The International Association for the Study of Lung Cancer Issues Statement on Lung Cancer Screening CALL TO ACTION

SUMMARY: Lung cancer is the second most common cancer in both men and women and accounts for about 14% of all new cancers and 27% of all cancer deaths. The American Cancer Society estimates that for 2018 about 234,030 new cases of lung cancer will be diagnosed and over 154,050 patients will die of the disease. Lung cancer is the leading cause of cancer related mortality in the United States. Lung cancer is a growing global epidemic with 1.6 million deaths annually. Over 60% of individuals present with advanced disease at the time of diagnosis and this can result in poor outcomes. Early detection can however lead to lowered mortality. Implementing a validated tool to reliably detect early stage, curable lung cancer has been a priority of the International Association for the Study of Lung Cancer (IASLC), in its mission to conquer thoracic cancers worldwide.

The IASLC on October 25, 2018 issued a statement on lung cancer screening with Low-Dose Computed Tomography (LDCT), based on results from the Dutch-Belgian NELSON lung cancer screening trial presented at the IASLC 19th World Conference on Lung Cancer (WCLC) in Toronto, Canada. The IASLC is the only global organization dedicated solely to the study of lung cancer and other thoracic malignancies and includes more than 7,500 lung cancer specialists across all disciplines in over 100 countries.

EVIDENCE:

The National Lung Cancer Screening Trial (NLST) demonstrated that annual lung cancer screening with Low-Dose CT (LDCT) reduced lung cancer mortality by 20% and overall mortality by 7% compared with controls. Based on the NLST results, NCCN issued guidelines recommending LDCT in 2011, USPSTF (United States Preventive Services Task Force) recommended lung cancer screening with LDCT in high risk patients in 2013 and Low-Dose CT screening was approved in the United States for those at high risk (between the ages of 55 and 77 and a smoking history of 30 pack-years or more and not have quit within the past 15 years).

The Dutch-Belgian Lung Cancer Screening Trial (NELSON) is Europe’s largest lung cancer screening trial and enrolled 15,792 individuals at high risk for lung cancer. Data from this study was presented at the World Conference on Lung Cancer this year which decisively confirmed that annual lung cancer screening with Low-Dose CT in high-risk patients ((age 50-74 years, more than 10 cigarettes/day for more than 30 years or more than 15 cigarettes/day for more than 25 years), reduced lung cancer deaths by 26% in men and up to 61% in women.

RECOMMENDATIONS:

With two trials from the United States and Europe demonstrating significant mortality reduction in high risk, tobacco-exposed populations, IASLC emphasizes that early detection must be routinely provided along with best-practice smoking cessation, to enable optimal health outcomes in the setting of individuals who continue to consume tobacco products. Acknowledging that for implementation of Low-Dose CT screening worldwide, each national health service has the authority to decide its own course of action, IASLC has urged its members and others around the world to implement screening programs that incorporate a multidisciplinary group of experts and use best practice in screening care, with focus on the following:

Identification of high-risk individuals

Acquisition of consistent high-quality images (from Low-Dose CT) and incorporation of radiologic guidelines, including definitions for positive versus negative results

Use of defined clinical workup for indeterminate nodules and for pathology reporting of nodules

Incorporation of a defined process for surgical or other diagnostic interventions of suspicious nodules

Integration of smoking cessation into lung cancer CT screening programs

It was concluded that based on the data from these two large, well designed US and European randomized trials, the WCLC committee’s screening experts came to an unanimous consensus that now is the time for international leaders, governments, health care systems and other stakeholders to implement global lung cancer screening programs, as they do for breast cancer (mammography) and colon cancer (colonoscopy), which save the thousands of lives. https://www.iaslc.org/news/iaslc-issues-statement-lung-cancer-screening-low-dose-computed-tomography

FDA Approves VENCLEXTA® for Elderly Patients with AML

SUMMARY: The FDA on November 21, 2018 granted accelerated approval to VENCLEXTA® (Venetoclax) in combination with Azacitidine or Decitabine or low-dose Cytarabine for the treatment of newly diagnosed Acute Myeloid Leukemia (AML) in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. The American Cancer Society estimates that in 2018, 19,520 new cases of Acute Myeloid Leukemia (AML) will be diagnosed in the United States and 10,670 patients will die of the disease. AML can be considered as a group of heterogeneous diseases with different clinical behavior and outcomes. A significant percentage of patients with newly diagnosed AML are not candidates for intensive chemotherapy. Even with the best available therapies, the 5 year Overall Survival in patients 65 years of age or older is less than 5%.

The pro-survival (anti-apoptotic) protein BCL2 is over expressed by AML cells and regulates clonal selection and cell survival. A new class of anticancer agents known as BH3-mimetic drugs mimic the activity of the physiologic antagonists of BCL2 and related proteins and promote apoptosis (programmed cell death). VENCLEXTA® is a second generation, oral, selective, small molecule inhibitor of BCL2 and restores the apoptotic processes in tumor cells.

