scholarly journals Making Checkpoint Inhibitors Part of Treatment of Patients With Locally Advanced Lung Cancers: The Time Is Now

2020 ◽  
pp. e159-e170
Author(s):  
Mark G. Kris ◽  
Corinne Faivre-Finn ◽  
Tiana Kordbacheh ◽  
Jamie Chaft ◽  
Jia Luo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Local Therapy ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Concurrent Chemoradiation ◽  
Stage Iii ◽  
Advanced Lung Cancer ◽  
Lung Cancers

The PACIFIC trial of durvalumab administered for 1 year to patients with stage III lung cancers has set a new standard of care. PACIFIC established the role of immune checkpoint inhibitors (ICIs) for individuals with inoperable and unresectable locally advanced lung cancers that achieve disease control from concurrent chemoradiation. For patients with resectable and operable disease, ICIs administered before surgery, either alone (JHU/MSK, LCMC3, and NEOSTAR) or in combination with chemotherapy (Columbia/MGH and NADIM), have yielded high rates of major pathologic response in resection specimens, an outcome measure that correlates with improved progression-free survival and overall survival. These results have brought forth the dilemma of how to choose the optimal local therapy—either definitive concurrent chemoradiation or surgery—to use with an ICI for patients with stage III lung cancers that are both operable and resectable. Here, we review the data that support the use of each local therapy. Recent successes have also raised the possibility that using ICIs in patients with earlier stages of lung cancer will enhance curability. Randomized trials are underway; however, until they read out, physicians must choose between local and systemic therapies on the basis of the information we have today. Research demonstrates that using surgery, radiation, chemotherapy, and ICIs improve all efficacy outcomes and curability. All modalities should be considered in every patient with locally advanced lung cancer. It is imperative that a multimodality discussion that includes the possible addition of ICIs takes place to choose the best modality and sequence of therapies for each patient.

scholarly journals Clinical and molecular factors that impact the efficacy of first-line crizotinib in ROS1-rearranged non-small-cell lung cancer: a large multicenter retrospective study

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yongchang Zhang ◽  
Xiangyu Zhang ◽  
Ruiguang Zhang ◽  
Qinqin Xu ◽  
Haiyan Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Retrospective Study ◽  
Brain Metastasis ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Driver Mutations ◽  
Advanced Lung Cancer ◽  
First Line ◽  
Lung Cancers ◽  
Chemotherapy Patients

Abstract Background ROS1-rearranged lung cancers benefit from first-line crizotinib therapy; however, clinical and molecular factors that could affect crizotinib efficacy in ROS1-rearranged lung cancers are not yet well-elucidated. Our retrospective study aimed to compare the efficacy of chemotherapy and crizotinib in the first-line treatment of ROS1-rearranged advanced lung cancer and evaluate various clinical and molecular factors that might impact crizotinib efficacy in real-world practice. Methods Treatment responses, survival outcomes, and patterns of disease progression were analyzed for 235 patients with locally advanced to advanced disease who received first-line chemotherapy (n = 67) or crizotinib (n = 168). Results The overall response rate was 85.7% (144/168) for first-line crizotinib and 41.8% (28/67) for chemotherapy. Patients treated with first-line crizotinib (n = 168) had significantly longer median progression-free survival (PFS) than chemotherapy (n = 67) (18.0 months vs. 7.0 months, p < 0.001). Patients harboring single CD74-ROS1 (n = 90) had significantly shorter median PFS with crizotinib than those harboring non-CD74 ROS1 fusions (n = 69) (17.0 months vs. 21.0 months; p = 0.008). Patients with baseline brain metastasis (n = 45) had a significantly shorter PFS on first-line crizotinib than those without brain metastasis (n = 123) (16.0 months vs. 22.0 months; p = 0.03). At progression, intracranial-only progression (n = 40), with or without baseline CNS metastasis, was associated with longer median PFS than those with extracranial-only progression (n = 64) (19.0 months vs. 13.0 months, p < 0.001). TP53 mutations were the most common concomitant mutation, detected in 13.1% (7/54) of patients with CD74-ROS1 fusions, and 18.8% (6/32) with non-CD74 ROS1 fusions. Patients with concomitant TP53 mutations (n=13) had significantly shorter PFS than those who had wild-type TP53 (n = 81) (6.5 months vs. 21.0 months; p < 0.001). PFS was significantly shorter for the patients who harbored concomitant driver mutations (n = 9) (11.0 months vs 24.0 months; p = 0.0167) or concomitant tumor suppressor genes (i.e., TP53, RB1, or PTEN) (n = 25) (9.5 months vs 24.0 months; p < 0.001) as compared to patients without concomitant mutations (n = 58). Conclusion Our results demonstrate that baseline brain metastatic status and various molecular factors could contribute to distinct clinical outcomes from first-line crizotinib therapy of patients with ROS1-rearranged lung cancer. Clinical trials registration CORE, NCT03646994

scholarly journals Achievement of long-term local control after radiation and anti-PD-1 immunotherapy in locally advanced non-small cell lung cancer

