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 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.

Immune-related toxicities in non-small cell lung cancer: Real-life predictors of outcome to checkpoint inhibitors?

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14135-e14135
Author(s):  
Emanuela Romano ◽  
Roberta Poli ◽  
Clement Dumont ◽  
Lisa Pietrogiovanna ◽  
Marie Vigan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Real Life ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Dermatologic Toxicity

e14135 Background: Immune checkpoint inhibitors (ICIs) are approved for the treatment of non-small cell lung cancer (NSCLC) and are associated with immune-related adverse events (irAEs). However, real-life data on type, occurrence and kinetics of irAEs, and their predictive value on treatment outcome are lacking. Here, we report on the relation between irAEs, including endocrine irAEs, and outcome to anti-PD-/L-1 (programmed cell death protein-/ligand-1) ICIs. Methods: A total of 147 patients (pts), with locally advanced/metastatic NSCLC, treated with anti-PD-1 (N 140; 95%) or anti-PD-L1 agents (N 7; 5%) as ≥ 2 line treatment were included in two independent, prospective, cohorts at the Institut Curie (ALCINA-NCT02866149) and at Biella Hospital (Italy). PD-L1 status was assessed by immunohistochemistry (clone 22C3, Dako). Progression-free survival (PFS) and overall survival (OS) were estimated with Kaplan-Meier curves. Results: Median follow-up of 147 pts was 10.2 (range: 0.7-42.8) months; median age, 66 (35-85) years; 100 men (68%). After treatment initiation, irAEs were observed in 72 pts (49%). Thirty one (43%) pts had only endocrine irAEs, mostly thyroid dysfunctions (N 44, 61%). Pre-existing thyroid disease was present in only 6 pts (4%). Dermatologic toxicity in 21 (29%) pts was the next most frequent irAE, 22 (30%) pts had other types of irAEs. Among patients with irAEs, 61 (85%) had ≤ 2 coexisting irAEs, and 13 (18%) pts had > 2 irAEs. Most irAEs were G1 (63%) and G2 (18%). Onset and kinetics differed according to irAE type. There was no association between PD-L1 status and irAE occurrence. Median PFS was 7.2 and 4.2 months in irAEs vs no-irAEs group, respectively [HR 0.70 (95% CI 0.46;1.08), p 0.11]. Median OS in the irAEs group was 18.1 months vs 13.6 months no-irAEs group [HR 0.64 (95% CI 0.37;0.98), p 0.039]. Median OS in the endocrine-irAEs group was 23.5 vs 13.6 months in the no-irAEs group [HR 0.58 (0.74;3.92), p 0.2]. Conclusions: In this study, we show that irAEs – including endocrine type – are frequent in NSCLC pts treated with ICIs and that their occurrence is associated with a survival benefit.

scholarly journals Clinical outcome and side effects of concomitant chemoradiotherapy in the treatment of locally advanced inoperable non-small cell lung cancer: Our experiences

2021 ◽  
pp. 38-38
Author(s):  
Bojan Radojicic ◽  
Marija Radojicic ◽  
Miroslav Misovic ◽  
Dejan Kostic
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Concomitant Chemoradiotherapy ◽  
Free Survival

Background/Aim. About 1.8 million new lung cancer cases are diagnosed in the world every year, and about 1.6 million cases are with fatal outcome. Despite improvements in treatment in previous decades, the survival of patients with lung cancer is still poor. The five-year survival rate is about 50% for patients with localized disease, 20% for patients with regionally advanced disease, 2% for patients with metastatic disease, and about 14% for all stages. The median survival of patients with untreated NSCLC in the advanced stage is four to five months and the annual survival rate is only 10%. The main goal of the research is to obtain and analyze the results of treatment with concomitant chemotherapy in terms of its efficacy and toxicity in selected patients with locally advanced inoperable non-small cell lung cancer. Methods. The study included data analysis of 31 patients of both sexes who were diagnosed and pathohistologically verified with NSCLC in inoperable stage III and were referred by the Council for Malignant Lung Diseases to the Radiotherapy Department of the Military Medical Academy for concomitant chemoradiotherapy treatment. Upon expiry of the three-month period from the performed radiation treatment, the tumor resonance was assessed on the basis of MSCT examination of the chest and upper abdomen according to RECIST 1.1 criteria (Response Evaluation Criteria in Solid Tumors). According to the same criteria, progression-free survival (PFS) was also assessed every three months during the first two years, then every 6 months or until the onset of disease symptoms, as well as overall survival (OS). Result. The median progression-free survival is 13 months, and the median overall survival is 20 months. During and immediately after RT, 9 (29%) patients had a grade 2 or higher adverse event. Conclusion. The use of concomitant chemoradiotherapy in patients in the third stage of locally advanced inoperable non-small cell lung cancer provides a good opportunity for a favorable therapeutic outcome, with an acceptable degree of acute and late toxicity, and represents the standard therapeutic approach for selected patients in this stage of the disease.

