Lung cancer

ICI inhibitors in the real world: poorer outcomes for most patients

Survival outcomes of real world, advanced lung cancer patients receiving immunotherapy differ depending on whether or not patients would have met eligibility criteria for relevant RCTs.

The findings have clinical implications including how to source better evidence on which to base clinical discussions.

Speaking at the MOGA 2022 ASM, Dr Monica Tang presented the results of a sub-study of the Embedding Research (and evidence) in Cancer Healthcare (EnRICH) study in metropolitan and regional NSW.

The current study comprised 216 NSCLC patients diagnosed with de novo stage IV disease between December 2016 and February 2021 and receiving at least one dose of immunotherapy.

The median age was 69.5 years, 40% were female and 44% met all eligibility criteria for relevant landmark, phase three immunotherapy clinical trials. She noted immunotherapy moved from mostly second line therapy to first line therapy across the study period.

Dr Tang said the median overall survival (OS) was 10.2 months for all patients receiving first line immunotherapy, 13.1 months for those assessed as trial eligible, and 8.8 months for those who were not trial eligible.

The median OS for those treated in the second line setting was 5.4 months, 7.5 months for trial-eligible patients and 3.4 months for non-trial eligible patients.

“We found that OS was significantly associated with whether or not a patient would be considered trial-eligible with trial-eligible patients having 35% longer OS than those who were not trial-eligible.”

The study found grade 3-5 adverse events including cardiovascular toxicities, cytopaenias and GI toxicities were similar in both patients considered trial-eligible and those who were not – but lower in the first line setting (41%) than in the second line setting (58%).

Dr Tang Median said median OS in real world patients with advanced NSCLC receiving ICI inhibitors was already shorter in routine clinical care than reported in landmark RCTs.

Median OS for first line therapy in the study was 10 months compared to 16-30 months reported in RCTs; in second line therapy 5 months compared 9-14 months in clinical trials.

“I think that the difference between median OS in a real world population compared to what is reported in clinical trials has important ramifications in clinic when trying to prognosticate for patients or when discussing the potential benefits of treatment.”

“In addition the poorer survival of real world patients who are not trial-eligible may raise questions about the generalisability of clinical trials results to these patients.”

Speaking to the limbic after her presentation, Dr Tang said findings were not entirely unexpected.

“It’s intuitive that non-trial eligible patients do have poor prognosis but the key message is that we don’t have good quality prospective data about what is actually the best treatment for them because they are excluded from so many trials – the traditional chemotherapy trials, the immunotherapy trials.”

“Most clinicians do their best by extrapolating from existing data but in an ideal world we would be able to take these poor prognosis patients with comorbidities or who are older and see what is best for them.”

“Obviously patients who aren’t trial eligible, those with poor performance status, lots of comorbidities, poor organ dysfunction, we know they are a poor prognostic group. They will do poorly regardless of what we give them.”

She said it was however possible to supplement the RCT data with that from studies such as EnRICH, routinely collected data from the EHR or health administrative data.

“In Australia we have such a great universal health system, we’ve got cancer registry data, we know how long patients survive and we can determine what they are dispensed through the PBS. If we could somehow use all of the different data sources …we could come up with a better evidence base.”

On the issue of immunotherapy adverse events she said there had been a lot of excitement and hype about the potential for fewer adverse events – something which had to be managed in clinical discussion.

“Adverse event rates reported in immunotherapy trials are not much better than those reported in chemotherapy trials. I think there is that perception in patients and some clinicians as well that it is somehow more tolerable and benign.”

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