First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer

Horn, Leora; Mansfield, Aaron S.; Szczęsna, Aleksandra; Havel, Libor; Krzakowski, Maciej; Hochmair, Maximilian; Huemer, Florian; Losonczy, György; Johnson, Melissa L.; Nishio, Makoto; Reck, Martin; Mok, Tony; Lam, Sivuonthanh; Shames, David S.; Liu, Juan; Ding, Beiying; López-Chávez, Ariel; Kabbinavar, Fairooz; Lin, Weihong; Sandler, Alan; Liu, Stephen V.

doi:10.1056/nejmoa1809064

Cited by 2,555 publications

(2,597 citation statements)

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“…Future LS‐SCLC trials should prospectively assess the vulnerability of elderly patients to adverse events, incorporate novel methods of monitoring adverse events through patient‐reported outcomes, and investigate novel radiation treatments or systemic therapies . A phase 3 trial of carboplatin and etoposide alone or with atezolizumab in extensive‐stage SCLC revealed an improvement in OS . Recently, the US Food and Drug Administration approved single‐agent nivolumab for patients with extensive‐stage SCLC with disease progression after platinum‐based therapy and at least 1 other therapy .…”

Section: Discussionmentioning

confidence: 99%

“…36,40 A phase 3 trial of carboplatin and etoposide alone or with atezolizumab in extensive-stage SCLC revealed an improvement in OS. 41 Recently, the US Food and Drug Administration approved single-agent nivolumab for patients with extensive-stage SCLC with disease progression after platinum-based therapy and at least 1 other therapy. 42 Immunotherapy alone and in combination with chemotherapy has the potential to improve efficacy and may lead to fewer severe adverse events than the chemotherapy combinations investigated in these trials.…”

Section: Discussionmentioning

confidence: 99%

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A pooled analysis of individual patient data from National Clinical Trials Network clinical trials of concurrent chemoradiotherapy for limited‐stage small cell lung cancer in elderly patients versus younger patients

Stinchcombe

Fan

Schild

et al. 2018

Cancer

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Background Platinum and etoposide with thoracic radiation followed by prophylactic cranial irradiation constitute the standard treatment for limited‐stage small cell lung cancer (LS‐SCLC). Many patients with LS‐SCLC are elderly with comorbidities. Methods Individual patient data were collected from 11 phase 2 or 3 trials for LS‐SCLC conducted by the National Clinical Trials Network and activated from 1990 to 2010. The primary endpoint was overall survival (OS); the secondary endpoints were progression‐free survival (PFS), the rate of severe adverse events, and off‐treatment reasons. The outcomes were compared for patients 70 years old or older (elderly patients) and patients younger than 70 years (younger patients). Results Individual patient data from 1049 younger patients (81%) and 254 elderly patients (19%) were analyzed. In the multivariate model, elderly patients, in comparison with younger patients, had worse OS (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.18‐1.63; median OS for elderly patients, 17.8 months; OS for younger patients, 23.5 months) and worse PFS (HR, 1.19; 95% CI, 1.03‐1.39; median PFS for elderly patients, 10.6 months; median PFS for younger patients, 12.3 months). Elderly patients, in comparison with younger patients, experienced more grade 5 adverse events (8% vs 3%; P < .01) and more grade 3 or higher dyspnea (11% vs 7%; P = .03) but less grade 3 or higher esophagitis/dysphagia (14% vs 19%; P = .04) and less grade 3 or higher vomiting (11% vs 17%; P = .01). Elderly patients completed treatment less often, discontinued treatment because of adverse events and patient refusal more frequently, and died during treatment more frequently. Conclusions Elderly patients with LS‐SCLC have worse PFS and OS and more difficulty in tolerating therapy. Future trials should incorporate assessments of elderly patients, novel monitoring of adverse events, and more tolerable radiation and systemic therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A pooled analysis of individual patient data from National Clinical Trials Network clinical trials of concurrent chemoradiotherapy for limited‐stage small cell lung cancer in elderly patients versus younger patients

Stinchcombe

Fan

Schild

et al. 2018

Cancer

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“…Checkpoint inhibitor therapy (specifically, anti-programmed death-ligand 1 therapy) has proven remarkably effective in Merkel cell carcinoma (but only modestly so in visceral NECs), and has rapidly emerged as first-line therapy in the metastatic setting. [8][9][10] Unlike in adenocarcinomas, transcription factors are frequently expressed in NECs independently of site of origin-a phenotype referred to as 'transcription factor lineage infidelity'. 11 There is a precedent, however, for the value of a transcription factor in this diagnostic context (i.e.…”

Section: Introductionmentioning

confidence: 99%

SATB2 in neuroendocrine neoplasms: strong expression is restricted to well‐differentiated tumours of lower gastrointestinal tract origin and is most frequent in Merkel cell carcinoma among poorly differentiated carcinomas

