The Evolving Role of Maintenance Therapy Using Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR TKIs) in the Management of Advanced Non-Small-Cell Lung Cancer

A video abstract by the authors of this paper is available. video-abstract5127.mo

Safety and Efficacy of Pemetrexed in Maintenance Therapy of Non-Small Cell Lung Cancer

Lung cancer incidence continues to rise and is the number one cause of cancer death in both men and women worldwide with projected 221,130 new cases and 156,940 deaths in the United States in 2011.1 Non-small cell lung cancer (NSCLC) represents more than 85% of the cases with most patients having either locally advanced or metastatic disease at the time of initial diagnosis, and approximately 60%–70% of them have an adenocarcinoma histologic subtype. In the last three years, we have seen several advances in the management of NSCLC, with several factors playing an important role in the treatment decision making process. Maintenance therapy has been added to the algorithm of NSCLC management and Pemetrexed has been studied as single agent or in combination in this setting with recent studies showing safety and improved progression free survival (PFS) and/or overall survival (OS), still the disease for the most part has a dismal outcome. More research work needs to be done to identify which patients truly benefit from these approaches, and to whom we should offer maintenance or switch maintenance vs. close observation

The Effectiveness of Maintenance Pharmacotherapies for Non-Small Cell Lung Cancer

Although current recommendations for the treatment of advanced non-small cell lung cancer (NSCLC) include a maximum of six cycles of platinum-based combination therapy as a first-line approach, most patients experience progression within 3–4 months. Therefore, a new treatment strategy, maintenance therapy, has been proposed, and several large randomized prospective controlled trials have shown benefits with maintenance therapy. Maintenance therapy can be classified as either continuation maintenance, which is defined as a prolongation of a part of the first-line chemotherapy or molecularly targeted agent until progression, or switch-maintenance, which is defined as the administration of a different cytotoxic chemotherapy or molecularly targeted agent immediately after induction therapy. In this article, recent results from large randomized phase III trials regarding maintenance therapy are reviewed in order to evaluate the role of maintenance therapy in NSCLC

1386pdimpower150 clinical safety tolerability and immune related adverse events in a phase iii study of atezolizumab atezo chemotherapy chemo bevacizumab bev vs chemo bev in 1l nonsquamous nsclc

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A Single Center Retrospective Study of the Impact of COVID-19 Infection on Immune-related Adverse Events in Cancer Patients Receiving Immune Checkpoint Inhibitors

Immune checkpoint inhibitors (ICIs) can cause a variety of immune-related adverse events (irAEs). The coronavirus disease 2019 (COVID-19) is associated with increased amounts of pro-inflammatory cytokines, which may affect the outcome of irAEs. Data are limited regarding the impact of COVID-19 on irAEs in ICI-treated cancer patients. Hence, in this study, we retrospectively analyzed ICI-treated adult patients with malignant solid tumors at a single institution between August 2020 and August 2021. Patients who had the most recent ICI treatment over 1-month before or after the positive COVID-19 test were excluded from the study. For the COVID-19 positive group, only the irAEs that developed after COVID-19 infection were considered as events. A total of 579 patients were included in our study, with 46 (7.9%) in the COVID-19 positive group and 533 (92.1%) in the COVID-19 negative group. The baseline characteristics of patients in the 2 groups were similar. With a median follow-up of 331 days (range: 21-2226), we noticed a nonsignificant higher incidence of all-grade irAEs in the COVID-19 positive group (30.4% vs. 19.9%, P=0.18). The incidence of grade 3 and 4 irAEs was significantly higher in the COVID-19 positive group (10.9% vs. 3.2%, P=0.02). Multivariate analysis confirmed the association between COVID-19 infection and increased risk of severe irAE development (odds ratio: 1.08, 95% confidence interval: 1.02-1.14, P=0.01). Our study suggested that COVID-19 may pose a risk of severe irAEs in cancer patients receiving ICIs. Close monitoring and possibly delaying ICI administration could be considered when cancer patients are infected with COVID-19

First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer.

Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive NSCLC. We randomly assigned, in a 1:1 ratio, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab (administered intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks) or platinum-based chemotherapy (administered once every 3 weeks for up to six cycles). Patients receiving chemotherapy could cross over to receive nivolumab at the time of disease progression. The primary end point was progression-free survival, as assessed by means of blinded independent central review, among patients with a PD-L1 expression level of 5% or more. Among the 423 patients with a PD-L1 expression level of 5% or more, the median progression-free survival was 4.2 months with nivolumab versus 5.9 months with chemotherapy (hazard ratio for disease progression or death, 1.15; 95% confidence interval [CI], 0.91 to 1.45; P=0.25), and the median overall survival was 14.4 months versus 13.2 months (hazard ratio for death, 1.02; 95% CI, 0.80 to 1.30). A total of 128 of 212 patients (60%) in the chemotherapy group received nivolumab as subsequent therapy. Treatment-related adverse events of any grade occurred in 71% of the patients who received nivolumab and in 92% of those who received chemotherapy. Treatment-related adverse events of grade 3 or 4 occurred in 18% of the patients who received nivolumab and in 51% of those who received chemotherapy. Nivolumab was not associated with significantly longer progression-free survival than chemotherapy among patients with previously untreated stage IV or recurrent NSCLC with a PD-L1 expression level of 5% or more. Overall survival was similar between groups. Nivolumab had a favorable safety profile, as compared with chemotherapy, with no new or unexpected safety signals. (Funded by Bristol-Myers Squibb and others; CheckMate 026 ClinicalTrials.gov number, NCT02041533 .)

