Durvalumab Underutilization Highlights Gaps in NSCLC Treatment Strategies

With disappointing findings on the ability of consolidation durvalumab to produce positive outcomes among patients being treated for unresectable stage III non–small cell lung cancer (NSCLC), investigators of a new study published in PLoS ONE are saying that treatment strategies that involve the immune checkpoint inhibitor need to be refined due to unmet medical needs.¹

The historic standard of care for unresectable stage III NSCLC was platinum-based chemotherapy and concurrent radiotherapy (cCRT) and surveillance, the authors note.² Yet, approximately half of patients go on to develop distant metastases,³ and the 5-year overall survival rate is a dismal 37%.⁴ Noting the difficulty of treating disease in these patients, they highlight how their findings show the regimen is underutilized despite known benefits, with 4 of 10 patients eligible for consolidation durvalumab not receiving it.¹

Durvalumab, an immune checkpoint inhibitor (ICI), was first approved for use in the US as consolidation therapy after cCRT without disease progression in May 2017⁵ and in the European Union in September 2018.⁶ Most recently, it was approved in the US for use in combination with chemotherapy for resectable early-stage disease.⁷

Due to limited evidence in a real-world setting on consolidation durvalumab’s use for patients with unresectable stage III NSCLC,¹ the author sought a greater understanding of its treatment patterns and clinical outcomes in community oncology practices. For their retrospective observational analysis, they used data on newly diagnosed patients from The US Oncology Network’s electronic health record; their treatment window encompassed patients who received their diagnosis and initiated cCRT between November 1, 2017, and October 31, 2019, and who were followed through April 30, 2022. cCRT was defined as “radiotherapy received +/-14 days of receipt of the first dose of chemotherapy.”

The most recent US approval for durvalumab came in August, when it was approved for use in combination with chemotherapy for resectable early-stage disease. | Image Credit: © Vitalii Vodolazskyi-stock.adobe.com

Of the 540 patients included in this study, 61.5% (n = 262) received durvalumab following cCRT and 38.5% (n = 164) only received cCRT. Their median (IQR) age was 70.6 (63.7-76.3) years, less than half (44.6%) were female patients, most reported a White race (72.3%), the median body mass index was 25.4 (22.3-28.7) mg/m², 57.3% were former smokers, 52.8% had diagnosed nonsquamous histology, and 67.8% had an ECOG performance status of 0 to 1.

With the index date being initiation of cCRT after confirmed diagnosis, the investigators saw that patients who received cCRT and durvalumab had the longest median follow-up after the index date and those who only received cCRT, the shortest: 30.4 (13.5-38.0) vs 6.0 (2.6-15.1) months. Carboplatin plus paclitaxel was the most common chemotherapy regimen across both patient groups (86.6%, cCRT and durvalumab; 90.9%, cCRT alone).

However, more patients who received cCRT and durvalumab vs cCRT alone experienced disease progression (41.6% vs 31.3%). Among these patients, most in the former group next received an ICI in combination (37.1%) whereas those in the latter group most often received a chemotherapy combination (46.5%). The most common documented reasons for not receiving consolidation durvalumab were death (28.3%) or disease progression (22.2%), and for discontinuing durvalumab before completing all treatments, adverse events (35.8%) or disease progression (28.4%).

Among patients who received durvalumab after cCRT, the median real-world overall survival (rwOS) was 50.2 (95% CI, 41.4–not reached [NR]) months, and the 12-month survival rate, 83.6% (95% CI, 78.4%-87.6%). The corresponding totals for those who only received cCRT were 11.6 (95% CI, 6.5-15.9) months and 49.1% (95% CI, 40.4%-57.2%). In particular, among those who received consolidation durvalumab, their rwOS was 46.6 (95% CI, 38.3-NR) months and 12-month survival rate, 78.2% (95% CI, 72.5%-82.8%), after consolidation initiation.

Throughout the study observation period, an overall 60.8% had disease progression or died; this was lower in those who received consolidation durvalumab after cCRT vs cCRT alone: 56.5% vs 67.7%. Median real-world progression-free survival (rwPFS) was 28.5 (95% CI, 23.3-36.4) and 6.3 (95% CI, 4.3-9.3) months, respectively, from the index date, and 12-month rwPFS probability, 72.2% (95% CI, 66.3%-77.2%) and 35.0% (95% CI, 27.1%-43.0%). From start of consolidation durvalumab, median rwPFS was 25.4 (95% CI, 20.7-32.7) months, and the 12-month PFS probability, 65.8% (95% CI, 59.7%-71.3%).

Strengths of these findings are that the data on underutilization of durvalumab from death or disease progression and treatment discontinuation echo previous research, which the authors note “suggest the need for more effective induction therapy for patients with unresectable stage III NSCLC, to allow a greater number of these patients to have stable disease and continue consolidation treatment.” They also highlight gaps in treatment strategies for ICIs that serve to strengthen treatment adherence and outcomes.

“While durvalumab addresses a critical need for patients with unresectable stage III NSCLC,” they concluded, “our study underscores the need for additional treatment strategies to address the limitations of consolidation treatment with ICI therapy and explore the best mode of application of ICI in this patient population.”

References

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2. Auperin A, Le Pechoux C, Rolland E, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010;28(13):2181-2190. doi:10.1200/JCO.2009.26.2543

3. Bradley JD, Hu C, Komaki RR, et al. Long-term results of NRG Oncology RTOG 0617: standard- versus high-dose chemoradiotherapy with or without cetuximab for unresectable stage iii non-small-cell lung cancer. J Clin Oncol. 2020;38(7):706-714. doi:10.1200/JCO.19.01162

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6. Imfinzi (duvalumab). European Medicines Agency. Updated October 23, 2024. Accessed November 27, 2024. https://www.ema.europa.eu/en/medicines/human/EPAR/imfinzi

7. Steinzor P. FDA approves durvalumab combination therapy for resectable early-stage NSCLC. AJMC^®. August 16, 2024. Accessed November 27, 2024. https://www.ajmc.com/view/fda-approves-neoadjuvant-adjuvant-durvalumab-for-resectable-nsclc