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ICI Therapy Outcomes Reported For Older And Trial-Ineligible Cancer Patients

Patients aged over 80 years may benefit from immune checkpoint inhibitor therapy but the efficacy in patients with a poor performance status or organ dysfunction is less clear
05 Nov 2021
Cancer in Special Situations;  Geriatric Oncology;  Immunotherapy

By Lynda Williams, Senior medwireNews Reporter 

 

medwireNews: Older age should not preclude immune checkpoint inhibitor (ICI) use in cancer patients but individuals with a poor performance status or organ dysfunction may not benefit from ICI therapy, suggest the results of two studies published in JAMA Oncology. 

Abdul Rafeh Naqash, from the University of Oklahoma in Oklahoma City, USA, and co-workers reviewed data from 928 patients from the USA and Europe who were aged a median of 83.0 years at time of single-agent ICI initiation between 2010 and 2019, with 909 patients aged 80 years or older at this point. 

The patients were given a PD-1 inhibitor (86.9%), a PD-L1 inhibitor (8.5%) or a CTLA-4 inhibitor (4.6%) for a range of tumours, most commonly non-small-cell lung cancer (NSCLC; 37.2%), melanoma (35.5%) and genitourinary (GU) cancers (16.5%). 

Among patients whose response to treatment was evaluated, the objective response rate was 32.2% for NSCLC patients, including 34.5% for those aged less than 85 years and 25.7% for older individuals. The corresponding rates for melanoma patients were 39.3%, 35.8% and 45.5%, while for GU cancer patients, the rates were 26.2%, 29.8% and 19.0%.  

Median progression-free survival (PFS) in the overall NSCLC, melanoma and GU cancer groups was 6.7, 11.1 and 6.0 months, respectively, while median overall survival (OS) was 10.9, 30.0 and 15.0 months. 

Multivariate analysis showed that increasing age was not significantly predictive of PFS or OS in the NSCLC, melanoma and GU cancer patient groups, and safety analysis found “comparable rates” of any-grade and grade 3–4 immune-related adverse events in patients aged less than 85 years, 85–89 years and 90 years or older. 

However, patients aged 90 years and older were significantly more likely than their younger counterparts to discontinue therapy following immune-related adverse events (30.9 vs 15.1%), indicating a “lower tolerance for toxic effects” in this group that may be “potentially driven by patient preference, declining functional status, or physician risk aversion.” 

Abdul Rafeh Naqash et al conclude: “Although a more precise understanding of age-related biology is warranted, findings of this study suggest that advanced age in itself should not preclude ICI therapy.” 

 

For the second study, Ravi Parikh, from the University of Pennsylvania in Philadelphia, USA, and colleagues reviewed the outcomes of 34,131 patients who began first-line systemic therapy between 2014 and 2019, 27.3% of whom were ineligible for participation in a clinic trial because of an ECOG performance status of 2 or higher, or liver or kidney dysfunction. 

The patients had newly diagnosed metastatic or recurrent NSCLC or urothelial cell, renal cell or hepatocellular carcinoma unsuitable for targeted therapy, were aged a median of 70 years, and were mainly White (69%) and male (58%). 

Over the study period, ICI monotherapy use increased among both the trial-eligible patients (from 0.1% to 19.4%) and trial-ineligible patients (from 0.0% to 30.2%).  

Patients who were ineligible for clinical trials were significantly more likely to receive ICI monotherapy than non-ICI therapy (inverse probability-weighted [IPW]-adjusted odds ratio [aOR]=1.80); this was true also for subgroups of patients with urothelial cell carcinoma (aOR=2.48) and NSCLC (aOR=1.95), whereas there was no significant association among renal cell and hepatocellular carcinoma patients. 

Furthermore, there was no significant difference in OS after 12 or 36 months among trial-ineligible patients who received ICI monotherapy, ICI combination therapy or non-ICI therapy.  

And further analysis indicated that ICI monotherapy or combination use in trial-ineligible patients was associated with early harm in the first 6 months compared with non-ICI therapy, but a possible late benefit among patients who survived beyond 6 months, with IPW-adjusted hazard ratios for death of 1.14–1.19 and 0.80–1.00, respectively. 

The researchers note that shorter survival before and after 6 months with ICI combination therapy was “particularly notable” for hepatocellular carcinoma patients, perhaps from exacerbation of life-threatening adverse events associated with both treatment classes in patients with poor performance status and organ dysfunction. 

“[O]ur findings argue for cautious use of ICI combination therapy in trial-ineligible patients”, say Ravi Parikh and co-authors, but add that their study findings for ICI monotherapy and combination therapy “must be validated in prospective phase 3 studies before changing clinical practice.” 

Nevertheless, they emphasize: “Clinicians who care for patients with poor [performance status] or organ dysfunction should be cautious about ICI use and carefully weigh expected survival gains against the potential for early mortality and adverse effects.” 

 

References 

Nebhan CA, Cortellini A, Ma W, et al. Clinical outcomes and toxic effects of single-agent immune checkpoint inhibitors among patients aged 80 years or older with cancer. A multicenter international cohort study. JAMA Oncol; Advance online publication 4 November 2021. doi:10.1001/jamaoncol.2021.4960  

Parikh RB, Min EJ, Wileyto EP, et al. Uptake and survival outcomes following immune checkpoint inhibitor therapy among trial-ineligible patients with advanced solid cancers. JAMA Oncol; Advance online publication 4 November 2021. doi:10.1001/jamaoncol.2021.4971 

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2021 Springer Healthcare part of the Springer Nature group

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