Impact of Comorbidities on Treatment Patterns and Survival Outcomes in Advanced NSCLC Following ICI Introduction

Key Takeaways:

• The introduction of immune checkpoint inhibitors (ICIs) increased the use of systemic anticancer treatment (SACT) among patients with advanced non–small cell lung cancer (NSCLC), implying their potential to expand care access and treatment options.
• Among patients receiving SACT, those treated with ICIs had significant improvements in overall survival (OS) than those treated with chemotherapy. OS varied across several comorbidities, but most subgroups experienced increases in OS rates, illustrating the improved efficacy of ICIs even among more vulnerable populations.
• Comorbidities make developing treatment plans challenging, and physicians should tailor treatments to meet each individual patient’s medical profile.

Although comorbidities are common in patients with advanced NSCLC, these individuals are often excluded from clinical trials. As a result, the impact of comorbidities on treatment patterns and patient outcomes is unknown.

Considering how comorbidities can influence disease progression and treatment effectiveness, it is important to understand how they might affect outcomes for patients treated with ICIs vs those treated with chemotherapy.

Study Population

Researchers identified 9178 patients with advanced (stage IIIB–IV) NSCLC in Norway who were treated between 2012 and 2021. Out of this group, 4672 received a first-line systemic treatment; this group is known as the SACT cohort.

Out of the 9178 patients with NSCLC, 22% had chronic obstructive pulmonary disease (COPD), 21% had cardiovascular disease (CVD), 10% had type 2 diabetes (T2D), and 6% had rheumatic and musculoskeletal diseases (RMD).

Researchers then observed the influence of comorbidities on treatment patterns and survival outcomes before and after ICI initiation.

Comorbidities and Treatment Patterns

The use of SACT increased among patients after the introduction of ICIs, rising from 52% to 57% in the overall population.

Similar trends were observed in each comorbidity subgroup, although patients with comorbidities were still less likely to receive SACT. SACT increased among patients with COPD from 45% to 51%; CVD, from 38% to 45%; T2D, from 43% to 48%; RMD, from 40% to 50%. This data suggests that ICIs could expand SACT availability for ineligible patients.

Before ICI initiation, 48% of patients received chemotherapy as a first-line treatment. After ICI initiation, 17% of patients received ICI monotherapy, and another 17% received ICI plus chemotherapy.

Patients with CVD had slightly higher rates of ICI monotherapy over combination therapy, 15% and 12%, respectively. The reverse was observed for patients with RMD; 14% received monotherapy and 15% received combination therapy. This data illustrates how the presence and type of comorbidity influence treatment options, as physicians appear less likely to prescribe chemotherapy for patients with CVD than those without.

Comorbidities and Survival Outcomes

Patients in the SACT cohort experienced improved survival outcomes after ICI initiation. In the overall population, 2-year survival increased 2.1-fold after the reception of ICI therapy.

Each comorbidity group experienced higher rates of survival as well. Survival in the T2D group increased threefold, CVD 2.9-fold, COPD 2.8-fold, and RMD 2.4-fold.

ICI monotherapy was associated with higher OS than combination therapy. Patients with CVD had a 2-year OS of 38% when treated with ICI alone and a 2-year OS of 22% when treated with ICI and chemotherapy.

Patients with COPD had a 2-year OS of 33% after ICI monotherapy and 32% after combination therapy. Both rates are significantly higher than the OS for patients treated with chemotherapy, which was 9% before ICI initiation and 17% after.

Patients with T2D had a 2-year OS of 29% after ICI monotherapy and 24% after combination therapy. These rates are substantially higher than the OS of patients treated with chemotherapy alone, which was 4% before ICI initiation and 8% after.

Survival was similar among different treatment patterns for patients with RMD. Chemotherapy had a 2-year OS of 24%, ICI monotherapy had an OS of 23%, and combination therapy had an OS of 20%.

Accounting for Comorbidities in Treatment Decision-Making

The existence of comorbidities complicates decision-making when it comes to developing treatment plans for patients with NSCLC. This study evaluated patients in the same disease groups before and after ICI initiation to understand the effect of comorbidities on treatment patterns and survival outcomes.

ICIs made SACT available to patients who would otherwise be considered ineligible. The significant increases in survival indicate ICIs as an effective treatment option for NSCLC. However, the variations in survival across the different comorbidities illustrate the importance of tailoring treatments toward individual patients.

According to the study’s authors, “[T]he survival gains we observed are primarily attributable to the increased use and effectiveness of ICI therapies, rather than broader improvements in supportive care or diagnostic practices alone.”

References

Hektoen HH, Tsuruda KM, Maehlen MT, Helland Å, Andreassen BK. Real-world outcomes of immunotherapy in advanced NSCLC patients with comorbidities. Br J Cancer. 2026. doi:10.1038/s41416-026-03491-1