In EGFR-mutant advanced NSCLC, immune checkpoint inhibitors do not improve OS over that with docetaxel. Mechanisms of acquired resistance to first-line tyrosine kinase inhibitor therapy should be elucidated to guide selection of second-line treatment for these patients.

Checkpoint inhibitors, compared with docetaxel, are associated with significantly prolong overall survival in second-line therapy in NSCLC. The finding of no overall survival benefit for patients with EGFR mutant tumors suggests that checkpoint inhibitors should be considered only after other effective therapies have been exhausted. The findings of this meta-analysis could also assist in the design and interpretation of future trials and in economic analyses.

In checkpoint-inhibitor trials, ORR correlated poorly with OS. For future phase 2 studies, 6-month PFS rate is recommended as an end point.

CI inhibitors have different toxicity profiles to chemotherapy. These findings are useful for patient counselling and planning of future trials.

Background PD-L1 expression (PD-L1) on tumor cells with or without immune cells is widely reported in clinical trials of PD-1 blockade in metastatic non-small cell lung cancer (NSCLC). Various cutpoints have been studied. Methods We performed a systematic search of MEDLINE, EMBASE and conference proceedings up to December 2019 for randomized and non-randomized clinical trials of anti-PD-1 or anti-PD-L1 monotherapy in metastatic NSCLC. We retrieved data on objective response rate (ORR), 1 year (1yr PFS) and 2 year progression-free survival (2yr PFS), and 2 year (2yr OS) and 3 year overall survival (3yr OS) in various PD-L1 subgroups. Results were pooled and analysed based on different cutpoints, with non-randomized comparisons made to pooled chemotherapy outcomes. Results 9,810 patients in twenty-seven studies were included. In treatment-naïve patients, benefits with PD-1 blockade over chemotherapy were seen in ORR in patients having PD-L1 ≥50%, in 2yr OS for PDL1 ≥1%, and in 1yr PFS, 2yr PFS and 3yr OS for unselected patients. First-line PD-1 blockade compared to chemotherapy demonstrated higher ORR, 2yr PFS and 3yr OS if PD-L1 ≥50%; lower ORR, higher 2yr PFS and similar 3yr OS if PD-L1 1-49%; and lower ORR, similar 1yr PFS and lower 2yr OS if PD-L1 <1%. In previously treated patients, PD-1 blockade demonstrated similar or superior outcomes to chemotherapy in all PD-L1 subgroups. Conclusions PD-L1 should guide the choice of PD-1 blockade versus chemotherapy in treatment-naïve patients. In previously treated patients, PD-1 blockade provides a favourable outcome profile to chemotherapy in all PD-L1 subgroups.

Little has been published on the diagnostic and referral pathway for lung cancer in Australia. This study set out to quantify general practitioner (GP) and lung specialist attendance and diagnostic imaging in the lead-up to a diagnosis of non-small cell lung cancer (NSCLC) and identify common pathways to diagnosis in New South Wales (NSW), Australia. We used linked health data for participants of the 45 and Up Study (a NSW population-based cohort study) diagnosed with NSCLC between 2006 and 2012. Our main outcome measures were GP and specialist attendances, X-rays and computed tomography (CT) scans of the chest and lung cancer-related hospital admissions. Among our study cohort (N = 894), 60% (n = 536) had ≥4 GP attendances in the 3 months prior to diagnosis of NSCLC, 56% (n = 505) had GP-ordered imaging (chest X-ray or CT scan), 39% (N = 349) attended a respiratory physician and 11% (N = 102) attended a cardiothoracic surgeon. The two most common pathways to diagnosis, accounting for one in three people, included GP and lung specialist (respiratory physician or cardiothoracic surgeon) involvement. Overall, 25% of people (n = 223) had an emergency hospital admission. For 14% of people (N = 129), an emergency hospital admission was the only event identified on the pathway to diagnosis. We found little effect of remoteness of residence on access to services. This study identified a substantial proportion of people with NSCLC being diagnosed in an emergency setting. Further research is needed to establish whether there were barriers to the timely diagnosis of these cases.

Multidisciplinary community coordinated care programs are widely adopted to optimise care of chronic disease patients, but there is a need for further evaluation in the setting of COPD. This observational study evaluated 147 patients with severe or very severe COPD who were enrolled in a multidisciplinary community respiratory coordinated care program (RCCP) from 2007 to 2012. Comparison was made of hospitalisation rates and length of stay for 12 months prior to joining the program, and the first 12 months after joining the program. This data was used to inform a cost analysis. Enrolment into RCCP halved the annual hospital admission rate from 1.18 to 0.57 admissions per year (relative risk reduction 51.4%, p < 0.001), and annual total length of stay was reduced from 8.06 to 3.59 days per patient per year (p < 0.001). Hospital admissions were reduced from 5.05 days to 2.00 days (p < 0.001). Accounting for the program's costs, these changes resulted in a $US 906.94 ($AUD 972.80) cost saving per patient per year. A RCCP program can reduce patient hospitalisation and overall costs in the COPD setting.

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