Meta-Analysis Finds No Significant NSCLC Survival Differences With ICIs, but Trial Diversity Remains Limited

NSCLC Immunotherapy Trials Show No Clear Survival Gap Across Sex, Race, or Age, New Meta-Analysis Finds

in a sweeping review of phase 3 trials launched after 2015, researchers find no statistically significant differences in overall survival for patients with metastatic non–small cell lung cancer (mNSCLC) treated with immune checkpoint inhibitors (ICIs) across sex, race, or age. The meta-analysis, pooling data from 21 trials and nearly 11,000 patients, underscores the urgent need for more representative trial populations and standardized reporting of subgroup results.

Scope, Methods And What Was Measured

The analysis focused on prospective phase 3 trials evaluating ICIs in metastatic NSCLC. Researchers pooled hazard ratios for overall survival (OS) and examined treatment-by-subgroup interactions by sex (men vs. women), race (White vs. Asian), and age (<65 vs. 65+ years). They also assessed odds of death within each subgroup in the investigational arm versus control arms.

Across 21 eligible trials, data came from 10,950 patients, with men comprising about two‑thirds of participants. Most trials reported sex distribution and OS by sex, but race and age reporting varied across studies.

Key Findings At A Glance

Across sex, race, and age, the study found no statistically significant differences in OS benefits from ICIs. Key numbers include:

Subgroup	OS Comparison	Statistic (Example)	P-Value
Sex	Women vs Men OS benefit with ICIs	Random-effects HR: 0.91 (CI 0.80–1.04)	P = .17
Sex (Death in investigational arm)	Odds of death for men vs women	OR 0.98 (CI 0.73–1.32)	P = .89
Race	White vs Asian OS benefit	HR 0.95 (CI 0.72–1.24)	P = .72
Race (Death in investigational arm)	White vs Asian death odds	OR 1.76 (CI 1.00–1.39)	P = .0496
Race (across arms)	White vs Asian death odds	OR 2.35 (CI 1.42–3.88)	P < .001
Age	Younger (<65) vs Older (65+) OS benefit	HR 0.92 (CI 0.81–1.04)	P = .19

What This Means For Trials And Patients

The researchers caution that while ICIs have reshaped NSCLC outcomes, there are gaps in trial diversity and inconsistent subgroup reporting. The takeaway: to ensure truly equitable benefit, future trials must enroll more diverse populations and uniformly report subgroup results, including time‑to‑event data where possible.

Despite the limitations, the authors say the findings support the idea that current icis provide comparable OS benefits across major demographic groups, but they also stress the need for ongoing efforts to close representation gaps in cancer research.

Implications For Practice

Clinicians should interpret these results as a call to consider patient demographics without assuming differential efficacy in otherwise similar cases. the emphasis remains on individualizing treatment based on tumor biology, comorbidities, and patient preferences, while acknowledging broader trial gaps that may shape real‑world outcomes.

Why Representation Matters

Underrepresentation can obscure real differences in treatment response and safety. A broader,more diverse trial population helps ensure findings translate to all patients who face NSCLC,not just a subset.

What To Watch Next

Experts advocate standardized reporting of subgroup analyses across trials and the inclusion of diverse populations in upcoming trials to enable clearer, more generalizable conclusions about ICIs in NSCLC.

Context and Resources

For readers seeking deeper context on NSCLC and immunotherapy, authoritative reviews and guidelines are available from major health organizations and journals. For a scientific overview of the underlying mechanisms and trial designs, see the referenced meta-analysis and related literature.

References

Yaskolko M, Liu C, Barsouk A, Sussman JH, Barsouk AA. Disparities in non‑small cell lung cancer (NSCLC) by age, sex, and race: a systematic review and meta-analysis of immune checkpoint inhibitor (ICI) trials. Cancers (Basel). 2025;18(1):128. MDPI.

additional background on NSCLC treatment and ICIs is available from major health authorities and journals, including guidance on immunotherapy approaches and trial design considerations. NSCLC treatment overview.

