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10 pages, 958 KiB

Open AccessArticle

Prognostic Factors for Patients with Small-Cell Lung Cancer Treated with Chemoimmunotherapy: A Retrospective Multicenter Study

by Takashi Hatori, Takeshi Numata, Toshihiro Shiozawa, Manato Taguchi, Hirofumi Sakurai, Tomohiro Tamura, Jun Kanazawa, Hiroaki Tachi, Kyoko Kondo, Kunihiko Miyazaki, Norihiro Kikuchi, Koichi Kurishima, Hiroaki Satoh and Nobuyuki Hizawa

Curr. Oncol. 2024, 31(11), 6502-6511; https://doi.org/10.3390/curroncol31110482 - 23 Oct 2024

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Abstract

Background: This study aimed to investigate prognostic factors for predicting the survival of patients with extensive-disease-stage small-cell lung cancer treated with chemoimmunotherapy. Methods: Patients were classified according to overall survival (OS): favorable corresponded to an OS ≥ 24 months, moderate corresponded to an [...] Read more.

Background: This study aimed to investigate prognostic factors for predicting the survival of patients with extensive-disease-stage small-cell lung cancer treated with chemoimmunotherapy. Methods: Patients were classified according to overall survival (OS): favorable corresponded to an OS ≥ 24 months, moderate corresponded to an OS of 6–24 months, and poor corresponded to an OS < 6 months. Multivariate Cox regression analyses were used to evaluate prognostic factors. Results: Of 130 patients, the proportions of performance status decline and liver metastasis were significantly higher in the poor-prognosis group. With regard to the laboratory findings, neutrophil/lymphocyte ratios and albumin levels differed significantly among the groups. Multivariate analysis showed that the independent prognostic factors for OS were liver metastasis and decreased albumin levels (<3.5 mg/dL). After classifying the patients into three groups according to the quantities of these prognostic factors, the OS differed significantly among the groups (18.3 vs. 13.5 vs. 3.8 months; p < 0.001). The incidence of immune-related adverse events (irAEs) was higher in patients without these prognostic factors than in those with both (36% vs. 5%; p = 0.01). Conclusion: Liver metastasis and decreased albumin levels are independent unfavorable prognostic factors. Patients with both prognostic factors showed unfavorable OS; however, patients without these factors may have a favorable prognosis but be at greater risk of irAEs. Full article

(This article belongs to the Special Issue Immunotherapy in Thoracic Malignancies)

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12 pages, 1201 KiB

Open AccessArticle

Durvalumab-Associated Pneumonitis in Patients with Locally Advanced Non-Small Cell Lung Cancer: A Real-World Population Study

by Chloe Ahryung Lim, Sunita Ghosh, Hali Morrison, Daniel Meyers, Igor Stukalin, Marc Kerba, Desiree Hao and Aliyah Pabani

Curr. Oncol. 2023, 30(12), 10396-10407; https://doi.org/10.3390/curroncol30120757 - 9 Dec 2023

Cited by 4 | Viewed by 2327

Abstract

The PACIFIC trial led to a new standard of care for patients with locally advanced lung cancer, but real-world practice has demonstrated that immune checkpoint inhibitor (ICI) pneumonitis can lead to significant clinical complications. This study aimed to examine the clinical predictors, outcomes, [...] Read more.

