Tag: Lung Cancer: Non-Small Cell

FDA Lowers PD-L1 Expression Threshold for KEYTRUDA® and Expands Indication for Frontline Treatment of NSCLC

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SUMMARY: The FDA on April 11, 2019, approved KEYTRUDA® (Pembrolizumab) for the first-line treatment of patients with Stage III Non-Small Cell Lung Cancer (NSCLC) who are not candidates for surgical resection or definitive chemoradiation, as well as those with metastatic NSCLC. Patients’ tumors must have no EGFR or ALK genomic aberrations and express PD-L1 (Tumor Proportion Score-TPS of 1% or more), as determined by an FDA-approved test. 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 2019 about 228,150 new cases of lung cancer will be diagnosed and 142,670 patients will die of the disease. Lung cancer is the leading cause of cancer-related mortality in the United States. Non-Small Cell Lung Cancer (NSCLC) accounts for approximately 85% of all lung cancers. Of the three main subtypes of NSCLC, 30% are Squamous Cell Carcinomas (SCC), 40% are Adenocarcinomas and 10% are Large Cell Carcinomas.

KEYTRUDA® (Pembrolizumab) is a fully humanized, Immunoglobulin G4, anti-PD-1, monoclonal antibody, that binds to the PD-1 receptor and blocks its interaction with ligands PD-L1 and PD-L2. It thereby reverses the PD-1 pathway-mediated inhibition of the immune response and unleashes the tumor-specific effector T cells. High level of Programmed Death-Ligand 1 (PD-L1) expression is defined as membranous PD-L1 expression on at least 50% of the tumor cells, regardless of the staining intensity. It is estimated that based on observations from previous studies, approximately 25% of the patients with advanced NSCLC have a high level of PD-L1 expression, and high level of PD-L1 expression has been associated with significantly increased response rates to KEYTRUDA®. The FDA approved KEYTRUDA® for the first-line treatment of advanced NSCLC with high PD-L1 expression (Tumor Proportion Score of 50% or more), based on KEYNOTE-024 trial, as well as in combination with Pemetrexed and Carboplatin, as first-line treatment of patients with metastatic non-squamous NSCLC, based on KEYNOTE-021 study. It is also indicated for previously treated advanced NSCLC with a much lower level of PD-L1 expression such as PD-L1 Tumor Proportion Score of 1% or higher, based on KEYNOTE-010 trial.Unleashing-T-Cell-Function-with-PD-1-and-PD-L1-Antibodies

KEYNOTE-042 is a large, international, multicenter, randomized phase III trial in which 1274 patients with untreated locally advanced or metastatic NSCLC were randomly assigned to KEYTRUDA® or chemotherapy with Paclitaxel plus Carboplatin or Pemetrexed plus Carboplatin. In this study, both squamous and non-squamous cancers with PD-L1 Tumor Proportion Score (TPS) of 1% or more were included, but tumors with sensitizing Epidermal Growth Factor Receptor (EGFR) or Anaplastic Lymphoma Kinase (ALK) mutations cancers with genetic changes, that could be treated with targeted therapies such as EGFR and ALK inhibitors, were excluded. Eligible patients were randomly assigned in a 1:1 to receive either KEYTRUDA® 200 mg IV every 3 weeks for up to 35 cycles or investigator’s choice of up to 6 cycles of chemotherapy with Paclitaxel plus Carboplatin or Pemetrexed plus Carboplatin, with optional Pemetrexed maintenance for non-squamous NSCLC. Patients were divided into 3 treatment groups based on their PD-L1 Tumor Proportion Score (TPS): TPS 50% or more (N=599), TPS 20% or more (N=818), and TPS 1% or more (N=637). Each PD-L1 expression group had equal numbers of patients receiving KEYTRUDA® and chemotherapy. The Primary end points were Overall Survival (OS) in patients with TPS 50% or more, 20% or more, and 1% or more.

At a median follow up of 12.8 months, 13.7% of patients were still receiving KEYTRUDA® compared with 4.9% on Pemetrexed maintenance therapy. It was noted that KEYTRUDA® was significantly superior to chemotherapy in all PD-L1 expression subsets. In patients with a PD-L1 TPS 50% or more, the median OS with KEYTRUDA® was 20 months versus 12.2 months for chemotherapy (HR=0.69, P=0.0003), for patients with PD-L1 TPS 20% or more, the median OS was 17.7 months versus 13 months respectively (HR=0.77, P=0.002), and for those with PD-L1 TPS 1% or more, the median OS was 16.7 months versus 12.1 months respectively (HR=0.81, P = 0.0018). The Response Rates (RR) were also higher among patients who received KEYTRUDA®, with RR of 39.5% for KEYTRUDA® versus 32% for chemotherapy in patients with a TPS 50% or more, 33.4% and 28.9% respectively in patients with TPS 20% or more and 27.3% and 26.5%, respectively, among patients with TPS of 1% or more. The duration of response was also superior with KEYTRUDA® in all three PD-L1 subgroups compared to chemotherapy (20.2 months versus 8-11 months). Patients receiving KEYTRUDA® experienced fewer severe Adverse Events, compared with chemotherapy (17.8% versus 41%).

