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The IMpower150 trial showed significant improvements in progression-free and overall survival with atezolizumab plus bevacizumab plus carboplatin plus paclitaxel (ABCP) versus the standard-of-care bevacizumab plus carboplatin plus paclitaxel (BCP) in chemotherapy-naive patients with non-squamous non-small-cell lung cancer. Here, we report the efficacy of ABCP or atezolizumab plus carboplatin plus paclitaxel (ACP) versus BCP in key patient subgroups. IMpower150 was a randomised, open-label, phase 3 study done at 240 academic medical centres and community oncology practices across 26 countries worldwide. Patients with chemotherapy-naive metastatic non-small-cell lung cancer were randomly assigned (1:1:1) to receive ABCP, ACP, or BCP every three weeks. The co-primary endpoints were overall survival and investigator-assessed progression-free survival in intention-to-treat wild-type patients (patients with epidermal growth factor receptor [ EGFR ] or anaplastic lymphoma kinase [ ALK ] genetic alterations were excluded). Efficacy was assessed in key subgroups within the intention-to-treat population, including patients with EGFR mutations (both sensitising and non-sensitising; EGFR -positive) previously treated with one or more tyrosine kinase inhibitors and patients with baseline liver metastases. Overall survival in the intention-to-treat population was included among secondary efficacy endpoints. Exploratory endpoints included the proportion of patients achieving an objective response in the intention-to-treat population, including EGFR -positive patients and patients with baseline liver metastases. Data are reported as per the Jan 22, 2018, data cutoff date, at which the number of coprimary prespecified overall survival events was met in the ABCP versus BCP groups. This trial is registered with ClinicalTrials.gov , number NCT02366143 , and is ongoing. Between March 31, 2015, and Dec 30, 2016, 1202 patients were enrolled. 400 patients were randomly assigned to ABCP, 402 to ACP, and 400 to BCP. In EGFR -positive patients (124 of 1202), median overall survival was not estimable (NE; 95% CI 17·0–NE) with ABCP (34 of 400) and 18·7 months (95% CI 13·4–NE) with BCP (45 of 400; hazard ratio [HR] 0·61 [95% CI 0·29–1·28]). Improved overall survival with ABCP versus BCP was observed in patients with sensitising EGFR mutations (median overall survival NE [95% CI NE–NE] with ABCP [26 of 400] vs 17·5 months [95% CI 11·7–NE] with BCP [32 of 400]; HR 0·31 [95% CI 0·11–0·83]) and in the intention-to-treat population (19·8 months [17·4–24·2] vs 14·9 months [13·4–17·1]; HR 0·76 [0·63–0·93]). Improved median overall survival with ABCP versus BCP was seen in patients with baseline liver metastases (13·3 months [11·6–NE] with ABCP [52 of 400] vs 9·4 months [7·9–11·7] with BCP [57 of 400]; HR 0·52 [0·33–0·82]). Median overall survival was 21·4 months (95% CI 13·8–NE) with ACP versus 18·7 months (95% CI 13·4–NE) with BCP in EGFR -positive patients (HR 0·93 [95% CI 0·51–1·68]). No overall survival benefit was seen with ACP versus BCP in patients with sensitising EGFR mutations (HR 0·90 [95% CI 0·47–1·74]), in the intention-to-treat population (HR 0·85 [0·71–1·03]), or in patients with baseline liver metastases (HR 0·87 [0·57–1·32]). In the intention-to-treat safety-evaluable population, grade 3–4 treatment-related events occurred in 223 (57%) patients in the ABCP group, in 172 (43%) in the ACP group, and in 191 (49%) in the BCP group; 11 (3%) grade 5 adverse events occurred in the ABCP group, as did four (1%) in the ACP group, and nine (2%) in the BCP group. Improved survival was noted for patients treated with ABCP compared with those given BCP in the intention-to-treat population, and in patients with baseline liver metastases. The overall survival signal in the subgroup of patients with EGFR sensitising mutations warrants further study. F. Hoffmann-La Roche, Genentech. [ABSTRACT FROM AUTHOR]