The PACIFIC trial led to a new standard of care for patients with locally advanced lung cancer, but real-world practice has demonstrated that immune checkpoint inhibitor (ICI) pneumonitis can lead to significant clinical complications. This study aimed to examine the clinical predictors, outcomes, and healthcare utilization data in patients who received consolidation durvalumab. Using the Alberta Immunotherapy Database, NSCLC patients who received durvalumab in Alberta, Canada, from January 2018 to December 2021 were retrospectively evaluated. We examined incidence and predictive values of severe pneumonitis, with overall survival (OS) and time-to-treatment failure (TTF) using exploratory multivariate analyses. Of 189 patients, 91% were ECOG 0–1 and 85% had a partial response from chemoradiation prior to durvalumab. Median TTF and OS were not reached; 1-year OS was 82%. An amount of 26% developed any grade of pneumonitis; 9% had ≥grade 3 pneumonitis. Male gender and a pre-existing autoimmune condition were associated with severe pneumonitis. V20 was associated with any grade of pneumonitis. Pneumonitis development was found to be an independent risk factor for worse OS (p = 0.038) and TTF (p = 0.007). Our results suggest clinical and dosimetric predictive factors of durvalumab-associated pneumonitis. These results affirm the importance of careful patient selection for safe completion of consolidation durvalumab in real-world LA-NSCLC population. Full article

(This article belongs to the Special Issue Immunotherapy in Thoracic Malignancies)

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17 pages, 968 KiB

Open AccessArticle

Effects of Acetaminophen Exposure on Outcomes of Patients Receiving Immune Checkpoint Inhibitors for Advanced Non-Small-Cell Lung Cancer: A Propensity Score-Matched Analysis

by Fabrizio Nelli, Antonella Virtuoso, Diana Giannarelli, Agnese Fabbri, Julio Rodrigo Giron Berrios, Eleonora Marrucci, Cristina Fiore and Enzo Maria Ruggeri

Curr. Oncol. 2023, 30(9), 8117-8133; https://doi.org/10.3390/curroncol30090589 - 1 Sep 2023

Cited by 3 | Viewed by 2968

Abstract

(1) Background: Several studies have investigated potential interactions between immune checkpoint inhibitors (ICIs) and commonly prescribed medications. Although acetaminophen (APAP) has not been considered susceptible to interaction with ICIs, recent research has shown that detectable plasma levels of this drug can hinder the [...] Read more.

(1) Background: Several studies have investigated potential interactions between immune checkpoint inhibitors (ICIs) and commonly prescribed medications. Although acetaminophen (APAP) has not been considered susceptible to interaction with ICIs, recent research has shown that detectable plasma levels of this drug can hinder the efficacy of PD-1/PD-L1 blockade therapies. A reliable assessment of the potential interaction between APAP and ICIs in advanced non-small cell lung cancer (NSCLC) patients would be worthwhile since it is often prescribed in this condition. We sought to evaluate the impact of the concomitant use of APAP in patients with advanced NSCLC on PD-1/PD-L1 blockade using real-world evidence. (2) Methods: This study included consecutive patients with histologically proven stage IV NSCLC who underwent first-line therapy with pembrolizumab as a single agent or in combination with platinum-based chemotherapy, or second-line therapy with pembrolizumab, nivolumab, or atezolizumab. The intensity of APAP exposure was classified as low (therapeutic intake lasting less than 24 h or a cumulative intake lower than 60 doses of 1000 mg) or high (therapeutic intake lasting more than 24 h or a total intake exceeding 60 doses of 1000 mg). The favorable outcome of anti-PD-1/PD-L1 therapies was defined by durable clinical benefit (DCB). Progression-free survival (PFS) and overall survival (OS) were relevant to our efficacy analysis. Propensity score matching (PSM) methods were applied to adjust for differences between the APAP exposure subgroups. (3) Results: Over the course of April 2018 to October 2022, 80 patients were treated with first-line pembrolizumab either as single-agent therapy or in combination with platinum-based chemotherapy. During the period from June 2015 to November 2022, 145 patients were given anti-PD-1/PD-L1 blockade therapy as second-line treatment. Subsequent efficacy analyses relied on adjusted PSM populations in both treatment settings. Multivariate testing revealed that only the level of APAP and corticosteroid intake had an independent effect on DCB in both treatment lines. Multivariate Cox regression analysis confirmed high exposure to APAP and immunosuppressive corticosteroid therapy as independent predictors of shorter PFS and OS in both treatment settings. (4) Conclusions: Our findings would strengthen the available evidence that concomitant intake of APAP blunts the efficacy of ICIs in patients with advanced NSCLC. The detrimental effects appear to depend on the cumulative dose and duration of exposure to APAP. The inherent shortcomings of the current research warrant confirmation in larger independent series. Full article