2021 ◽  
Vol 12 ◽  
pp. 204062232110473
Author(s):  
Zhao Jing ◽  
Rongjin Zhou ◽  
Ni Zhang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Curative Therapy

Although concurrent chemoradiotherapy (CRT) is recommended as standard of care in patients with locally advanced, unresectable, stage III non-small cell lung cancer (NSCLC), many patients who refuse or are not eligible for chemotherapy received radiotherapy (RT) alone with 5-year overall survival (OS) rate of about 5–6%. Immune-checkpoint inhibitors have demonstrated objective antitumor responses in patients with advanced NSCLC, but it is unclear how these agents can be used in the curative therapy with concurrent radiation. We report three cases of stage III unresectable NSCLC patients who refused chemotherapy received radiation and pembrolizumab immunotherapy. All patients had no local-regional recurrence with acceptable tolerance.

Systemic and Radiation Therapy Approaches for Locally Advanced Non–Small-Cell Lung Cancer

2022 ◽  
Author(s):  
Kristin A. Higgins ◽  
Sonam Puri ◽  
Jhanelle E. Gray
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Concurrent Chemoradiation ◽  
Driver Mutations ◽  
Small Cell Lung

The treatment for locally advanced non–small-cell lung cancer has changed dramatically over the past several years, with consolidative immunotherapy after concurrent chemoradiation becoming the new standard of care. Five-year survival outcomes have substantially improved with this approach. Despite these advances, further improvements are needed as the majority of patients ultimately develop progression of disease. The next-generation immunotherapy trials are currently being conducted that include approaches such as concurrent immunotherapy and addition of other therapeutic agents in the concurrent and consolidative settings. Specific unmet needs continue to exist for patients who develop disease progression after concurrent chemoradiation and immunotherapy, as well as defining the best treatment for patients with driver mutations. Future directions also include refinement of radiation techniques to reduce toxicities as much as possible, as well as the use of circulating tumor DNA in the surveillance setting. The current scientific landscape shows promising approaches that may further improve outcomes for patients with locally advanced non–small-cell lung cancer.

scholarly journals Immunoradiotherapy as an Effective Therapeutic Strategy in Lung Cancer: From Palliative Care to Curative Intent

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2178 ◽  
Author(s):  
Rodolfo Chicas-Sett ◽  
Juan Zafra-Martin ◽  
Ignacio Morales-Orue ◽  
Juan Castilla-Martinez ◽  
Miguel A. Berenguer-Frances ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Tumor Stage ◽  
Curative Intent ◽  
Therapeutic Modalities ◽  
Improve Patient Selection ◽  
Effective Therapeutic Strategy

Lung cancer is one of the main causes of cancer-related mortality worldwide. Over the years, different therapeutic modalities have been adopted depending on tumor stage and patient characteristics, such as surgery, radiotherapy (RT), and chemotherapy. Recently, with the development of immune-checkpoint inhibitors (ICI), the treatment of metastatic and locally advanced non-small cell lung cancer (NSCLC) has experienced a revolution that has resulted in a significant improvement in overall survival with an enhanced toxicity profile. Despite this paradigm shift, most patients present some kind of resistance to ICI. In this setting, current research is shifting towards the integration of multiple therapies, with RT and ICI being one of the most promising based on the potential immunostimulatory synergy of this combination. This review gives an overview of the evolution and current state of the combination of RT and ICI and provides evidence-based data that can improve patient selection. The combination in lung cancer is a safe therapeutic approach that improves local control and progression-free survival, and it has the potential to unleash abscopal responses. Additionally, this treatment strategy seems to be able to re-sensitize select patients that have reached a state of resistance to ICI, further enabling the continuation of systemic therapy.

scholarly journals Combination of chemoradiation therapy with immunotherapy in the treatment of patients with inoperable stage III non-small cell lung cancer

2020 ◽  
pp. 209-214
Author(s):  
N. V. Marinichenko ◽  
K. K. Laktionov ◽  
A. V. Nazarenko ◽  
E. V. Reutova ◽  
Merab S. Ardzinba ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Locally Advanced ◽  
Small Cell ◽  
Chemoradiation Therapy ◽  
Concurrent Chemoradiation ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Concurrent Chemoradiation Therapy