Summary The MAP-kinase pathway, consisting of the kinases RAS, RAF, MEK, and ERK, is crucial for cell proliferation, inhibition of apoptosis, and migration of cells. Direct inhibition of RAS is not yet possible, whereas inhibition of RAF is already established in malignant melanoma and under investigation in non-small-cell lung cancer (NSCLC). Due to their structure and function, the MEK proteins are attractive targets for cancer therapy and are also under investigation in NSCLC. We discuss strategies of targeting the RAS-RAF-MEK-ERK pathway with emphasis on MEK inhibition, either alone or in combination with other targets or conventional chemotherapy. [ABSTRACT FROM AUTHOR]

Non-small-cell lung cancer is one of the leading causes of deaths from cancer worldwide. Therefore, improvements in diagnostics and treatments are urgently needed. In this review, we will discuss the evolution of lung cancer staging towards more non-invasive, endoscopy-based, and image-based methods, and the development of stage-adapted treatment. A special focus will be placed on the role of novel surgical approaches and modern radiotherapy strategies for early stages of disease, the effect of multimodal treatment in locally advanced disease, and ongoing developments in the treatment of patients with metastatic disease. In particular, we will include an emphasis on targeted therapies, which are based on the assumption that a treatable driver mutation or gene rearrangement is present within the tumour. Finally, the position of lung cancer treatment on the pathway to personalised therapy will be discussed. [ABSTRACT FROM AUTHOR]

The article reports on research studies on the use of immunotherapy for the management of lung cancer.

Despite immunotherapy advancements for patients with advanced or metastatic non-small-cell lung cancer (NSCLC), pivotal first-line trials were limited to patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1 and a median age of 65 years or younger. We aimed to compare the efficacy and safety of first-line atezolizumab monotherapy with single-agent chemotherapy in patients ineligible for platinum-based chemotherapy. This trial was a phase 3, open-label, randomised controlled study conducted at 91 sites in 23 countries across Asia, Europe, North America, and South America. Eligible patients had stage IIIB or IV NSCLC in whom platinum-doublet chemotherapy was deemed unsuitable by the investigator due to an ECOG PS 2 or 3, or alternatively, being 70 years or older with an ECOG PS 0–1 with substantial comorbidities or contraindications for platinum-doublet chemotherapy. Patients were randomised 2:1 by permuted-block randomisation (block size of six) to receive 1200 mg of atezolizumab given intravenously every 3 weeks or single-agent chemotherapy (vinorelbine [oral or intravenous] or gemcitabine [intravenous]; dosing per local label) at 3-weekly or 4-weekly cycles. The primary endpoint was overall survival assessed in the intention-to-treat population. Safety analyses were conducted in the safety-evaluable population, which included all randomised patients who received any amount of atezolizumab or chemotherapy. This trial is registered with ClinicalTrials.gov , NCT03191786. Between Sept 11, 2017, and Sept 23, 2019, 453 patients were enrolled and randomised to receive atezolizumab (n=302) or chemotherapy (n=151). Atezolizumab improved overall survival compared with chemotherapy (median overall survival 10·3 months [95% CI 9·4–11·9] vs 9·2 months [5·9–11·2]; stratified hazard ratio 0·78 [0·63–0·97], p=0·028), with a 2-year survival rate of 24% (95% CI 19·3–29·4) with atezolizumab compared with 12% (6·7–18·0) with chemotherapy. Compared with chemotherapy, atezolizumab was associated with stabilisation or improvement of patient-reported health-related quality-of-life functioning scales and symptoms and fewer grade 3–4 treatment-related adverse events (49 [16%] of 300 vs 49 [33%] of 147) and treatment-related deaths (three [1%] vs four [3%]). First-line treatment with atezolizumab monotherapy was associated with improved overall survival, a doubling of the 2-year survival rate, maintenance of quality of life, and a favourable safety profile compared with single-agent chemotherapy. These data support atezolizumab monotherapy as a potential first-line treatment option for patients with advanced NSCLC who are ineligible for platinum-based chemotherapy. F Hoffmann-La Roche and Genentech Inc, a member of the Roche group. [ABSTRACT FROM AUTHOR]

This article discusses research into the efficacy of the medications gefitinib and docetaxel in the treatment of metastatic non-small-cell lung cancer in patients who had already undergone chemotherapy. This open-label phase three study compared survival rates among patients administered with one of the medications. The possible interaction between these medications and patients with the high-epidermal growth factor receptor gene-copy number. The study established the non-inferiority of gefitinib.