The present FDA approval was based on two open-label non-randomized clinical trials in patients with newly diagnosed AML who were 75 years of age or older or had comorbidities that precluded the use of intensive induction chemotherapy. Efficacy was established based on the rate of Complete Remission (CR) and CR duration.

The M14-358 study is an open-label, phase Ib dose escalation and expansion study which evaluated the safety and efficacy of VENCLEXTA® in combination with HypoMethylating Agents, Azacitidine or Decitabine. This study included a subpopulation of 80 patients who received VENCLEXTA® (daily ramp-up to a final dose of 400 mg once daily) in combination with a hypomethylating agent, either Azacitidine (N=67) or Decitabine (N=13). Patients were hospitalized for monitoring during the ramp-up and received prophylaxis for Tumor Lysis Syndrome. Azacitidine was administered at 75 mg/m2 SC or IV on days 1-7 of each 28-day cycle and Decitabine was administered at 20 mg/m2 IV on days 1-5 of each 28-day cycle. Treatment was continued until disease progression or unacceptable toxicity. Majority of patients in each treatment group had an ECOG performance status of 0 or 1. In the Azacitidine group, 64% of patients had intermediate cytogenetic risk and 34% had poor cytogenetic risk whereas this was 38% and 62%, respectively in the Decitabine group.

The median follow up was 7.9 months for the Azacitidine group and 11 months for the Decitabine group. The Complete Response rate was 37% in the Azacitidine group with a median observed time in remission of 5.5 months. The rates of CR with partial hematologic recovery were 24%. In combination with Decitabine, the CR rate was 54%, with a median observed time in remission of 4.7 months. The CR with partial hematologic recovery was 7.7%.

The M14-387 study is an open-label, phase Ib/II dose escalation and expansion study which evaluated the safety and efficacy of VENCLEXTA® in combination with Low Dose Ara-C (Cytarabine). This study included a subpopulation of 61 AML patients who received VENCLEXTA® plus low-dose Cytarabine. Included patients had newly diagnosed AML, and some patients had previous exposure to a HypoMethylating Agent for an antecedent hematologic disorder. Patients received VENCLEXTA® (daily ramp-up to a final dose of 600 mg orally once daily). Patients were hospitalized for monitoring during the ramp-up and received prophylaxis for Tumor Lysis Syndrome. Cytarabine was given at 20 mg/m2 SC on days 1-10 of each 28-day cycle. Treatment was continued until disease progression or unacceptable toxicity.

At a median follow-up of 6.5 months, the CR rate was 21%, with a median observed time in remission of 6 months. The rate of CR with partial hematologic recovery was 21%. The most common adverse reactions to VENCLEXTA® in combination with Azacitidine, Decitabine or low-dose Cytarabine were fever, nausea, vomiting, diarrhea, fatigue, cytopenias, myalgias, dyspnea, peripheral edema and hypotension.

This FDA approval marks a significant advance for patients with Acute Myeloid Leukemia, who are unable to tolerate standard intensive induction chemotherapy. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm626499.htm

XOSPATA® (Gilteritinib)

The FDA on November 28, 2018 approved XOSPATA® for treatment of adult patients who have relapsed or refractory Acute Myeloid Leukemia (AML) with a FLT3 mutation as detected by an FDA-approved test. XOSPATA® is a product of Astellas Pharma US Inc.

TRUXIMA® (Rituximab-abbs)

The FDA on November 28, 2018 approved TRUXIMA® as the first biosimilar to RITUXAN® (Rituximab) for patients with CD20-positive, B-cell non-Hodgkin’s lymphoma (NHL), to be used as a single agent or in combination with chemotherapy. TRUXIMA® is a product of Celltrion Inc.

VITRAKVI® (Larotrectinib)

The FDA on November 26, 2018 granted accelerated approval to VITRAKVI® for adult and pediatric patients with solid tumors that have a Neurotrophic Receptor Tyrosine Kinase (NTRK) gene fusion without a known acquired resistance mutation, that are either metastatic or where surgical resection is likely to result in severe morbidity, and who have no satisfactory alternative treatments or whose cancer has progressed following treatment. VITRAKVI® is a product of Loxo Oncology Inc. and Bayer.

VENCLEXTA® (Venetoclax)

The FDA on November 21, 2018 granted accelerated approval to VENCLEXTA® in combination with Azacitidine or Decitabine or low-dose Cytarabine for the treatment of newly-diagnosed Acute Myeloid Leukemia (AML) in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. VENCLEXTA® is a product of AbbVie Inc. and Genentech Inc.

DAURISMO® (Glasdegib)

The FDA on November 21, 2018 approved DAURISMO® in combination with Low-Dose Cytarabine (LDAC), for newly-diagnosed Acute Myeloid Leukemia (AML) in patients who are 75 years old or older or who have comorbidities that preclude intensive induction chemotherapy. DAURISMO® is a product of Pfizer Labs.

GAMIFANT® (Emapalumab)

The FDA on November 20, 2018 approved GAMIFANT®, a monoclonal antibody that binds and neutralizes Interferon Gamma, for adult and pediatric (newborn and older) patients with primary Hemophagocytic Lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy. GAMIFANT® is a product of Novimmune SA.