For more than 10 years, there have been no significant improvements in treatment outcomes for patients with inoperable locally advanced non-small cell lung cancer. At the moment, the standard of treatment for this category of patients is concurrent chemoradiation therapy. At the same time, the 5-year overall survival rate varies in the range of 15–25%. This indicator contributes to the modernization of existing approaches, as well as the search for new ways in the treatment of patients with inoperable stage III non-small cell lung cancer.One of the promising areas is the combination of chemoradiation therapy with immunotherapy. Thus, the use of Imfinzi (durvalumab, AstraZeneca) as a consolidation therapy in the Phase III clinical trial PACIFIC demonstrated a reduction in the risk of death by about one third in comparison with the standard approach.We present a clinical case study of a patient with locally advanced non-small cell lung cancer who received treatment in the framework of concurrent chemoradiation therapy followed by immunotherapy with durvalumab, continuing until now. The result of the therapy is the complete response to the specific treatment, recorded according to PET-CT.Thus, the use of immunotherapy as consolidation therapy represents a promising strategy for improving outcomes after concurrent chemoradiation therapy in patients with inoperable stage III non-small cell lung cancer

scholarly journals Prognostic factors of patients with advanced lung cancer treated with anlotinib: a retrospective cohort study

2021 ◽  
Vol 49 (10) ◽  
pp. 030006052110461
Author(s):  
Bijun Fan ◽  
Xiaoming Tan ◽  
Yueyan Lou ◽  
Yu Zheng ◽  
Liyan Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Locally Advanced ◽  
Prognostic Nutritional Index ◽  
Progression Free Survival ◽  
Advanced Lung Cancer ◽  
Rank Test ◽  
Factors Affecting ◽  
Kaplan Meier ◽  
Hand Foot Syndrome ◽  
Cox Proportional Hazard Regression

Objective Our study aimed to evaluate the main factors affecting the efficacy of anlotinib to determine the therapeutically dominant populations. Methods The medical records of patients with lung cancer who were treated with anlotinib from July 2018 to February 2020 at Renji Hospital, School of Medicine, Shanghai Jiaotong University were retrospectively reviewed. The optimal cutoff prognostic nutritional index (PNI) value for predicting efficacy was determined according to receiver operating characteristic curves. Progression-free survival (PFS) and overall survival (OS) were calculated and compared using the Kaplan–Meier method and log‐rank test. The prognostic values of each variable were evaluated with univariate and multivariate Cox proportional hazard regression analyses. Results The overall disease control rate of 44 patients with lung cancer was 93.2% (41/44). The median PFS was 5.0 months (95% [confidence interval] CI: 2.2–7.8), and the median OS was 6.5 months (95% CI: 3.6–9.3). The multivariate analysis results indicated that hand–foot syndrome and high PNI values were independent protective factors of PFS and OS. Conclusions Anlotinib was effective in treating locally advanced or advanced lung cancer. High pretreatment PNI scores and the presence of hand–foot syndrome after treatment were independent prognostic markers for favorable OS and PFS.

scholarly journals Achievement of Long-term Local Control After Concurrently With Radiation and Anti-PD-1 Immunotherapy in Locally Advanced Non-small Cell Lung Cancer Patients

2020 ◽  
Author(s):  
zhao jing ◽  
Rongjin Zhou ◽  
Huaxiang He ◽  
Shixiu Wu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Case Series ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract Background: Although concurrent chemoradiotherapy (CRT) was recommend as standard of care in patients with stage III unresectable non-small cell lung cancer (NSCLC), many patients refused or were not eligible for chemotherapy in clinical practice. These patients often receive RT alone with 5-year OS rate of about 5-6%. This addressed a common clinical challenge of treating these patients. Immune-checkpoint inhibitors have demonstrated objective antitumor responses in patients with advanced NSCLC, but it is unclear how these agents can be used in the curative therapy with concurrent radiation. Case presentation: Here we described, the case series, the effect of stage III unresectable NSCLC patients who refused chemotherapy received radiation and anti-PD-1 immunotherapy. Three patients with stage III unresectable NSCLC were treated with radiotherapy concurrently with anti-PD-1 agent (pembrolizumab) between May 2018 and August 2018 in our hospital. Two patients experienced partial response and one patient experienced stable disease. One patient developed the liver metastasis 4 months after the treatment. All patients had no local-regional recurrence. No patient experienced ≥ grade 3 adverse event (AE), and no patient discontinued treatment because of an AE. Conclusions: Concurrent treatment with radiation and pembrolizumab for unresectable stage III NSCLC patients who refused chemotherapy demonstrated its efficacy and acceptable tolerance. Further investigations are warranted to determine its role in the management of these patients.

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