Bellizzi

2019

Histopathology

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Aims Special AT‐rich sequence‐binding protein 2 (SATB2) is a transcriptional regulator with critical roles in brain, craniofacial and skeletal development. It has emerged as a key marker of lower gastrointestinal (GI) tract columnar epithelial and osteoblastic differentiation. Transcription factor immunohistochemistry is useful in assigning site of origin in well‐differentiated neuroendocrine tumours (NETs), and has had a limited role in poorly differentiated neuroendocrine carcinomas (NECs). This study sought to evaluate the role of SATB2 in assigning site of origin in neuroendocrine epithelial neoplasms. Methods and results Tissue microarrays were constructed from the following: 317 NETs (37 thyroid, 46 lung, 16 stomach, 12 duodenum, 70 pancreas, 106 jejunoileum, 24 appendix, and six rectosigmoid), 44 phaeochromocytomas/paragangliomas, and 79 NECs (29 Merkel cell, 30 lung, and 20 extrapulmonary visceral); nine appendiceal and 19 rectal NETs were examined in whole sections. SATB2 immunohistochemistry was scored for extent (%) and intensity (0–3+), with an H‐score being calculated. SATB2 was expressed by 96% of rectosigmoid NETs, 79% of appendiceal NETs, and only 7% of other well‐differentiated neoplasms (P < 0.0001). Expression in lower GI tract NETs (median H‐score of 255) was stronger than in other positive tumours (median H‐score of 7) (P < 0.0001). Any SATB2 expression was 86% sensitive/93% specific for lower GI tract origin. SATB2 was expressed by 79% of Merkel cell carcinomas (median H‐score of 300), 33% of lung NECs (median H‐score of 23), and 60% of extrapulmonary visceral NECs (median H‐score of 110), with stronger expression in Merkel cell carcinoma (P < 0.001). At an H‐score cutoff of ≥150, SATB2 was 69% sensitive/90% specific for Merkel cell carcinoma. Conclusions SATB2 is frequently and strongly expressed by lower GI tract NETs; we have adopted it as our rectal NET marker. Relatively frequent and strong expression in Merkel cell carcinoma may have value in assigning NEC site of origin.

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“…Adding chemotherapy to anti‐PD1/PD‐L1 therapy is a successful strategy to improve treatment efficacy in various types of cancer, including non‐small‐cell lung cancer (NSCLC), small cell lung cancer, and breast cancer . Chemotherapy may induce immunogenic cell death in the tumor, increase the release of neoantigen, and increase lymphocyte infiltration in the tumor microenvironment .…”

Section: Combination Therapy For Hnsccmentioning

confidence: 99%

Immune checkpoint inhibitors for head and neck squamous cell carcinoma: Current landscape and future directions

Kao

Lou

2019

Head & Neck

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Background Immune checkpoint inhibitors (ICIs) can reinvigorate T cells and activate the immune system to eliminate cancer cells. Head and neck squamous cell carcinoma (HNSCC) is a malignancy with a poor prognosis. The roles of ICIs for HNSCC treatments are emerging. Method We reviewed the study results of Programmed‐Death 1 (PD‐1) and PD‐ligand‐1 (PD‐L1) monoclonal antibodies for HNSCC. The ongoing trials of anti‐PD‐1 and anti‐PD‐L1 were also reviewed. Results Nivolumab showed a significant overall survival benefit in platinum‐refractory HNSCC patients. For platinum‐sensitive or first‐line patients, pembrolizumab monotherapy (patients with PD‐L1 Combined Positive Score ≥ 20) or pembrolizumab‐platinum‐fluorouracil improved overall survival vs the EXTREME (cetuximab‐platinum‐fluorouracil). Many HNSCC studies have combined anti‐PD1/PD‐L1 therapy with various anticancer agents or radiotherapy to improve treatment efficacy. Conclusion ICIs demonstrate their efficacies for R/M HNSCC patients. The incorporation of ICIs showed a great impact on the treatment landscape of HNSCC.

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First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer

Cited by 2,555 publications

References 25 publications

A pooled analysis of individual patient data from National Clinical Trials Network clinical trials of concurrent chemoradiotherapy for limited‐stage small cell lung cancer in elderly patients versus younger patients

A pooled analysis of individual patient data from National Clinical Trials Network clinical trials of concurrent chemoradiotherapy for limited‐stage small cell lung cancer in elderly patients versus younger patients

SATB2 in neuroendocrine neoplasms: strong expression is restricted to well‐differentiated tumours of lower gastrointestinal tract origin and is most frequent in Merkel cell carcinoma among poorly differentiated carcinomas

Immune checkpoint inhibitors for head and neck squamous cell carcinoma: Current landscape and future directions

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