The authors concluded that this is the largest clinical trial of KEYTRUDA® as a stand-alone therapy, and is the first study with a Primary end point of OS to demonstrate superiority of KEYTRUDA® over platinum-based chemotherapy, in patients with previously untreated locally advanced/metastatic NSCLC, without sensitizing EGFR or ALK alterations and a PD-L1 TPS of 1% or more. These data confirmed the benefit of KEYTRUDA® monotherapy as a standard first-line treatment, for PD-L1-expressing locally advanced Stage III as well as metastatic NSCLC. KEYTRUDA® monotherapy is now a new treatment option for more patients with NSCLC, including those for whom combination therapy may not be appropriate. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Mok TS, Wu Y-L, Kudaba I, et al. The Lancet. Published: April 04, 2019. DOI: https://doi.org/10.1016/S0140-6736(18)32409-7

KEYTRUDA® (Pembrolizumab)

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The FDA on April 11, 2019, approved KEYTRUDA® (Pembrolizumab) for the first-line treatment of patients with Stage III Non-Small Cell Lung Cancer (NSCLC) who are not candidates for surgical resection or definitive chemoradiation, as well as those with metastatic NSCLC. Patients’ tumors must have no EGFR or ALK genomic aberrations and express PD-L1 (Tumor Proportion Score-TPS of 1% or more), as determined by an FDA-approved test. KEYTRUDA® was previously approved as a single agent for the first-line treatment of patients with metastatic NSCLC whose tumors express PD-L1 TPS of 50% or more. KEYTRUDA® is a product of Merck Inc.

Liquid Biopsy Accurate, Reliable and Rapid in Identifying Biomarker Mutations in Newly Diagnosed Advanced Lung Cancer

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SUMMARY: The American Cancer Society estimates that for 2019 about 228,150 new cases of lung cancer will be diagnosed and 142,670 patients will die of the disease. Non Small Cell Lung Cancer (NSCLC) accounts for approximately 85% of all lung cancers. Patients with newly diagnosed metastatic NSCLC are often tested for guideline-recommended genomic biomarkers which include both predictive biomarker mutations such as EGFR, ALK, ROS1, BRAF, RET, MET, ERBB2, as well as prognostic biomarker mutation such as KRAS.

The application of precision medicine with targeted therapy requires detection of molecular abnormalities in a tissue biopsy specimen. However, if testing is not done with a comprehensive assay, such as Next-Generation Sequencing and is done in successive steps one test after another, tissue sample can be depleted, with not enough tissue left for testing of all biomarkers. Following progression or recurrence, archived biopsy specimens may not be helpful, as it is important to identify additional mutations in the tumor at the time of recurrence or progression, in order to plan appropriate therapy. Further, recurrent tumors may be inaccessible for a safe biopsy procedure or the clinical condition of the patient may not permit a repeat biopsy. Additionally, the biopsy itself may be subject to sampling error due to tumor heterogeneity. Genotyping circulating cell-free tumor DNA (cfDNA) in the plasma can potentially overcome the shortcomings of repeat biopsies and tissue genotyping, allowing the detection of many more targetable gene mutations, thus resulting in better evaluation of the tumor genome landscape.

The Noninvasive versus Invasive Lung Evaluation (NILE) trial is a prospective, multicenter study conducted to demonstrate the noninferiority of comprehensive cell-free DNA (cfDNA) relative to standard-of-care traditional tissue genotyping tests, to identify guideline-recommended genomic biomarkers, in patients with metastatic NSCLC. The authors in this study enrolled 282 newly diagnosed patients at 28 North American centers, with previously untreated, nonsquamous, metastatic NSCLC undergoing standard-of-care tissue genotyping. Enrolled patients submitted a pretreatment blood sample for cfDNA analysis utilizing a CLIA-certified comprehensive 73-gene next generation sequencing panel (Guardant360®). Over 80% of the enrolled patients were white and over 50% were female.