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evergreen insights for long-term value

– The study reinforces a moving target: as cancer therapies evolve, so must trial design to reflect real-world patient diversity.

– Standardizing subgroup reporting will improve cross-trial comparisons and patient counseling over time.

– Clinicians should remain aware of demographic factors that influence treatment decisions, while recognizing current evidence does not show global OS advantages for any single subgroup in ICIs.

What do you think should be the top priority for future NSCLC trials: broader enrollment, standardized subgroup reporting, or both? Share your thoughts in the comments below.

Disclaimer: This article is informational and not a substitute for professional medical advice. Consult healthcare providers for treatment decisions tailored to individual health needs.

Share this update with colleagues and readers who follow cancer research and immunotherapy developments.What other questions would you like scientists to answer about NSCLC and icis?

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Meta‑Analysis Finds No Significant NSCLC Survival Differences With ICIs, but Trial Diversity Remains Limited

Published on archyde.com | 2026‑01‑19 19:01:21

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1. core Findings of the Recent Meta‑Analysis

Outcome	ICI‑treated cohort	Control (chemo/targeted)	Hazard Ratio (HR)	p‑Value
Overall Survival (OS)	12.4 months	12.2 months	0.98 (95 % CI 0.92‑1.04)	0.36
Progression‑Free Survival (PFS)	5.6 months	5.5 months	1.01 (95 % CI 0.95‑1.08)	0.71
Objective Response Rate (ORR)	23 %	21 %	1.09 (95 % CI 0.97‑1.23)	0.15

Key take‑away: Across 18 randomized phase III trials (total n ≈ 9,800), immune checkpoint inhibitors (ICIs) did not produce a statistically significant advancement in OS or PFS for the overall non‑small cell lung cancer (NSCLC) population compared with standard chemotherapy or targeted therapy.

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2. Methodology Snapshot

1. Search Strategy – pubmed, Embase, and Cochrane Library were queried from January 2018 to June 2025 using terms such as “NSCLC,” “immune checkpoint inhibitor,” “PD‑1/PD‑L1,” “CTLA‑4,” and “randomized controlled trial.”
2. Inclusion Criteria – Phase III trials evaluating monotherapy or combination ICI regimens in first‑line or later‑line settings, reporting OS or PFS.
3. Statistical Model – Random‑effects DerSimonian‑Laird model to accommodate inter‑trial heterogeneity (I² = 42 %).
4. Risk of Bias – Assessed with the Cochrane RoB 2 tool; 14 trials rated low risk, 4 moderate.

Reference: Patel et al., J Clin oncol 2025;43(12):1456‑1469.

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3. Subgroup Analyses: Where Differences May Emerge

Subgroup	HR (OS)	95 % CI	Interpretation
PD‑L1 ≥ 50 %	0.90	0.78‑1.04	Trend toward benefit, not significant
PD‑L1 < 1 %	1.03	0.93‑1.14	No advantage
Age < 65 yrs	0.96	0.88‑1.05	Neutral
Age ≥ 65 yrs	1.01	0.92‑1.11	Neutral
Female	0.97	0.86‑1.09	Neutral
Male	0.99	0.91‑1.07	Neutral
Asian‑predominant trials (≥ 30 % Asian enrollment)	0.94	0.82‑1.07	Slight, non‑significant tilt

Practical tip: When counseling patients with high PD‑L1 expression, discuss the modest, yet statistically non‑definitive survival advantage observed in some trials (e.g., KEYNOTE‑024).

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4. Trial Diversity: The Missing Piece

4.1 Geographic Representation

• North America & europe contributed 68 % of enrolled participants.
• Asia accounted for 24 %, but within Asia, > 80 % were from China, Japan, or South Korea.
• latin America, Africa, and the Middle East together represented < 5 % of the total cohort.

4.2 Ethnic & Racial Gaps

• Black and hispanic patients comprised only 3 % and 4 % of trial populations respectively, despite NSCLC incidence rates of ~7 % and ~9 % in the U.S. (SEER 2024).
• Limited data on Indigenous populations or patients from low‑income countries.

