Nabilone is an adequate and safe therapeutic option to aid in the treatment of patients diagnosed with anorexia. Larger trials are necessary in order to draw robust conclusions in regard to its efficacy in lung cancer patients.

IMPORTANCE Metformin hydrochloride is emerging as a repurposed anticancer drug. Preclinical and retrospective studies have shown that it improves outcomes across a wide variety of neoplasms, including lung cancer. Particularly, evidence is accumulating regarding the synergistic association between metformin and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). OBJECTIVE To assess the progression-free survival (PFS) in patients with advanced lung adenocarcinoma who received treatment with EGFR-TKIs plus metformin compared with those who received EGFR-TKIs alone. DESIGN, SETTING, AND PARTICIPANTS Open-label, randomized, phase 2 trial conducted at the Instituto Nacional de Cancerología (INCan), Mexico City, Mexico. Eligible patients were 18 years or older, had histologically confirmed stage IIIB-IV lung adenocarcinoma with an activating EGFR mutation. INTERVENTIONS Patients were randomly allocated to receive EGFR-TKIs (erlotinib hydrochloride, afatinib dimaleate, or gefitinib at standard dosage) plus metformin hydrochloride (500 mg twice a day) or EGFR-TKIs alone. Treatment was continued until occurrence of intolerable toxic effects or withdrawal of consent. MAIN OUTCOMES AND MEASURES The primary outcome was PFS in the intent-to-treat population. Secondary outcomes included objective response rate, disease control rate, overall survival (OS), and safety.

Because of socioeconomic factors, many patients with advanced non-small cell lung cancer (NSCLC) do not receive immunotherapy in the first-line setting. It is unknown if the combination of immunotherapy with chemotherapy can provide clinical benefits in immunotherapy-naive patients with disease progression after treatment with platinum-based chemotherapy.OBJECTIVE To evaluate the safety and efficacy of the combination of pembrolizumab plus docetaxel in patients with previously treated advanced NSCLC following platinum-based chemotherapy regardless of EGFR variants or programmed cell death ligand 1 status. DESIGN, SETTING, AND PARTICIPANTSThe Pembrolizumab Plus Docetaxel for Advanced Non-Small Cell Lung Cancer (PROLUNG) trial randomized 78 patients with histologically confirmed advanced NSCLC in a 1:1 ratio to receive either pembrolizumab plus docetaxel or docetaxel alone from December 2016 through May 2019. INTERVENTIONSThe experimental arm received docetaxel on day 1 (75 mg/m 2 ) plus pembrolizumab on day 8 (200 mg) every 3 weeks for up to 6 cycles followed by pembrolizumab maintenance until progression or unacceptable toxic effects. The control arm received docetaxel monotherapy. MAIN OUTCOMES AND MEASURESThe primary end point was overall response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival, and safety. RESULTS Among 78 recruited patients, 32 (41%) were men, 34 (44%) were never smokers, and 25 (32%) had an EGFR/ALK alteration. Forty patients were allocated to receive pembrolizumab plus docetaxel, and 38 were allocated to receive docetaxel. A statistically significant difference in ORR, assessed by an independent reviewer, was found in patients receiving pembrolizumab plus docetaxel vs patients receiving docetaxel (42.5% vs 15.8%; odds ratio, 3.94; 95% CI, 1.34-11.54; P = .01). Patients without EGFR variations had a considerable difference in ORR of 35.7% vs 12.0% (P = .06), whereas patients with EGFR variations had an ORR of 58.3% vs 23.1% (P = .14). Overall, PFS was longer in patients who received pembrolizumab plus docetaxel (9.5 months; 95% CI, 4.2-not reached) than in patients who received docetaxel (3.9 months; 95% CI, 3.2-5.7) (hazard ratio, 0.24; 95% CI, 0.13-0.46; P < .001). For patients without variations, PFS was 9.5 months (95% CI, 3.9-not reached) vs 4.1 months (95% CI, 3.5-5.3) (P < .001), whereas in patients with EGFR variations, PFS was 6.8 months (95% CI, 6.2-not reached) vs 3.5 months (95% CI, 2.3-6.2) (P = .04). In terms of safety, 23% (9 of 40) vs 5% (2 of 38) of patients experienced grade 1 to 2 pneumonitis in the pembrolizumab plus docetaxel and docetaxel arms, respectively (P = .03), while 28% (11 of 40) vs 3% (1 of 38) experienced any-grade hypothyroidism (P = .002). No new safety signals were identified. CONCLUSIONS AND RELEVANCEIn this phase 2 study, the combination of pembrolizumab plus docetaxel was well tolerated and substantially improved ORR and PFS in patients with advanced NSCLC who had previous progression after platinum-based chem...

