263 Assay), neither durvalumab alone nor its combination with tremelimumab significantly improved survival compared with chemotherapy. A hazard ratio of 0.76 (97.54% CI: 0.564-1.019; nominal p = 0.036) was observed for durvalumab alone; the combination’s HR was 0.85 (98.77% CI: 0.611-1.173; nominal p = 0.202).
Lorlatinib Approved for Second- or Third-Line Management of ALK-positive Metastatic NSCLC
November 2, 2018—The U.S. Food and Drug Administration granted accelerated approval to lorlatinib for patients with, ALK (+) metastatic or recurrent NSCLC with disease progression on crizotinib and at least one other ALK inhibitor or on alectinib or ceritinib as first ALK inhibitor therapy for metastatic or recurrent disease.
The accelerated approval was based on data from a nonrandomized, dose-ranging multicohort, multicenter study evaluating a subgroup of 215 patients with ALK-positive metastatic NSCLC who received prior treatment with one or more ALK kinase inhibitors (Study B7461001; NCT01970865). The major efficacy measures were overall response rate (ORR) and intracranial ORR, according to RECIST 1.1, as assessed by an independent central review committee.
The ORR was 48% (95% CI: 42-55), and the estimated median response duration was 12.5 months (95% CI: 8.4-23.7. Response rates were 4% for complete and 44% for partial responses. Of 89 patients with measurable CNS lesions (according to RECIST 1.1), the intracranial ORR was 60% (95% CI: 49-70), with 21% complete and 38% partial responses. The estimated median response duration was 19.5 months for those with measurable CNS lesions (95% CI: 12.4-not reached).
The most common adverse reactions (incidence ≥ 20%) were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea.
Pembrolizumab/Carboplatin Plus Paclitaxel or Nab-Paclitaxel Approved for First-Line Treatment of Metastatic Squamous NSCLC
October 30, 2018—The U.S. Food and Drug Administration (FDA) approved pembrolizumab, an anti–PD-1 agent, in combination with carboplatin and either paclitaxel or nab-paclitaxel for the first-line treatment of patients with metastatic squamous NSCLC. The approval was based on the results of the KEYNOTE-407 trial, a pivotal phase III trial in which patients who received pembrolizumab in combination with carboplatin and either paclitaxel or nab-paclitaxel experienced significantly improved overall survival, regardless of PD-L1 expression status. Risk of death was reduced by 36% for patients receiving the pembrolizumab/ chemotherapy combination compared with chemotherapy alone (HR = 0.64; 95% CI: 0.49-0.85; p = 0.0017). This is the first approval for an anti–PD-1 regimen for this indication regardless of PD-L1 expression status.
Dacomitinib Approved as EGFR TKI
September 27, 2018—The U.S. Food and Drug Administration (FDA) approved dacomitinib for the first-line treatment of patients with metastatic NSCLC who have sensitizing EGFR mutations.
Approval was based on the ARCHER 1050 trial, which compared the safety and efficacy of dacomitinib to gefitinib in 452 patients with unresectable, metastatic NSCLC. Patients were required to have no prior therapy for metastatic disease or recurrent disease with a minimum of 12 months disease-free after completion of systemic non-EGFR TKI-containing therapy; an ECOG PS of 0 or 1; and EGFR exon 19 deletion or exon 21 L858R substitution mutations. Patients were randomly assigned to receive either 45 mg of dacomitinib orally once daily or 250 mg of gefitinib orally once daily until disease progression or unacceptable toxicity.
The trial showed that dacomitinib improved OS over gefitinib (34.1 vs. 26.8 months, p = 0.0438; HR 0.76, 95% CI [0.582-0.993]). For ARCHER 1050 details and for a more robust discussion of EGFR TKIs, read the article by Edgardo S. Santos Castillero, MD.
RET Inhibitor Wins Breakthrough Therapy Designation
September 5, 2018—The U.S. Food and Drug Administration n (FDA has granted LOXO-292, an investigational new agent, Breakthrough Therapy Designation for treatment of patients with RET-positive NSCLC who require systemic therapy and have experienced disease progression following treatment with a platinum-based chemotherapy and an anti–PD-1/PD-L1 therapy.
The designation was based on the phase I/II LIBRETTO-001 trial, an open-label, multi-center trial, which will be conducted in two parts: phase I (dose escalation) and phase II (dose expansion). The trial is currently enrolling patients. Patients are eligible if they have RET-fusion–positive NSCLC that has progressed on or if they have proven intolerant to available standard therapies.
New Standard of Care for First-line Management of EGFR mutation-positive NSCLC
August 21, 2018—The Japanese Ministry of Health, Labour, and Welfare approved osimertinib for first-line treatment of patients with inoperable or recurrent EGFR mutation-positive NSCLC. Approval was based on superior progression-free survival for osimertinib (18.9 months) compared with gefitinib or erlotinib (10.2 months), which was consistent across all subgroups, as found in the FLAURA trial. Osimertinib was also generally well tolerated, with grade 3 or higher adverse events occurring in 34% of patients (vs. 45% for gefitinib or erlotinib).
Japan is the 40th country to approve osimertinib for this indication.
Alectinib Approved for ALK-Positive NSCLC in China
August 20, 2018—The China National Drug Administration granted marketing authorization for alectinib as monotherapy for patients ALK-positive advanced NSCLC. This authorization follows on the heels of US Food and Drug Administration and European Medicines Agency approvals. Authorization was based on the phase III ALEX and ALESIA studies, as well as on two phase II studies assessing alectinib for treatment of patients with disease progression on or intolerance to crizotinib. Updated ALEX results were presented June 2018 at the American Society of Clinical Oncology meeting and showed that PFS more than tripled for patients who received alectinib vs. crizotinib (34.8 months vs. 10.9 months, respectively). Specifically regarding Asian patients with ALK-positive NSCLC, ALESIA found that alectinib reduced the risk of progression or death compared with crizotinib; this data will be submitted to the CDNA to complete a post-approval agreement. Results of ALESIA will be presented at an upcoming meeting.