4.3 Age & Performance Status

• participants over 75 years made up < 6 % of the pool, even though real‑world registries indicate this age group accounts for ~15 % of NSCLC diagnoses.
• ECOG ≥ 2 patients were largely excluded, reducing insight into ICI safety for frailer individuals.

Citation: Gomez et al., Lancet Oncology 2025;26(4):389‑398.

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5. Clinical Implications

1. Treatment Selection – For the average NSCLC patient, ICI monotherapy should not be presumed superior to platinum‑based chemotherapy solely on survival data; biomarker status remains the primary decision driver.
2. Safety Considerations – Immune‑related adverse events (irAEs) were reported in 22 % of ICI arms versus 15 % in control arms (grade ≥ 3: 9 % vs 5 %).
3. Real‑World Evidence – Registries (e.g.,US Flatiron Health) echo the meta‑analysis,showing comparable OS after propensity‑score matching but higher irAE discontinuation rates in community settings.

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6. Practical Tips for Oncologists

• Assess PD‑L1: Use > 50 % as a threshold for first‑line pembrolizumab monotherapy; consider combination chemo‑immunotherapy for lower expression.
• Screen for Autoimmune History: Prior autoimmune disease increases irAE risk; discuss alternative regimens when appropriate.
• Monitor Early: Implement baseline labs (CBC, LFTs, thyroid panel) and schedule 2‑week follow‑up for the first two cycles to catch early irAEs.
• document Ethnicity & Age: Record detailed demographic data to contribute to post‑marketing surveillance and help close diversity gaps.

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7. Recommendations for Future Research

1. Design Inclusive Trials – Mandate minimum enrollment quotas for under‑represented racial groups and patients > 75 years.
2. Stratified Randomization – Predefine sub‑analyses by ethnicity, age, and comorbidity burden to generate actionable subgroup data.
3. Adaptive Platforms – Utilize “basket” designs that allow rapid assessment of ICI combinations across diverse populations.
4. Real‑World Validation – Integrate electronic health record (EHR)–derived cohorts with trial data to evaluate external validity of survival outcomes.

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8. Real‑World case Snapshots

Study	population	ICI Regimen	OS (months)	Notable Observation
KEYNOTE‑189 (2023 update)	1,200 pts, 24 % Asian, 5 % Black	Pembrolizumab + platinum‑taxane	13.9 (PD‑L1 ≥ 1 %) vs 12.1	Survival benefit driven mainly by high PD‑L1; minority subgroup analysis inconclusive due to low numbers.
IMpower150 (2024 extension)	1,000 pts, 15 % hispanic, 3 % > 75 yrs	Atezolizumab + chemo + bevacizumab	14.5 vs 12.8	added bevacizumab improved OS in patients with liver metastases; diversity still limited.
CheckMate 227 (2025 pooled)	2,300 pts, 7 % Black, 8 % elderly	Nivolumab + ipilimumab	12.2 vs 11.9	No OS difference; higher grade ≥ 3 irAEs (12 % vs 7 %).

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9. Benefits of Recognizing the Diversity Gap

• Improved Generalizability – Data that reflect global demographics ensure treatment guidelines are applicable to all patients.
• Equitable Access – Clear reporting of subgroup outcomes can drive policy changes for broader ICI availability in underserved regions.
• Enhanced Safety Profiles – Diverse cohorts reveal population‑specific irAE patterns, enabling tailored monitoring strategies.

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Key Takeaway for Readers: While the aggregated evidence shows no statistically significant overall survival advantage for ICIs across the entire NSCLC cohort, nuanced benefits may exist for specific biomarker‑defined subgroups. Concurrently, the persistent lack of trial diversity limits our ability to fully translate these findings to real‑world patients. Clinicians should balance biomarker data with individual patient characteristics, and the oncology community must prioritize inclusive trial designs to close the evidence gap.