Investigate the efficacy of immunotherapy for treatment of pancreatic adenocarcinoma (PDAC) with mismatch repair deficiency (dMMR).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 415-415
Author(s):  
Arish Noor ◽  
Luis E. Aguirre ◽  
Kirsten Blue ◽  
Trenton Avriett ◽  
Estrella M. Carballido ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Metastatic Disease ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Median Number ◽  
Cancer Center ◽  
Duration Of Response

415 Background: Immune checkpoint inhibitors (ICI) have been approved in solid tumors with dMMR. However, only limited data are available for PDAC with dMMR given the rarity of dMMR in PDAC. We evaluated efficacy of ICIs in PDAC with dMMR. Methods: Retrospective clinical and pathologic data were collected for patients (pts) with pancreatic adenocarcinoma from May 2017 to June 2020 at Moffitt cancer center. Results: We identified 10 pts with dMMR PDAC. The median age was 64.5 years (range: 42-86) and 4 pts were male. 4 pts had resectable disease, 3 had locally advanced and 3 had metastatic disease at initial diagnosis. MSH6 deficiency (def) was found in 2 cases, PMS2 def in 2, MLH/PMS2 def in 5, and MSH2/MSH6 in 1. 7 pts were treated with ICIs. 3 pts had locally advanced and 4 had metastatic disease when they started ICIs. 5 received Pembrolizumab (pem), 1 received ipilimumab/ nivolumab (ipi/nivo), and 1 received pem then ipi/nivo after progressive disease (PD) on pem. The median number of prior lines of chemotherapy was 1 (range 0-2). 6 pts were evaluable, and 1 had rapid disease progression after 1 dose of pem. Among 6 evaluable pts, 3 had an objective response (1: complete response and 2: partial response), and 2 had stable disease (SD). Median progression-free survival was 8.2 mo, and median overall survival was not reached with median follow-up (FU) of 6.8 mo. The median duration of response was not reached with a median FU of 22.6 mo. The pt with CR remained disease-free for up to 22 months. The pt whose treatment was switched to ipi/nivo after PD on pem achieved SD > 4mo on ipi/nivo. While on immunotherapy, one patient with ipi/nivo developed immunotherapy associated rash requiring systemic steroids, and another on pem developed hypothyroidism requiring levothyroxine. Conclusions: This series suggest ICIs can provide durable clinical efficacy in pts with dMMR PDAC.

scholarly journals Radiotherapy Scheme Effect on PD-L1 Expression for Locally Advanced Rectal Cancer

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2071
Author(s):  
Jihane Boustani ◽  
Valentin Derangère ◽  
Aurélie Bertaut ◽  
Olivier Adotevi ◽  
Véronique Morgand ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Regression ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Tumor Regression Grade ◽  
The Impact

In locally advanced rectal cancer, radiotherapy (RT) followed by surgery have improved locoregional control, but distant recurrences remain frequent. Although checkpoint inhibitors have demonstrated objective response in several cancers, the clinical benefit of PD-1/PD-L1 blockade remains uncertain in rectal cancer. We collected data from biopsies and surgical specimens in 74 patients. The main objective was to evaluate the impact of neoadjuvant RT and fractionation on PD-L1 expression. Secondary objectives were to study the relation between PD-L1 expression and tumor regression grade (TRG), progression-free survival (PFS), overall survival (OS), and CD8 TILs infiltration. Median rates of cells expressing PD-L1 pre- and post-RT were 0.15 (range, 0–17) and 0.5 (range, 0–27.5), respectively (p = 0.0005). There was no effect of RT fractionation on PD-L1+ cell rates. We found no relation between CD8+ TILs infiltration and PD-L1 expression and no difference between high-PD-L1 or low-PD-L1 expression and TRG. High-to-high PD-L1 expression profile had none significant higher OS and PFS compared to all other groups (p = 0.06). Median OS and PFS were higher in biopsies with >0.08 PD-L1+ cells. High-to-high PD-L1 profile and ypT0-2 were significantly associated with higher OS and PFS. This study did not show the differential induction of PD-L1 expression according to fractionation.

scholarly journals P2.18-03 Salvage Surgery After Curative-Intent Chemo and/or Radiation for Locally Advanced Lung Cancer

2019 ◽  
Vol 14 (10) ◽  
pp. S903
Author(s):  
M. Yamashita ◽  
Y. Maki ◽  
T. Ueno ◽  
H. Suehisa ◽  
D. Harada ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Salvage Surgery ◽  
Locally Advanced ◽  
Advanced Lung Cancer ◽  
Curative Intent ◽  
Locally Advanced Lung Cancer

The effect and safety of immune checkpoint inhibitor rechallenge in non-small cell lung cancer

2019 ◽  
Vol 49 (8) ◽  
pp. 762-765 ◽  
Author(s):  
Hiromi Watanabe ◽  
Toshio Kubo ◽  
Kiichiro Ninomiya ◽  
Kenichiro Kudo ◽  
Daisuke Minami ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Careful Consideration ◽  
Small Cell ◽  
Small Cell Lung

Abstract Introduction Immune checkpoint inhibitors (ICIs) have demonstrated long survival for the treatment of advanced non-small cell lung cancer (NSCLC). However, the effect and safety of ICI rechallenge have not been fully evaluated. The aim of this study was to investigate the efficacy and safety of ICI rechallenge in NSCLC patients. Methods We defined ‘rechallenge’ as re-administration of ICIs for patients who were previously treated with ICIs and discontinued treatment for any reason, and received subsequent chemotherapy. We retrospectively analyzed the histories of 434 patients with advanced NSCLC who received ICIs from December 2015 to December 2017 at seven centers. Results A total of 317 patients discontinued the ICI treatment, and 14 patients (4.4%) received ICI rechallenge. All 14 patients discontinued the first ICI due to disease progression. Eight patients received the same kind of ICIs, and six patients received different ICIs. Median progression-free survival and overall survival were 1.5 months [95% confidence interval (CI): 0.8–2.6] and 6.5 months [95% CI: 1.4–19.0], respectively. The objective response rate was 7.1%, and the disease control rate was 21.4%. Two of three patients who achieved at least a stable disease, received radiotherapy between the first and second ICIs. Adverse events were not significantly different compared with the first ICIs. Conclusions In this study, the effect of ICI rechallenge was limited. Careful consideration of the administration of ICI rechallenge is necessary. This report involved a small number of cases, so further large prospective studies are warranted to confirm the efficacy of ICI rechallenge and to investigate predictive markers to identify a patient population in which ICI rechallenge is effective.

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