Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer

Gandhi, Leena; Rodríguez-Abreu, Delvys; Gadgeel, Shirish M.; Esteban, Emilio; Felip, Enriqueta; Angelis, F. De; Dómine, Manuel; Clingan, Philip R.; Hochmair, Maximilian; Powell, Steven; Cheng, Susanna Y.; Bischoff, Helge; Peled, Nir; Grossi, Francesco; Jennens, Ross; Reck, Martin; Hui, Rina; Garon, Edward B.; Boyer, Michael; Rubio-Viqueira, Belén; Novello, Silvia; Kurata, Takeshi; Gray, Jhanelle E.; Vida, John; Wei, Ziwen; Yang, Jing; Raftopoulos, Harry; Pietanza, M. Catherine; Garassino, Marina Chiara

doi:10.1056/nejmoa1801005

Cited by 5,212 publications

(4,762 citation statements)

References 30 publications

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“…In the context of this concern, overall survival may be a better indicator than tumor response rate to appraise the impact of tumor-specific memory formation. It is encouraging that anti-PD therapy plus chemotherapy showed an improved overall survival over chemotherapy alone during a short period of time (1–2 years) (Gandhi et al, 2018). It is more important to compare this combination therapy with anti-PD therapy alone, as well as the evaluation of the generation of memory T cells, a major force for durable immune responses.…”

Section: The Principles To Combine Other Therapeutics With Anti-pd Thmentioning

confidence: 99%

A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization

Sanmamed

Chen

2018

Cell

1,077

557

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Harnessing an antitumor immune response has been a fundamental strategy in cancer immunotherapy. For over a century, efforts have primarily focused on amplifying immune activation mechanisms that are employed by humans to eliminate invaders such as viruses and bacteria. This “immune enhancement” strategy often results in rare objective responses and frequent immune-related adverse events (irAEs). However, in the last decade, cancer immunotherapies targeting the B7-H1/PD-1 pathway (anti-PD therapy), have achieved higher objective response rates in patients with much fewer irAEs. This more beneficial tumor response-to-toxicity profile stems from distinct mechanisms of action that restore tumor-induced immune deficiency selectively in the tumor microenvironment, here termed “immune normalization,” which has led to its FDA approval in more than 10 cancer indications and facilitated its combination with different therapies. In this article, we wish to highlight the principles of immune normalization and learn from it, with the ultimate goal to guide better designs for future cancer immunotherapies.

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Section: The Principles To Combine Other Therapeutics With Anti-pd Thmentioning

confidence: 99%

A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization

Sanmamed

Chen

2018

Cell

1,077

557

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“…51 In addition, the study sampled patients before the adaptation of front-line chemoimmunotherapy, which is why patients were analyzed by treatment types that did not account for chemo-immunotherapy. 52 …”

Section: Discussionmentioning

confidence: 99%

C‐reactive protein and its association with depression in patients receiving treatment for metastatic lung cancer

McFarland

Shaffer

Breitbart

et al. 2018

Cancer

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BACKGROUND: Depression is highly prevalent in lung cancer. Although there is a known association between inflammation and depression, this relationship has not been examined in patients with lung cancer who undergo treatment with immune and other targeted drug therapies. Peripheral blood C-reactive protein (CRP), a marker of systemic inflammation, may help identify metastatic lung cancer patients with inflammation-associated depression. METHOD: Patients with metastatic lung cancer undergoing treatment were evaluated for depression using the Hospital Anxiety and Depression Scale (HADS). Inflammation (CRP and CRP cutoffs ≥1 and ≥3 mg/mL) and demographic and treatment variables were analyzed for association with depression. RESULTS: One hundred nine consecutive participants exhibited an average plasma CRP concentration of 1.79 mg/mL (median, 0.75 mg/mL [standard deviation, 2.5 mg/mL), and 20.7% had a CRP concentration of ≥3.0 mg/mL; 23.9% met depression screening criteria (HADS ≥8). A log transformation of CRP was significantly correlated with depression severity (r = 0.47, P < .001). CRP was the only covariate to predict depression severity (P = .008) in a multivariate model including lung cancer disease subtype and type of systemic treatment. Receiver operating characteristic analysis indicated that CRP had moderate predictive accuracy in identifying elevated depression (area under the curve = 0.74). A cutoff of CRP ≥3.0 generated high specificity (88%) but identified only 50% of those with elevated depression. CONCLUSION: Elevated CRP is associated with depression in patients with metastatic lung cancer. Thus, CRP may identify a subset of lung cancer patients with inflammation-induced depression and may be useful in predicting response to treatments that target inflammation or its downstream mediators on the brain.

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“…56 The clinical standard platinum-based doublet chemotherapy is now in clinical trial with combinations of ipilimumab and pembrolizumab (NCT03515629). 56 The clinical standard platinum-based doublet chemotherapy is now in clinical trial with combinations of ipilimumab and pembrolizumab (NCT03515629).…”

Section: Icpb Therapy In Combination With Chemotherapy and Radiotherapymentioning

confidence: 99%

The role and therapeutic implications of T cells in cancer of the lung

2019

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Lung cancer remains the leading cause of cancer‐related death worldwide. The disease is classified into two major subtypes, small‐cell lung cancer (SCLC) and the more prevalent non‐small‐cell lung cancer (NSCLC). First‐line conventional therapies, such as chemotherapy, radiotherapy and surgery, have offered limited benefit, and patient prognosis remains poor with post‐treatment recurrences representing a major cause of morbidity. Consequently, there is an urgent need for improved therapeutic options. Historically, NSCLC has been considered a non‐immunogenic disease. However, increased understanding of tumor‐immune interactions has challenged this paradigm in both lung and other malignancies, with cancer elimination by tumor‐specific T cells increasingly well described in a myriad of solid tumors. Recent evidence has demonstrated that absent or weak anticancer responses are likely a product of tumor‐derived immunosuppression. This knowledge, along with a greater appreciation for the role of T cells in lung cancer elimination, has driven development of novel immunotherapeutic approaches which are demonstrating remarkable clinical efficacy. This review examines the role of T cells in lung cancer, discussing the direction and clinical significance of current and future immunotherapeutic strategies.

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Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer

Cited by 5,212 publications

References 30 publications

A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization

A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization

C‐reactive protein and its association with depression in patients receiving treatment for metastatic lung cancer

The role and therapeutic implications of T cells in cancer of the lung

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