Clinical and Molecular Characteristics Associated With Survival Among Patients Treated With Checkpoint Inhibitors for Advanced Non–Small Cell Lung Carcinoma

Lee, Chee Khoon; Man, Johnathan; Lord, Sarah J.; Cooper, Wendy A.; Links, Matthew; Gebski, Val; Herbst, Roy S.; Gralla, Richard J.; Mok, Tony; Yang, James Chih‐Hsin

doi:10.1001/jamaoncol.2017.4427

Cited by 469 publications

(364 citation statements)

References 36 publications

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“…This conclusion is supported by results of a recent meta-analysis of many of these trials [104]. Current data do not support use of these drugs in patients with PS ≥2 who should be offered entry into a clinical trial if possible.…”

Section: Resultsmentioning

confidence: 95%

Patient Selection for Anti-PD-1/PD-L1 Therapy in Advanced Non-Small-Cell Lung Cancer: Implications for Clinical Practice

et al. 2018

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Immune checkpoint inhibitors targeting PD-1 or PD-L1 represent a standard treatment option for patients with advanced non-small-cell lung cancer. However, a substantial proportion of patients will not benefit from these treatments, and robust biomarkers are required to help clinicians select patients who are most likely to benefit. Here, we discuss the available evidence on the utility of clinical characteristics in the selection of patients with advanced non-small-cell lung cancer as potential candidates for single-agent anti-PD-1/PD-L1 therapy, and provide practical guidance to clinicians on identifying those patients who are most likely to benefit. Recommendations on the use of immune checkpoint inhibitor in clinically challenging populations are also provided.

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Section: Resultsmentioning

confidence: 95%

Patient Selection for Anti-PD-1/PD-L1 Therapy in Advanced Non-Small-Cell Lung Cancer: Implications for Clinical Practice

et al. 2018

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“…A major driving gene in the development and progression of NSCLC is the epithelial growth factor receptor ( EGFR ). The two major mutations in EGFR are deletions in exon 19 (present in 45% of patients with EGFR mutation) and a point mutation in exon 21 (in 40% of patients with EGFR mutation), and both are associated with the constitutive activation of the tyrosine kinase domain . These sensitizing EGFR mutations are present in 10% of Caucasian patients and 50% of Asian patients .…”

Section: Introductionmentioning

confidence: 99%

“…These sensitizing EGFR mutations are present in 10% of Caucasian patients and 50% of Asian patients . Patients with NSCLC harboring a sensitizing EGFR mutation have shorter survival, higher frequency of lymph node metastasis, and poorer response to chemotherapy . Fortunately, tyrosine kinase inhibitors (TKIs) are available and the patients with sensitizing EGFR mutations will respond to the TKIs, but resistance will eventually occur due to TKI‐resistant mutations in EGFR , or to mutations arising in other genes such as KRAS and BRAF …”

Section: Introductionmentioning

confidence: 99%

“…Therefore, determining the original EGFR mutation status and monitoring the changes in mutations is crucial to the management of NSCLC, but biopsies are invasive procedures and can be technically impossible in some patients. So far, the concept of liquid biopsy has expanded from blood‐based resources to urine, saliva, effusion, cerebrospinal fluid and other body fluid, which acts as a simple, fast and cost efficient alternative for monitoring of disease status, or response to treatment in multiple malignancies, including lung cancer .…”

Section: Introductionmentioning

confidence: 99%

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Detection of EGFR gene mutation status from pleural effusions and other body fluid specimens in patients with lung adenocarcinoma

Zhang

Tang

et al. 2019

Thoracic Cancer

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Background Epidermal growth factor receptor (EGFR) gene mutation status is essential to the optimal management of lung adenocarcinoma. Liquid biopsy has advantages such as noninvasiveness, speediness, and convenience. This study aimed to detect EGFR gene mutations using next‐generation sequencing (NGS) from different types of body fluids from patients with lung adenocarcinoma. Methods This was a prospective study of 20 patients with lung adenocarcinoma recruited between January 2017 and December 2018 at the Beijing Hospital. All patients had adenocarcinoma with confirmed sensitizing EGFR mutations. Body fluid specimens included pleural effusion, ascites, pericardial effusion, and cerebrospinal fluid. NGS was conducted to test for nine lung cancer‐related gene in body fluid supernatant free DNA, sedimentary tumor cells, and plasma free DNA. Results The EGFR gene mutation abundance of body fluid supernatant free DNA was higher than that of body fluid sedimentary tumor cells and plasma free DNA specimens (100% vs. 90% vs. 80%, respectively, all P < 0.05). The results of EGFR mutation from the body fluid supernatants were consistent with the results from the tissue biopsy. Conclusions This study showed that compared with body fluid sediment tumor cells and plasma free DNA samples, body fluid supernatant free DNA has a higher detection rate and sensitivity of tumor‐specific mutations. Free DNA obtained from body fluid supernatants could be used as high‐quality specimens for gene mutation detection in patients with lung cancer. This could be applied in treatment decisions and patient management.

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“…Patients with EGFR mutations and ALK rearrangements appear to be less responsive to immune checkpoint blockade, presumably due to a lower tumour mutational burden. This has been demonstrated in pooled subgroup analyses of several large randomised trials for immune checkpoint inhibitors (ICI) versus docetaxel chemotherapy in NSCLC; no survival benefit was found in patients with EGFR mutations . Subsequent studies have explored various combinations of TKI therapy and ICI; however, high rates of severe hepatotoxicity and interstitial pneumonitis, as well as lack of improvement in response rates, have led to premature termination of several trials and uncertainty regarding the clinical feasibility of these combinations.…”

Section: Discussionmentioning

confidence: 99%

RET‐rearranged non‐small‐cell lung cancer and therapeutic implications

Loh

Mitchell

John

et al. 2019

Internal Medicine Journal

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First‐line tyrosine kinase inhibitors are standard of care for non‐small‐cell lung cancers (NSCLC) harbouring an epidermal growth factor receptor mutation, anaplastic lymphoma kinase fusion or c‐ros oncogene 1 rearrangement. Other targetable oncogenic drivers have been identified but testing for these is neither funded nor commonly performed in Australia. Using a case example, we discuss the importance of considering several other genomic aberrations in our population, such as rearrangements in the RET proto‐oncogene, which occur in 1–2% of lung adenocarcinoma. New oncogenic drivers and corresponding targeted agents are constantly being discovered; these will continue to refine the treatment of non‐small‐cell lung cancer in the era of precision medicine.

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Clinical and Molecular Characteristics Associated With Survival Among Patients Treated With Checkpoint Inhibitors for Advanced Non–Small Cell Lung Carcinoma

Cited by 469 publications

References 36 publications

Patient Selection for Anti-PD-1/PD-L1 Therapy in Advanced Non-Small-Cell Lung Cancer: Implications for Clinical Practice

Patient Selection for Anti-PD-1/PD-L1 Therapy in Advanced Non-Small-Cell Lung Cancer: Implications for Clinical Practice

Detection of EGFR gene mutation status from pleural effusions and other body fluid specimens in patients with lung adenocarcinoma

RET‐rearranged non‐small‐cell lung cancer and therapeutic implications

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