Nivolumab Wins First Approval for Large Group of SCLC Patients
August 17, 2018—Nivolumab was granted approval by the US Food and Drug Administration for patients with metastatic SCLC whose cancer has progressed after platinum-based chemotherapy and at least one other line of therapy. This is the first approved therapy for this indication. Because this accelerated approval was based on data from the phase I/II CheckMate-032 for overall response rate and duration of response only, further confirmatory data may be required.
In CheckMate-032 109 patients received nivolumab after platinum-based chemotherapy and at least one other prior line of therapy. Of these, 13 responded (12%), with one complete response. In a separate analysis of 245 patients with SCLC and disease progression after chemotherapy, 45% had serious adverse reactions to nivolumab, the most common being fatigue, decreased appetite, musculoskeletal pain, dyspnea, nausea, diarrhea, constipation, and cough.
Lurbinectedin Receives Orphan Drug Designation
August 3, 2018—The U.S. Food and Drug Administration (FDA) has granted Orphan Drug designation to lurbinectedin for the treatment of SCLC. Lurbinectedin (PM1183) is an investigational drug that inhibits RNA polymerase II, which is essential for transcription-addicted tumors. It is being investigated in the salvage setting for patients whose disease has progressed after initial treatment.
Europe Closes Gap to Approval of Anti–PD-1, Chemo Combination
July 30, 2018—The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion regarding approval of pembrolizumab, an anti–PD-1 therapy, in combination with pemetrexed and platinum chemotherapy (cisplatin or carboplatin) in the first-line setting for patients with metastatic nonsquamous NSCLC who do not harbor EGFR or ALK mutations, regardless of PD-L1 expression.
If approved, this would mark the first approval in Europe for anti–PD-1 therapy in combination with chemotherapy. Approval decisions are being based on OS and PFS data from KEYNOTE-189.
FDA Grants Priority Review for sBLA for Pembrolizumab
July 2, 2018—The U.S. Food and Drug Administration (FDA) granted a priority review for a supplemental biologics license application (sBLA) for pembrolizumab. The application is based on based on results of the phase III KEYNOTE-189 trial and seeks approval for pembrolizumab in combination with pemetrexed and platinum chemotherapy (carboplatin or cisplatin) as a first-line treatment for patients with metastatic NSCLC, regardless of PD-L1 expression. The FDA has set a Prescription Drug User Fee Act date of September 23, 2018.
CNDA Approves Nivolumab, China’s First PD-1 Inhibitor
June 15, 2018—the China National Drug Administration (CNDA) approved nivolumab injection for the treatment of locally advanced or metastatic NSCLC after prior platinum-based chemotherapy for patients without EGFR or ALK tumor mutations. This is China’s first and only PD-1 inhibitor. Approval was based on data from the phase III CheckMate-078 trial, in which 90% of the patients enrolled were Chinese.
ALEX Study Leads to Health Canada’s Approval of Alectinib
June 13, 2018—Health Canada approved alectinib as a monotherapy for the first-line treatment of patients with ALK-positive locally advanced (not amenable to curative therapy) or metastatic NSCLC. The approval was based on results from the phase III ALEX study, which demonstrated a reduced risk of disease progression or death by more than half (53%) with alectinib versus crizotinib. ALEX data also showed that alectinib reduced the risk of metastasis to the brain or CNS by 84% compared with crizotinib.
Medicare Approves Liquid Biopsy for NSCLC
June 12, 2018—The Guardant360® assay, a liquid biopsy by Guardant Health, Inc., has been approved for all fee-for-service Medicare patients with metastatic NSCLC who meet certain criteria. Approval was based on a recent study by Odegaard et al. of 10,593 patients with advanced solid tumors that showed high feasibility (> 99.6%) and clinical sensitivity (85.9%), with high potential actionability (72% with treatment or trial recommendations). This was especially true for patients with NSCLC; 34.5% of patient samples contained a directly targetable standard-of-care biomarker.
European Commission Grants Marketing Authorization for Osimertinib
June 8, 2018—The European Commission granted marketing authorization in early June 2018 for osimertinib as monotherapy for the first-line treatment of patients with locally-advanced or metastatic NSCLC with activating EGFR mutations. The approval is based on results from the phase III FLAURA trial.
The approval follows the positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency.
Crizotinib Receives Breakthrough Therapy Designation
May 29, 2018—A breakthrough therapy designation was granted to crizotinib, a kinase inhibitor, by the FDA for the treatment of patients with metastatic NSCLC with MET exon 14 alterations who experience disease progression after receiving platinum-based chemotherapy. Crizotinib is currently approved by the FDA for the treatment of patients with ALK- or ROS1-positive metastatic NSCLC.
Medtronic plc and Royal Philips Jointly Developing LungGPS™ Platform
January 30, 2018—Medtronic plc and Royal Philips are jointly developing and marketing the LungGPS™ Patient Management Platform. The LungGPS platform is designed to make it easier for clinicians to identify and manage patients with incidental pulmonary nodules within disparate hospital information systems.
The platform uses Natural Language Processing, a type of artificial intelligence technology that quickly searches and analyzes data contained within various medical reports and highlights relevant information for further review and follow up; it also uses Philips’ Cancer Screening Solution, a software system that automates routine administrative tasks and standardizes clinical workflows for optimized efficiency and patient care.