(This article belongs to the Special Issue Immunotherapy in Thoracic Malignancies)

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10 pages, 936 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Real-World Outcomes of Stage IV NSCLC with PD-L1 ≥ 50% Treated with First-Line Pembrolizumab: Uptake of Second-Line Systemic Therapy

by Rebekah Rittberg, Bonnie Leung, Aria Shokoohi, Alexandra Pender, Selina Wong, Zamzam Al-Hashami, Ying Wang and Cheryl Ho

Curr. Oncol. 2023, 30(6), 5299-5308; https://doi.org/10.3390/curroncol30060402 - 26 May 2023

Cited by 6 | Viewed by 3562

Abstract

Introduction: Platinum-based chemotherapy was compared to single-agent pembrolizumab in advanced non-small cell lung cancer (NSCLC) with PDL1 > 50% in KEYNOTE-024. In this trial, it was found that patients who received single-agent pembrolizumab had improved progression-free survival in addition to overall survival (OS). [...] Read more.

Introduction: Platinum-based chemotherapy was compared to single-agent pembrolizumab in advanced non-small cell lung cancer (NSCLC) with PDL1 > 50% in KEYNOTE-024. In this trial, it was found that patients who received single-agent pembrolizumab had improved progression-free survival in addition to overall survival (OS). Based on KEYNOTE-024, only 53% of patients treated originally with pembrolizumab received second-line anticancer systemic therapy with an OS of 26.3 months. Based on these results, the objective of this study was to characterize real-world NSCLC patients who received second-line therapy after single-agent pembrolizumab. Methods: This was a retrospective cohort study considering stage IV NSCLC patients diagnosed with BC Cancer between 2018 and 2021 with PD-L1 ≥ 50% who received first-line single agent pembrolizumab. Patient demographics, cancer history, treatment administered, and survival were collected retrospectively. Descriptive statistics were produced. OS was calculated using Kaplan–Meier curves and compared using the log rank test. A multivariate model evaluated characteristics associated with the receipt of second-line therapy. Results: A total of 718 patients were diagnosed with Stage IV NSCLC and received at least one cycle of pembrolizumab. The median duration of treatment was 4.4 months, and the follow-up duration was 16.0 months. There were 567 (79%) patients who had disease progression, of whom 21% received second-line systemic therapy. Within the subset of patients with disease progression, the median duration of treatment was 3.0 months. It would be found that patients who received second-line therapy had better baseline ECOG performance status, were younger at diagnosis, and had a longer duration of pembrolizumab. Within the full population, the OS from the treatment initiation date was 14.0 months. OS was 5.6 months in patients who did not receive additional therapy after progression and 22.2 months in patients who received subsequent therapy. Baseline ECOG performance status was associated with improved OS in multivariate analysis. Conclusion: Based on this real-world Canadian population, 21% of patients received second-line systemic therapy, despite second-line therapy being associated with prolonged survival. In this real-world population, we found that 60% fewer patients received second-line systemic therapy when compared to KEYNOTE-024. Although differences always exist when comparing a clinical and non-clinical trial population, our findings suggest undertreating stage IV NSCLC patients. Full article

(This article belongs to the Special Issue Immunotherapy in Thoracic Malignancies)

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12 pages, 1262 KiB

Open AccessArticle

Descriptive Analysis of First-Line Non-Small Cell Lung Cancer Treatment with Pembrolizumab in Tumors Expressing PD-L1 ≥ 50% in Patients Treated in Quebec’s University Teaching Hospitals (DALP-First Study)

by Ghislain Bérard, Chantal Guévremont, Nathalie Marcotte, Coleen Schroeder, Nicole Bouchard and Raghu Rajan

Curr. Oncol. 2023, 30(3), 3251-3262; https://doi.org/10.3390/curroncol30030247 - 11 Mar 2023

Cited by 1 | Viewed by 3187

Abstract

Since July 2017, pembrolizumab has been approved as a first-line treatment of metastatic non-small cell lung cancer (NSCLC) in patients with a PD-L1 score ≥ 50% in Quebec. Study objectives were to describe and assess the real-world use of pembrolizumab; report progression-free survival [...] Read more.