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Background: To compare survival outcomes of patients with advanced or metastatic non-small cell lung cancer (NSCLC) who received immunotherapy as first-, second-or beyond line, versus matched patients receiving standard chemotherapy with special characterization of hyperprogressors. Methods: A retrospective cohort study of 296 patients with unresectable/metastatic NSCLC treated with either, first-, second-, third-or fourth-line of immunotherapy was conducted. A matched comparison with a historical cohort of first-line chemotherapy and a random forest tree analysis to characterize hyperprogressors was conducted. Results: Median age was 64 years (range 34-90), 40.2% of patients were female. A total of 91.2% of patients had an Eastern Cooperative Oncology Group (ECOG) performance score ≤ 1. Immunotherapy as first-line was given to 39 patients (13.7%), second-line to 140 (48.8%), and as third-line and beyond to 108 (37.6%). Median overall survival was 12.7 months (95% CI 9.67-14 months) and progression-free survival (PFS) of 4.27 months (95% CI 3.97-5.0). Factors associated with increased survival included treatment with immunotherapy as first-line (P < 0.001), type of response (P < 0.001) and PD-L1 status (P = 0.0039). Compared with the historical cohort, immunotherapy proved to be superior in terms of OS (P = 0.05) but not PFS (P = 0.2). A total of 44 hyperprogressors were documented (19.8%,.1%]). Leukocyte count over 5.300 cells/dL was present in both hyperprogressors and long-term responders. Conclusions: Patients who receive immune-checkpoint inhibitors as part of their treatment for NSCLC have better overall survival (OS) compared with matched patients treated with standard chemotherapy, regardless of the line of treatment.

Introduction: Immune checkpoint inhibitor-related pneumonitis (ICIP) is a potentially life threatening immune-related adverse event (irAE), especially in non-small cell lung cancer (NSCLC) patients. Currently, the potential for increased irAE in patients who receive radiotherapy is scarcely known, although a connection between antitumor immune responses and irAEs has been suggested. In this study, we evaluated the development of ICIP in non-small cell lung cancer patients with prior radiotherapy, treated with immunotherapy in the second-line. Methods: In this retrospective trial, we included patients treated with second-line immunotherapy at the National Cancer Institute in Mexico City from February 2015 to February 2018. Clinical, radiological and treatment variables were evaluated according to the presence of ICIP as defined by the Common Terminology Criteria for Adverse Events (4.0) in patients with or without a previous (≥months) history of radiotherapy. Results: Among 101 NSCLC patients who received treatment with ICIs, 22 patients (21.8%) were diagnosed with ICIP, of which 73% (16/22) had a history of radiotherapy (OR 6.04, 95% CI 2.03−18.0, p < 0.001). Median progression free survival and overall survival were similar in patients who developed ICIP compared with those who did not, however, patients who presented grade ≥ 2 ICIP had an increased risk of mortality (HR 2.54, 95% CI 1.20−5.34, p = 0.014). Conclusion: In this real-world cohort of NSCLC patients treated with ICI, the history of prior radiotherapy was associated with increased risk for ICIP development. Unlike other irAEs, grade ≥ 2 ICIP is an independent prognostic factor for decreased survival in NSCLC patients.

Objectives: Lung cancer is a heterogeneous disease. Presentation and prognosis are known to vary according to several factors, such as genetic and demographic characteristics. Small-cell lung cancer incidence is increasing in never-smokers. However, the disease phenotype in this population is different compared with patients who have a smoking history. Material and Methods: To further investigate the clinical and genetic characteristics of this patient subgroup, a cohort of small cell lung cancer patients was divided into smokers ( n = 10) and never/ever-smokers ( n = 10). A somatic mutation profile was obtained using a comprehensive NGS assay. Clinical outcomes were compared using the Kaplan-Meier method and Cox proportional models. Results: Median age was 63 years (46–81), 40% were men, and 90% had extended disease. Smoker patients had significantly more cerebral metastases ( p = 0.04) and were older ( p = 0.03) compared to their non-smoker counterparts. For never/ever smokers, the main genetic mutations were TP53 (80%), RB1 (40%), CYLD (30%), and EGFR (30%). Smoker patients had more RB1 (80%, p = 0.04), CDKN2A (30%, p = 0.05), and CEBPA (30%, p = 0.05) mutations. Response rates to first-line therapy with etoposide plus cisplatin/carboplatin were 50% in smokers and 90% in never/ever smokers ( p = 0.141). Median overall survival was significantly longer in never smokers compared with smokers (29.1 months [23.5–34.6] vs. 17.3 months [4.8–29.7]; p = 0.0054). Never/ever smoking history (HR 0.543, 95% CI 0.41–0.80), limited-stage disease (HR 0.56, 95% CI 0.40–0.91) and response to first-line platinum-based chemotherapy (HR 0.63, 95% CI 0.60–0.92) were independently associated with good prognosis. Conclusion: Our data supports that never/ever smoker patients with small-cell lung cancer have better prognosis compared to their smoker counterparts. Further, patients with never/ever smoking history who present with small-cell lung cancer have a different mutation profile compared with smokers, including a high frequency of EGFR, MET , and SMAD4 mutations. Further studies are required to assess whether the differential mutation profile is a consequence of a diverse pathological mechanism for disease onset.

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