Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial

Rittmeyer, Achim; Barlési, Fabrice; Waterkamp, Daniel; Park, Keunchil; Ciardiello, Fortunato; Pawel, Joachim von; Gadgeel, Shirish M.; Hida, Toyoaki; Kowalski, Dariusz M.; Dols, M. Cobo; Cortinovis, Diego; Leach, Joseph W.; Polikoff, Jonathan; Barrios, Carlos H.; Kabbinavar, Fairooz; Frontera, Osvaldo Arén; Marinis, Filippo de; Turna, Hande; Lee, Jong-Seok; Ballinger, Marcus; Kowanetz, Marcin; He, Pei; Chen, Daniel S.; Sandler, Alan; Gandara, David R.

doi:10.1016/s0140-6736(16)32517-x

Cited by 4,036 publications

(3,959 citation statements)

References 23 publications

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“…Improvements in median OS associated with ICBs versus other therapies have been reported in several cancer types (Table 2), including RCC treated with nivolumab versus the targeted agent everolimus [28], NSCLC treated with either pembrolizumab or atezolizumab versus the chemotherapeutic agent docetaxel [42,57], and UC treated with pembrolizumab versus chemotherapy [46]. However, as novel agents extend patient survival times, it becomes increasingly difficult to conduct long clinical trials in order to measure OS [75,76].…”

Section: Endpoints To Assess Clinical Outcomes Associated With Icbsmentioning

confidence: 99%

“…Some studies investigating ICBs in NSCLC, RCC, HNSCC, and UC have demonstrated increased OS in the absence of a PFS benefit [27,28,31,42,47,57], whereas other trials in melanoma and NSCLC have demonstrated increased OS, as well as ORR and PFS, compared with standard of care (Table 2) [23,43].…”

Section: Endpoints To Assess Clinical Outcomes Associated With Icbsmentioning

confidence: 99%

“…Studies have demonstrated that after initial apparent disease progression, some patients derive clinical benefit from continued administration of immunotherapy [22,38,57,111,[118][119][120][121]. In a phase 3 study (CheckMate 025), 69% of patients with metastatic RCC treated with nivolumab beyond first progression subsequently demonstrated tumor reduction in target lesions, and almost half (48%) had a 30% reduction in tumor burden from baseline [111].…”

Section: Pseudoprogression With Icbsmentioning

confidence: 99%

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Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

et al. 2018

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Immune checkpoint blockers have revolutionized cancer treatment in recent years. These agents are now approved for the treatment of several malignancies, including melanoma, squamous and non-squamous non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, and head and neck squamous cell carcinoma. Studies have demonstrated the significant impact of immunotherapy versus standard of care on patient outcomes, including durable response and extended survival. The use of immunotherapy-based combination therapy has been shown to further extend duration of response and survival. Immunotherapies function through modulation of the immune system, which can lead to immune-mediated adverse events (imAEs). These include a range of dermatologic, gastrointestinal, endocrine, and hepatic toxicities, as well as other less common inflammatory events. ImAEs are typically low grade and manageable when identified early and treated with appropriate measures. Identifying the right patient for the right therapy will become more important as new immunotherapies and immunotherapy-based combinations are approved and costs of cancer care continue to rise.

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Section: Endpoints To Assess Clinical Outcomes Associated With Icbsmentioning

confidence: 99%

Section: Endpoints To Assess Clinical Outcomes Associated With Icbsmentioning

confidence: 99%

Section: Pseudoprogression With Icbsmentioning

confidence: 99%

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Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

et al. 2018

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“…Lack of activity of PD-1/PD-L1-directed agents has also been observed in patients who are never smokers and in patients with EGFR mutation-positive NSCLC [51, 52, 61]. It has been shown that NSCLC patients with tumors that have a high mutational burden have a greater probability of benefit from checkpoint inhibition [62].…”

Section: Post-alk Inhibitor Therapymentioning

confidence: 99%

The Current Landscape of Anaplastic Lymphoma Kinase (ALK) in Non-Small Cell Lung Cancer: Emerging Treatment Paradigms and Future Directions

Qin

Gadgeel

2017

Targ Oncol

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Tumorigenic rearrangements in anaplastic lymphoma kinase (ALK) account for 3–7% of all non-small cell lung cancers (NSCLC). Treatment with targeted tyrosine kinase inhibitors (TKIs) has shown impressive clinical responses. Crizotinib was the first agent approved for front-line therapy of ALK-rearranged NSCLC after it demonstrated superiority to chemotherapy in response rate, duration of response, and progression-free survival. However, eventually all patients progress on crizotinib therapy, with the central nervous system (CNS) being the most common site, which served as the impetus for the development of more potent next-generation ALK inhibitors. Currently, ceritinib, alectinib, and brigatinib are all approved for second-line therapy after progression on or intolerance to crizotinib. Investigations into whether the initiation of a second-generation ALK inhibitor as first-line therapy is the superior treatment paradigm has resulted in the approval of ceritinib as initial therapy. Alectinib has also shown impressive results as front-line therapy, as recently reported in two large randomized studies that compared it to crizotinib. There is a significant need to better understand the drivers of and mechanisms underlying resistance to ALK inhibitors. While specific mutations have been identified, there is currently only limited evidence that the identification of specific mutations should impact selection of the next ALK inhibitor. The best treatment option for patients who become TKI refractory is also unclear, though there is some evidence to suggests that these patients are not responsive to checkpoint inhibitors and may respond better to chemotherapy. Combination therapy with other classes of agents may help to overcome resistance mechanisms and should be investigated further.

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“…Although PD‐1 checkpoint inhibitors, including nivolumab, are now standard treatment for previously treated advanced non‐small cell lung cancer (NSCLC),1, 2, 3 patients with coexisting interstitial lung disease (ILD) were excluded from the original clinical trials for fear of exacerbating this condition 4. Idiopathic pulmonary fibrosis (IPF) is a specific form of ILD characterized by chronic progressive fibrosing interstitial pneumonia of unknown cause and is potentially fatal.…”

Section: Introductionmentioning

confidence: 99%

Durable response to nivolumab in a lung adenocarcinoma patient with idiopathic pulmonary fibrosis

et al. 2018

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The efficacy and safety of immune‐checkpoint inhibitors in non‐small cell lung cancer patients with idiopathic pulmonary fibrosis (IPF) remain unknown. Herein, we describe the case of a 62‐year‐old man with multiple pleural tumors and carcinomatous pleurisy. High‐resolution computed tomography indicated usual interstitial pneumonia, and a respiratory function test revealed a restrictive disorder and decreased diffusion capacity. He was diagnosed with lung adenocarcinoma and IPF. After failure of initial chemotherapy, he was treated with nivolumab and achieved a complete response without any sign of exacerbation of IPF. The response to nivolumab has persisted for > 1 year. This is the first report of a non‐small cell lung cancer patient with IPF who has been treated with immune‐checkpoint inhibitors for such a long period and achieved a sustained response.

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Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial

Abstract: F. Hoffmann-La Roche Ltd, Genentech, Inc.

Cited by 4,036 publications

References 23 publications

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

The Current Landscape of Anaplastic Lymphoma Kinase (ALK) in Non-Small Cell Lung Cancer: Emerging Treatment Paradigms and Future Directions

Durable response to nivolumab in a lung adenocarcinoma patient with idiopathic pulmonary fibrosis

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