Ann Robinson’s research reviews—6 October 2022

Checkpoint inhibition: hopeful in lung cancer…

Extensive stage small cell lung cancer (SCLC) that has spread throughout one or both lungs, or to distant sites, has a terrible prognosis with five year survival rates of only 2-3%. Standard treatment is with chemotherapy using platinum-etoposide combinations. But clearly there’s a pressing need for better options. The novel immunotherapy drug serplulimab acts as a checkpoint inhibitor by blocking programmed cell death-1 protein (PD-1), which tries to stop the body’s immune system from attacking cancer cells. In this randomised trial of 585 patients with extensive stage SCLC who had never had any systemic therapy, serplulimab plus chemotherapy was more effective than chemotherapy alone in prolonging survival (15.4 months v 10.9 months). Secondary outcomes—including progression-free survival, objective response rate, and duration of response—all seemed to be better in the serplulimab group, and the rate of adverse events was similar in both groups. We still need to know how serplulimab compares with other immunotherapy drugs such as atezolizumab or durvalumab when added to standard chemotherapy, which platinum drug to use (carboplatin or cisplatin), and whether serplulimab remains effective and safe in the longer term.

JAMA doi:10.1001/jama.2022.16464

… disappointing in kidney cancer

Surgery (partial or radical nephrectomy) can be curative in renal cell carcinoma (RCC), but the cancer recurs in 20-40% of cases, and then options include immunotherapy drugs such as atezolizumab, a checkpoint inhibitor that binds to programmed cell death-ligand 1 (PD-L1). However, results were disappointing in a multicentre study of adjuvant immunotherapy for RCC in people at increased risk of recurrence. There was no evidence of clinical benefit in disease-free survival (57 v 49 months) or overall survival at 3 years (around 90% in both groups) with adjuvant atezolizumab compared with placebo in patients with high-risk localised or fully resected RCC. It’s possible that future work will use genomics or biomarkers to find individuals who might benefit from adjuvant atezolizumab after nephrectomy.

Lancet doi:10.1016/S0140-6736(22)01658-0

A time to die

This may seem macabre, but it would be helpful for us to be able to let patients and families know how long they’ve got left to live. I’d certainly welcome an informed prediction before I draft an advanced care plan, decide whether to attend cancer screening tests, or start medication to prevent long term complications that I may not live long enough to develop. But there’s no point in hazarding a guess; clinicians need models that generate reliable and accurate predictions.

This US study used two cohorts of people with probable dementia who were living in the community (1998-2016 and 2011-19) to develop and externally validate a mortality prediction model using clinical predictors such as demographics, health factors, functional measures, and chronic conditions. The participants’ mean age was 82 years, and 81% had died by the end of the four year follow-up period. The model provided accurate mortality risk predictions across a 10 year time frame. Admittedly, the diagnosis and classification of dementia in this study were uneven, but the model seemed to perform well compared with previous models. Longer follow up in other cohorts could make this model even more robust.

JAMA Intern Med doi:10.1001/jamainternmed.2022.4326

Smokers past and present still get puffed

Around a quarter of people who have ever smoked, including those who have quit, say that they get breathless on exertion despite normal lung function tests. It’s tempting to prescribe bronchodilators in these cases, but this randomised study of 535 former or current smokers with normal lung function tests on spirometry found that dual long-acting bronchodilators didn’t help respiratory symptoms compared with placebo (mean change in predicted FEV₁ 2.48 v −0.09 percentage points). A significant flaw in the study is that participants may have had coughs, wheeze, or breathlessness due to non-respiratory problems such as heart disease, and their inclusion may have led to an underestimate of the bronchodilator effect. It’s also possible that inhaled glucocorticoids, azithromycin, or pulmonary rehabilitation may help respiratory symptoms in this group. Further studies are needed, especially since former smokers who remain breathless may become disheartened and take up smoking again.

N Engl J Med doi:10.1056/NEJMoa2204752

Monkeypox vaccine highly effective

There have been nearly 60 000 recorded cases of monkeypox (MPX) worldwide in the current outbreak. The MVA-BN vaccine, developed as a smallpox vaccine, is licensed for MPX prevention, and the immunogenicity data look great, with 100% response rate at two weeks after two doses. Some centres may be tempted to give a single dose only as vaccine supplies are low. However, this small, single centre study of people who tested positive for MPX at least one day after getting the vaccine found that most (69/90) did so within the first two weeks of the vaccine, before it was likely to have become fully effective. Some of these people may have been incubating the virus before they got the vaccine as the incubation period is 3-17 days. There were also two breakthrough cases more than three weeks after the second dose. Over a third of the post-vaccination cases were among men living with HIV, although the vast majority were virologically suppressed. The trial results, published in a research letter, need to be treated with caution because of the small numbers, single test site, and inconsistent follow-up. Larger studies are needed to determine the effectiveness of the vaccine and how long its effect lasts. As with covid, the jab is no license to abandon behavioural measures to reduce transmission. In the case of monkeypox, that means hand washing and avoiding close contact with infected people.

JAMA doi:10.1001/jama.2022.18320