Atezolizumab in Combination With Carboplatin and Nab-Paclitaxel in Advanced Squamous NSCLC (IMpower131): Results From a Randomized Phase III Trial

Introduction: Cytotoxic agents have immunomodulatory effects, providing a rationale for combining atezolizumab (anti-programmed death-ligand 1 [anti–PD-L1]) with chemotherapy. The randomized phase III IMpower131 study (NCT02367794) evaluated atezolizumab with platinum-based chemotherapy in stage IV squamous NSCLC. Methods: A total of 1021 patients were randomized 1:1:1 to receive atezolizumabþcarboplatinþpaclitaxel (AþCP) (n ¼ 338), atezolizumabþcarboplatinþnab-paclitaxel (AþCnP) (n ¼ 343), or carboplatinþnab-paclitaxel (CnP) (n ¼ 340) for four or six 21-day cycles; patients randomized to the AþCP or AþCnP arms received atezolizumab maintenance therapy until progressive disease or loss of clinical benefit. The coprimary end points were investigatorassessed progression-free survival (PFS) and overall survival (OS) in the intention-to-treat (ITT) population. The secondary end points included PFS and OS in PD-L1 subgroups and safety. The primary PFS (January 22, 2018) and final OS (October 3, 2018) for AþCnP versus CnP are reported. Results: PFS improvement with AþCnP versus CnP was seen in the ITT population (median, 6.3 versus 5.6 mo; hazard ratio [HR] ¼ 0.71, 95% confidence interval [CI]: 0.60–0.85; p ¼ 0.0001). Median OS in the ITT population was 14.2 and 13.5 months in the AþCnP and CnP arms (HR ¼ 0.88, 95% CI: 0.73–1.05; p ¼ 0.16), not reaching statistical significance. OS improvement with AþCnP versus CnP was observed in the PD-L1–high subgroup (HR ¼ 0.48, 95% CI: 0.29–0.81), despite not being formally tested. Treatment-related grade 3 and 4 adverse events and serious adverse events occurred in 68.0% and 47.9% (AþCnP) and 57.5% and 28.7% (CnP) of patients, respectively. Conclusions: Adding atezolizumab to platinum-based chemotherapy significantly improved PFS in patients with first-line squamous NSCLC; OS was similar between the arms

Feasibility assessment of patient reporting of symptomatic adverse events in multicenter cancer clinical trials

IMPORTANCE: In cancer clinical trials, symptomatic adverse events (AEs), such as nausea, are reported by investigators rather than by patients. There is increasing interest to collect symptomatic AE data via patient-reported outcome (PRO) questionnaires, but it is unclear whether it is feasible to implement this approach in multicenter trials. OBJECTIVE: To examine whether patients are willing and able to report their symptomatic AEs in multicenter trials. DESIGN, SETTING, AND PARTICIPANTS: A total of 361 consecutive patients enrolled in any 1 of 9 US multicenter cancer treatment trials were invited to self-report 13 common symptomatic AEs using a PRO adaptation of the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) via tablet computers at 5 successive clinic visits. Patient adherence was tracked with reasons for missed self-reports. Agreement with clinician AE reports was analyzed with weighted κ statistics. Patient and investigator perspectives were elicited by survey. The study was conducted from March 15, 2007, to August 11, 2011. Data analysis was performed from August 9, 2013, to March 21, 2014. RESULTS: Of the 361 patients invited to participate, 285 individuals enrolled, with a median age of 57 years (range, 24-88), 202 (74.3%) female, 241 (85.5%) white, 73 (26.8%) with a high school education or less, and 176 (64.7%) who reported regular internet use (denominators varied owing to missing data). Across all patients and trials, there were 1280 visits during which patients had an opportunity to self-report (ie, patients were alive and enrolled in a treatment trial at the time of the visit). Self-reports were completed at 1202 visits (93.9% overall adherence). Adherence was highest at baseline and declined over time (visit 1, 100%; visit 2, 96%; visit 3, 95%; visit 4, 91%; and visit 5, 85%). Reasons for missing PROs included institutional errors in 27 of 48 (56.3%) of the cases (eg, staff forgetting to bring computers to patients at visits), patients feeling “too ill” in 8 (16.7%), patient refusal in 8 (16.7%), and internet connectivity problems in 5 (10.4%). Patient-investigator CTCAE agreement was moderate or worse for most symptoms (most κ < 0.05), with investigators reporting fewer AEs than patients across symptoms. Most patients believed that the system was easy to use (234 [93.2%]) and useful (230 [93.1%]), and investigators thought that the patient-reported AEs were useful (133 [94.3%]) and accurate (119 [83.2%]). CONCLUSIONS AND RELEVANCE: Participants in multicenter cancer trials are willing and able to report their own symptomatic AEs at most clinic visits and report more AEs than investigators. This approach may improve the precision of AE reporting in cancer trials