Since July 2017, pembrolizumab has been approved as a first-line treatment of metastatic non-small cell lung cancer (NSCLC) in patients with a PD-L1 score ≥ 50% in Quebec. Study objectives were to describe and assess the real-world use of pembrolizumab; report progression-free survival (PFS), overall survival (OS), and immune-related adverse events (IRAEs); and compare outcomes between a fixed dose (FD) and a weight-based capped dose (WCD). Medical records of patients treated in one of Quebec’s four adult university teaching hospitals who received pembrolizumab between 1 November 2017 and 31 October 2019 were reviewed and followed until 29 February 2020. Two hundred and seventy-nine patients were included. The median real-world PFS and OS were 9.4 (95% CI, 6.6 to 11.2) and 17.3 months (95% CI, 12.9 to not reached), respectively. IRAEs causing delays or treatment interruptions were seen in 34.4% of patients. Initiating treatment with a FD (49 patients) or using a WCD (230 patients) does not appear to affect PFS, OS, or the occurrence of IRAEs. The use of a WCD strategy allowed approximately CAD 5.8 million in savings during the course of our study. These findings support the effectiveness and safety of pembrolizumab in a real-world setting. The use of a WCD does not appear to have a negative impact on patient outcomes. Full article

(This article belongs to the Special Issue Immunotherapy in Thoracic Malignancies)

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Review

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18 pages, 308 KiB

Open AccessReview

Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer Under-Represented by Clinical Trials

by Daniel E. Meyers, Rebekah Rittberg, David E. Dawe and Shantanu Banerji

Curr. Oncol. 2024, 31(9), 5498-5515; https://doi.org/10.3390/curroncol31090407 - 14 Sep 2024

Viewed by 2794

Abstract

Since the initial US FDA approval of an immune checkpoint inhibitor (ICI) for the treatment of non-oncogene-driven non-small-cell lung cancer (NSCLC) nine years ago, this therapeutic strategy has been cemented as a crucial component of treatment for most of these patients. However, there [...] Read more.

Since the initial US FDA approval of an immune checkpoint inhibitor (ICI) for the treatment of non-oncogene-driven non-small-cell lung cancer (NSCLC) nine years ago, this therapeutic strategy has been cemented as a crucial component of treatment for most of these patients. However, there is a clear efficacy–effectiveness gap whereby patients in the ‘real world’ seem to have more modest clinical outcomes compared to those enrolled in landmark clinical trials. This gap may be driven by the under-representation of important patient populations, including populations defined by clinical or molecular characteristics. In this review, we summarize the data outlining the evidence of ICIs in patients with poor Eastern Cooperative Oncology Group performance status (ECOG PS), underlying autoimmune disease (AID), older age, active brain metastases (BMs), and molecular aberrations such as EGFR mutations, ALK fusions, BRAF mutations and ROS1 fusions. Full article

(This article belongs to the Special Issue Immunotherapy in Thoracic Malignancies)

24 pages, 3349 KiB

Open AccessReview

Overcoming Resistance Mechanisms to Immune Checkpoint Inhibitors: Leveraging the Anti-Tumor Immune Response

by Courtney H. Coschi and Rosalyn A. Juergens

Curr. Oncol. 2024, 31(1), 1-23; https://doi.org/10.3390/curroncol31010001 - 19 Dec 2023

Cited by 8 | Viewed by 4060

Abstract

As far back as 3000 years ago, the immune system was observed to play a role in mediating tumor regression. Since then, many strategies have been developed to leverage the anti-tumor immune response. However, while many patients respond to ICIs up front some [...] Read more.

