Maintenance Treatment Patterns: Insights from Advanced Non-Small Cell Lung Cancer

In the treatment of advanced non-small cell lung cancer (NSCLC), maintenance therapy plays a critical role in extending survival and preserving quality of life. But while clinical trials have long set the gold standard for therapeutic protocols, real-world treatment patterns often tell a more complex story—one shaped by patient variability, evolving clinical judgment, and the practical realities of care delivery.

Recent analyses, including those featured in PubMed and presented at oncology congresses such as ASCO, underscore the growing divide between protocol-driven trials and routine clinical practice. While randomized trials like KEYNOTE-189 provide essential structure and efficacy benchmarks, they operate within a controlled ecosystem—excluding patients with comorbidities, unusual performance statuses, or non-standard tumor histologies. Outside these controlled environments, oncologists face the challenge of making nuanced decisions for a far more heterogeneous patient population.

Maintenance Therapy: Principles Meet Practicality

Maintenance therapy, typically initiated after initial disease control with platinum-doublet chemotherapy or chemo-immunotherapy, aims to prolong the benefits of first-line treatment without subjecting patients to undue toxicity. In theory, agents like pemetrexed or pembrolizumab are continued to suppress disease progression, especially in non-squamous NSCLC. But this theory meets variability when translated into the real-world setting.

Studies examining electronic health records and cancer registries reveal that many patients deviate from the strict maintenance regimens outlined in trials. This may reflect toxicity concerns, socioeconomic barriers, or individualized risk-benefit assessments by clinicians. For example, in a retrospective cohort comparing real-world applications of the KEYNOTE-189 regimen, median overall survival ranged between 8 and 11.6 months—markedly lower than the 22-month benchmark achieved in the original trial. These discrepancies highlight how trial outcomes, while aspirational, may not fully capture what is achievable in practice.

Real-World Adaptations and Patient-Centered Care

Maintenance decisions in advanced NSCLC are increasingly shaped by clinical pragmatism. Patients with autoimmune conditions may not tolerate prolonged immunotherapy; others may experience cumulative fatigue, economic hardship, or logistical challenges that preclude strict adherence to therapy schedules. In such cases, oncologists may taper therapy, introduce drug holidays, or opt for alternate regimens—decisions unlikely to be reflected in controlled trial protocols.

Moreover, while trials often exclude older adults or those with multiple comorbidities, these very populations make up a significant portion of real-world NSCLC patients. A patient in their mid-70s with stable cardiovascular disease and borderline renal function might not be eligible for trial participation, yet still requires a tailored maintenance plan that considers quality of life over maximal therapeutic intensity.

Observational studies and registries are now stepping in to fill the evidence gap. Real-world data from the Flatiron Health database and other sources have begun to provide a more granular view of how maintenance therapy is applied across diverse populations. These data sets are not only highlighting deviations but also identifying emerging patterns that may inform more inclusive, flexible guidelines in the future.

Implications for Practice and Protocol Evolution

The growing body of real-world evidence calls for a rethinking of how clinical trial findings are translated into practice. While trials remain essential for establishing safety and efficacy baselines, their findings must be contextualized within the broader spectrum of patient experiences. Personalized care in advanced NSCLC increasingly demands flexibility—both in the interpretation of data and in the application of treatment protocols.

Importantly, this is not a rejection of evidence-based medicine but an evolution of it. Integrating real-world insights allows clinicians to move beyond the binary of trial-eligible versus ineligible and toward a model that prioritizes patient-specific outcomes. It also invites a reevaluation of existing protocols: Could future trials allow for more diverse enrollment? Should endpoints better reflect patient-reported outcomes or real-world progression-free survival?

A Path Forward

The divergence between clinical trial protocols and real-world treatment in advanced NSCLC is not a flaw—it is a reflection of the complexities of modern oncology care. Maintenance therapy, once viewed as a rigid extension of front-line regimens, is now being reframed as a dynamic and patient-centered strategy. Embracing the variability captured in real-world data does more than validate clinical intuition—it advances the field toward a more inclusive, adaptive, and ultimately effective standard of care.

As real-world evidence continues to illuminate the gaps between controlled environments and lived experience, it becomes clear that the future of NSCLC care lies not in rigid adherence to protocol, but in its intelligent adaptation.