The liquid biopsy utilizing Guardant360®, detected biomarker mutations at a rate similar to standard-of-care tissue genotyping tests, in the enrolled patients, meeting the Primary study objective. At least one of the guideline-recommended genomic biomarkers was detected in 60 patients (21.3%) using tissue-based tests and in 77 patients (27.3%) by cfDNA utilizing Guardant360® (P<0.0001). The detection rate was increased by 48% when Guardant360® was utilized for cfDNA analysis and this included those with negative, not assessed, or Quantity Not Sufficient (QNS) results in tissue. In addition, the Positive Predictive Value was 100% for cfDNA versus tissue genotyping, for FDA approved targets such as EGFR, ALK, ROS1, and BRAF mutations. There are agents already approved by the FDA to treat this patient population. The median turnaround time was significantly lower for cfDNA, compared to tissue genotyping (9 versus 15 days; P <0.0001).

The authors concluded that in this largest cfDNA study among patients with previously untreated advanced NSCLC, cfDNA successfully detected seven biomarker mutations noninvasively, significantly faster than tissue genotype testing, and was also able to rescue biomarker mutation positive patients who had non-diagnostic tissue results. They added that the findings in this study confirms similar findings from Europe and demonstrates the clinical utility of cfDNA in newly diagnosed metastatic NSCLC. Clinical utility of comprehensive cell-free DNA (cfDNA) analysis to identify genomic biomarkers in newly diagnosed metastatic non-small cell lung cancer (mNSCLC). Leighl N, Page RD, Raymond VM, et al. Presented at: AACR Annual Meeting April 2, 2019; Philadelphia, USA.

Baseline Corticosteroid Use at Start of PD-1/PD-L1 Inhibitor Therapy Negatively Affects Outcomes in NSCLC

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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. Non Small Cell Lung Cancer (NSCLC) accounts for approximately 85% of all lung cancers. Immunotherapy with PD-1 (Programmed cell Death 1) and PD-L1 (Programmed cell Death Ligand 1) inhibitors have demonstrated a clear survival benefit both as a single agent or in combination, compared with standard chemotherapy, in both treatment-naive and previously treated patients for advanced Non Small Cell Lung Cancer (NSCLC). It is now standard therapy for patients with lung cancer. Immuno-Oncology therapies unleash the T cells by blocking the Immune checkpoint proteins, thereby resulting in T cell proliferation, activation and a therapeutic response.

Patients with NSCLC often are treated with corticosteroids for a variety of reasons including fatigue, dyspnea, decreased appetite, and symptomatic brain metastases. Corticosteroids by virtue of their immunosuppressive properties can potentially effect on T-cell function and for this reason, use of these agents before the start of therapy with PD-(L)1 blockade has been a uniform exclusion criterion in clinical trials of Immune Checkpoint Blockade therapies. It is however becoming increasing clear that corticosteroids use for the management of immune-related adverse events do not seem to negatively impact outcomes. Nonetheless, there are presently no data regarding the impact of corticosteroid use at baseline, on the efficacy of Immune Checkpoint Inhibitors. In this publication, the authors evaluated the potential impact of systemic corticosteroids at the start of Immune Checkpoint Blockade, on the efficacy of PD-(L)1 inhibitors.

The authors in this study identified patients with advanced NSCLC who were treated with single-agent PD-(L)1 inhibitor (Pembrolizumab, Nivolumab, Atezolizumab, or Durvalumab) from two institutions – Memorial Sloan Kettering Cancer Center (N=455) and Gustave Roussy Cancer Center (N=185), between April 2011 to September 2017. Clinical and pharmacy records were reviewed to identify corticosteroid use at the time of beginning anti-PD-(L)1 therapy. Information on the use of corticosteroids within 30 days of the start of PD-(L)1 blockade, type of corticosteroid used, indication and route of administration were collected for the MSKCC cohort. Patient characteristics, including age, gender, histology, ECOG Performance Status, and smoking history were collected for all patients. Efficacy outcomes following treatment with PD-(L)1 inhibitors blockade was determined by local radiologists and all patients were followed up until death or data lock.

It was noted that 14% (N=90) of the 640 patients treated with single-agent PD-(L)1 inhibitor received 10 mg or more of prednisone daily at the start of the treatment with a PD-(L)1 inhibitor. The most common indications for treatment with corticosteroids were dyspnea or other respiratory symptoms (33%), fatigue (21%), and brain metastases (19%). Patient characteristics were well balanced between those who did or did not receive corticosteroids, with two exceptions – patients with poor performance status and history of brain metastases were more common in those who received corticosteroids.