As far back as 3000 years ago, the immune system was observed to play a role in mediating tumor regression. Since then, many strategies have been developed to leverage the anti-tumor immune response. However, while many patients respond to ICIs up front some do not, and many of those that do eventually experience tumor progression. Currently, there are several predictive biomarkers of the immune checkpoint inhibitor response; however, no one test appears to be universally predictive and their application varies by disease site. There are many ways in which cancer cells develop primary or acquired resistance to immune checkpoint inhibitors. Efforts to reverse resistance include ways to combat T cell exhaustion, reprogram the tumor microenvironment, increase the availability of tumor neo-antigens, target alternative immune checkpoints, restore a normal/healthy patient gut microbiome, oncolytic viruses and tumor vaccines. The most studied and most promising methods include combining ICIs with therapies targeting alternative immune checkpoints and restoring a normal/healthy patient gut microbiome. This review will discuss T cell-mediated immunity, how this is leveraged by modern immunotherapy to treat cancer and mechanisms of immune checkpoint inhibitor resistance, while highlighting strategies to overcome primary and secondary resistance mechanisms. Full article

(This article belongs to the Special Issue Immunotherapy in Thoracic Malignancies)

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13 pages, 802 KiB

Open AccessEditor’s ChoiceReview

Immunotherapy in Early-Stage Non-Small Cell Lung Cancer (NSCLC): Current Evidence and Perspectives

by Chiara Lazzari, Calogera Claudia Spagnolo, Giuliana Ciappina, Martina Di Pietro, Andrea Squeri, Maria Ilenia Passalacqua, Silvia Marchesi, Vanesa Gregorc and Mariacarmela Santarpia

Curr. Oncol. 2023, 30(4), 3684-3696; https://doi.org/10.3390/curroncol30040280 - 27 Mar 2023

Cited by 19 | Viewed by 7961

Abstract

Lung cancer is the leading cause of cancer deaths in the world. Surgery is the most potentially curative therapeutic option for patients with early-stage non-small cell lung cancer (NSCLC). The five-year survival for these patients remains poor and variable, depending on the stage [...] Read more.

Lung cancer is the leading cause of cancer deaths in the world. Surgery is the most potentially curative therapeutic option for patients with early-stage non-small cell lung cancer (NSCLC). The five-year survival for these patients remains poor and variable, depending on the stage of disease at diagnosis, and the risk of recurrence following tumor resection is high. During the last 20 years, there has been a modest improvement in the therapeutic strategies for resectable NSCLC. Immune checkpoint inhibitors (ICIs), alone or in combination with chemotherapy, have become the cornerstone for the treatment of metastatic NSCLC patients. Recently, their clinical development has been shifted in the neoadjuvant and adjuvant settings where they have demonstrated remarkable efficacy, leading to improved clinical outcomes. Based on the positive results from phase III trials, ICIs have become a therapeutic option in neoadjuvant and adjuvant settings. On October 2021 the Food and Drug Administration (FDA) approved atezolizumab as an adjuvant treatment following surgery and platinum-based chemotherapy for patients with NSCLC whose tumors express PD-L1 ≥ 1%. In March 2022, nivolumab in combination with platinum-doublet chemotherapy was approved for adult patients with resectable NSCLC in the neoadjuvant setting. The current review provides an updated overview of the clinical trials exploring the role of immunotherapy in patients with early-stage NSCLC, focusing on the biological rationale for their use in the perioperative setting. We will also discuss the role of potential predictive biomarkers to personalize therapy and optimize the incorporation of immunotherapy into the multimodality management of stage I-III NSCLC. Full article

(This article belongs to the Special Issue Immunotherapy in Thoracic Malignancies)

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