Durvalumab Consolidation Therapy Shows Promise in Elderly Patients With Stage III NSCLC

Australian investigators have determined consolidation durvalumab to be as effective among a patient population 70 years and older who has unresectable stage III non–small cell lung cancer (NSCLC) as in those who are younger than 70 years, according to new findings published in Journal of Geriatric Oncology.¹

The setting for the consolidation treatment with the anti–PD-L1 antibody—treatment administered following a cancer’s disappearance after initial treatment²—was post platinum-based chemoradiotherapy (CRT). These investigators explained that they researched the treatment in this setting because older patients had been underrepresented in the PACIFIC trial, and results trended toward poorer outcomes (worse survival and greater toxicity) for patients 70 years and older. They sought a more comprehensive understanding of durvalumab’s safety and efficacy in these patients.

Their study population consisted of 65 patients 70 years and older and 87 patients younger than 70 years. The median overall age was 67 (range, 46-84) years, and 63.2% were male patients. An ECOG performance status (PS) of 0 (indicating the patient remains full active) was more common in the younger group (61%) vs the older group (46.6%), and an ECOG PS of 1, more common in the older vs the younger group (50.8% vs 33.3%). Rates of baseline chronic obstructive pulmonary disease (COPD) and cardiovascular disease were common in the older patients vs the younger patients, at 46.1% and 67.7% vs 23% and 48.3%, respectively, and current tobacco use was more common among the younger patients (79.3% vs 52.3%) and former and never-use statuses more common in the older patients (29.2% vs 10.3% and 18.5% vs 10.3%, respectively.

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“Lung cancer incidence increases with age, with the media age at diagnosis in Australia being 71 years old,” the authors wrote. “Real-world data can inform clinicians about outcomes for patients who are underrepresented in randomized controlled trials, allowing for further generalizability of the results.”

Their primary outcome was 2-year overall survival (OS), which was the time from durvalumab initiation to death from any cause. Secondary outcomes were progression-free survival, treatment-related toxicity, treatment-related death, and toxicity-related treatment discontinuation.

The 152 patients included in this multicenter retrospective cohort study all had at least 1 cycle of durvalumab, but median overall administrations were 22, and this did not vay by age. The median follow-up was 26 (range, 4.1-56.7) months. Patients in the older-age group were more likely to have received carboplatin-based chemotherapy (P < .001).

Rates of treatment delay (30.8% vs 34.5%; P = .61), treatment stoppage due to toxicity (24.6% vs 16.1%; P = .23), or disease progression (30.8% vs 29.9%; P = .23) did not vary between the older and younger groups, respectively.

Median overall 2-year OS was 70.6% (95% CI, 63.2% vs 78.1%), and median OS was not reached. However, the 2-year OS was 65.2% (95% CI, 53.4%-77%) in the older patients vs 74.8% (95% CI, 65.4%-84.2%) in the younger cohort. Older age, Charlson Comorbidity Index (CCI) score of 5 or higher, and EGFR mutations were associated with OS (P < .10).

The median overall PFS and PFS among the younger population were the same, at 30.3 months, while among the older patients, this was 26.7 months (HR, 1.46; 95% CI, 0.80-2.65; P = .22); also in the latter group, a potential link was seen between EGFR mutations and previous tobacco use and worse PFS.

When toxicity was gauged, 94.7% of all patients had an adverse event (AE) during CRT, with 25.7% of these being grade 3 or 4; this toxicity grade was not linked to older age or ECOG PS, but it was linked to longer time to durvalumab initiation (P = .049). Among the 77% of patients who had an AE during durvalumab consolidation, 14.5% were grade 3 or 4; significant differences in toxicity were not seen between the older and younger patients. Grade 3 or 4 AEs were linked to a CCI score of 5 or higher (P = .01) and COPD (P = .07) on univariate analysis, and the CCI score of 5 or higher retained its significance on multivariate analysis (P = .022).

The authors note that their study is not the only one to have evaluated the treatment regimen set out in the PACIFIC trial, and that despite their small sizes or limited study sites, these analyses still add valuable findings for groups underrepresented in PACIFIC. Speaking to their study in particular, while admitting that there were more non–NSCLC-related deaths among their older patients, they emphasized that this may suggest age to not be a determinant of treatment tolerance of durvalumab; that instead, comorbidity burden may hold more influence in this regard.

“The increasing recognition of frailty as a prognostic entity in NSCLC should prompt clinicians to undertake additional assessment when determining appropriate treatment for older patients in the future,” they concluded. “As treatment options for early lung cancer become increasingly complex, oncologists should bear these factors in mind when assessing the risk of harm and likelihood of benefit in older patients.”

References

1. Stevens S, Nindra U, Shahnam A, et al. Real world efficacy and toxicity of consolidation durvalumab following chemoradiotherapy in older Australian patients with unresectable stage III non-small cell lung cancer. J Geriatr Oncol. 2024;15(2):101705. doi:10.1016/j.jgo.2024.101705
2. Consolidation therapy. National Cancer Institute. Accessed January 12, 2024. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/consolidation-therapy