In the pooled cohort of patients from both participating institutions, patients receiving baseline corticosteroids compared with patients not receiving corticosteroids experienced a lower Objective Response Rate (7% versus 18%) and worse Progression Free Survival and Overall Survival (P<0.001). The authors performed a multivariable analysis in the pooled cohort (N = 640), incorporating smoking history, performance status, history of brain metastases, and corticosteroid use (Prednisone 10 mg or more versus less than 10 mg), at the start of PD-(L)1 blockade. Prednisone use 10 mg or more was associated with worse Progression Free Survival (P=0.03) and Overall Survival (P<0.001). In the Memorial Sloan Kettering Center cohort of patients, (data unavailable for the Gustave Roussy Cancer Center cohort), patients who discontinued corticosteroids 1-30 days before starting PD-(L)1 blockade had intermediate Progression Free Survival and Overall Survival compared to those who received corticosteroids on the day of PD-(L)1 blockade initiation and those who received no corticosteroids within 30 days of the start of therapy.

The authors concluded that among patients with Non Small Cell Lung Cancer treated with PD-(L)1 blockade, baseline corticosteroid use of 10 mg or more of prednisone equivalent was associated with inferior outcomes. Clinicians should exercise caution and minimize the use, duration, and dose of corticosteroids if immunotherapy with PD-(L)1 blockade is a future consideration. Impact of Baseline Steroids on Efficacy of Programmed Cell Death-1 and Programmed Death-Ligand 1 Blockade in Patients With Non-Small-Cell Lung Cancer. Arbour KC, Mezquita L, Long N, et al. J Clin Oncol. 2018;36:2872-2878

TECENTRIQ® (Atezolizumab)

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The FDA on December 6, 2018 approved TECENTRIQ® in combination with AVASTIN® (Bevacizumab), TAXOL® (Paclitaxel), and Carboplatin for the first-line treatment of patients with metastatic non-squamous, Non-Small Cell Lung Cancer (NSq NSCLC) with no EGFR or ALK genomic tumor aberrations. TECENTRIQ® is a product of Genentech, Inc.

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

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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

LORBRENA® (Lorlatinib)

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The FDA on November 2, 2018 granted accelerated approval to LORBRENA®, for patients with Anaplastic Lymphoma Kinase (ALK)-positive metastatic Non-Small Cell Lung Cancer (NSCLC) whose disease has progressed on Crizotinib and at least one other ALK inhibitor for metastatic disease or whose disease has progressed on Alectinib or Ceritinib as the first ALK inhibitor therapy for metastatic disease. LORBRENA® is a product of Pfizer, Inc.

KEYTRUDA® (Pembrolizumab)

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The FDA on October 16, 2018 approved KEYTRUDA® in combination with Carboplatin and either Paclitaxel or nab-Paclitaxel, as first-line treatment of metastatic squamous Non-Small Cell Lung Cancer (NSCLC). KEYTRUDA® is a product of Merck & Co. Inc.

IMFINZI® after Chemoradiotherapy Significantly Improves Overall Survival in Stage III NSCLC

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IMFINZI® (Durvalumab) is a selective, high-affinity, human IgG1 monoclonal antibody, that blocks the binding of Programmed Death Ligand 1 (PD-L1) to Programmed Death 1 (PD-1) receptor and CD80, thereby unleashing the T cells to recognize and kill tumor cells. Patients with stage III Non Small Cell Lung Cancer (NSCLC) are often treated with platinum-based doublet chemotherapy with concurrent radiation and have a median Progression Free Survival (PFS) of approximately 8 months and 5 year survival of only 15%. PACIFIC trial is a randomized, double-blind, international, phase III study in which IMFINZI® as consolidation therapy was compared with placebo, in patients with stage III, locally advanced, unresectable NSCLC, that had not progressed following platinum-based chemoradiotherapy.
At a median follow up of 25.2 months, the 24-month Overall Survival rate was 66.3% in the IMFINZI® group and 55.6% in the placebo group, suggesting a significantly prolonged Overall Survival with IMFINZI® when compared with placebo and a 32% reduction in the risk of death (HR for death=0.68; P=0.0025). The Overall Survival benefit with IMFINZI®, was observed across all the prespecified subgroups.
PACIFIC trial is the first study to demonstrate a survival advantage for unresectable Stage III NSCLC, supporting this regimen as the standard of care.

IMFINZI® after Chemoradiotherapy Significantly Improves Overall Survival in Stage III NSCLC

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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. Non Small Cell Lung Cancer (NSCLC) accounts for approximately 85% of all lung cancers. Of the three main subtypes of Non Small Cell Lung Cancer (NSCLC), approximately 30% are Squamous Cell Carcinomas (SCC), 40% are Adenocarcinomas, and 10% are Large cell carcinomas.

Approximately one third of all patients with NSCLC have stage III, locally advanced disease at the time of initial presentation. Worldwide, about 500,000 patients are diagnosed with unresectable, stage III NSCLC, each year. These patients include those with locally advanced primary tumors with tumor invading the vital mediastinal organs, as well as those with involvement of locoregional mediastinal lymph nodes. These patients are often treated with platinum-based doublet chemotherapy with concurrent radiation and have a median Progression Free Survival (PFS) of approximately 8 months and 5 year survival of only 15%. There is hence a significant unmet need for this patient group, with no major treatment advances thus far.

Preclinical evidence had suggested that chemotherapy and radiotherapy may upregulate PD-L1 expression in tumor cells. IMFINZI® (Durvalumab) is a selective, high-affinity, human IgG1 monoclonal antibody, that blocks the binding of Programmed Death Ligand 1 (PD-L1) to Programmed Death 1 (PD-1) receptor and CD80, thereby unleashing the T cells to recognize and kill tumor cells. IMFINZI® showed encouraging antitumor activity in an early phase clinical study involving multiple advanced solid tumors, including stage IIIB or IV NSCLC.

PACIFIC trial is a randomized, double-blind, international, phase III study in which IMFINZI® as consolidation therapy was compared with placebo, in patients with stage III, locally advanced, unresectable NSCLC, that had not progressed following platinum-based chemoradiotherapy. Eligible patients received two or more cycles of platinum-based doublet chemotherapy concurrently with definitive radiation therapy (54-66 Gy). Following completion of concurrent chemoradiation treatment, 713 patients were randomized, of whom 709 patients in a 2:1 ratio received consolidation treatment, within 6 weeks after completion of chemoradiation, with IMFINZI® 10 mg/kg every 2 weeks (N=473) or placebo (N=236), for up to 12 months. The median age was 64 years, and the majority of patients were men (70%) and 46% had a squamous histology. The co-Primary end points were Progression Free Survival (PFS) and Overall Survival (OS). Secondary end points included 12-month and 18-month PFS rates, Objective Response Rate (ORR), Duration of Response, time to death or distant metastasis, and safety.

The authors had previously reported the results of the first preplanned interim analysis, after a median follow up of 14.5 months. The median PFS from randomization to consolidation treatment was 16.8 months with IMFINZI® versus 5.6 months with placebo (HR=0.52; P<0.001). This meant a 11.2-month improvement in PFS with IMFINZI® versus placebo, and a 48% decrease in the probability of disease progression with IMFINZI®. This improvement was consistent across all patient subgroups that were analyzed.

The authors in this publication report the results for the second Primary end point of Overall Survival. At a median follow up of 25.2 months, the 24-month Overall Survival rate was 66.3% in the IMFINZI® group and 55.6% in the placebo group, suggesting a significantly prolonged Overall Survival with IMFINZI® when compared with placebo and a 32% reduction in the risk of death (HR for death=0.68; P=0.0025). The Overall Survival benefit with IMFINZI®, was observed across all the prespecified subgroups. In this updated analysis, the PFS was similar to those previously reported, with a median duration of 17.2 months in the IMFINZI® group and 5.6 months in the placebo group (HR=0.51). The median time to death or distant metastasis was 28.3 months in the IMFINZI® group and 16.2 months in the placebo group (HR=0.53). Approximately 30% of the patients in the IMFINZI® group and 26% of those in the placebo group had grade 3 or 4 adverse events of any cause, and 15% and 10% of the patients respectively, discontinued the trial regimen because of adverse events.

The authors concluded that in this updated analysis of the PACIFIC trial, the Primary end point of Overall Survival was significantly longer with IMFINZI® than with placebo, among patients with unresectable stage III NSCLC, in all the prespecified subgroups. The updated results for Secondary end points, including the time to death or distant metastasis, the incidence of new lesions, and the Objective Response Rate, were similar to those that were previously reported. The authors commented that PACIFIC trial is the first study to demonstrate a survival advantage for unresectable Stage III NSCLC, supporting this regimen as the standard of care. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. Antonia SJ, Villegas A, Daniel D, et al. [published online ahead of print September 25, 2018]. N Eng J Med. doi: 10.1056/NEJMoa1809697.