Precision oncology has reshaped how advanced non-small cell lung cancer (NSCLC) is diagnosed, studied and treated. As more molecularly defined subtypes are identified, treatment decisions increasingly depend on understanding the genomic drivers of each patient’s cancer, rather than relying only on tumor histology or broad clinical characteristics.
This shift has been especially important in advanced NSCLC, where actionable alterations can guide the use of targeted therapies. But the growing number of biomarker-directed treatment options has also placed greater emphasis on testing infrastructure, turnaround times and equitable access to comprehensive molecular profiling.
Global Head of Oncology
Boehringer Ingelheim
For rarer subtypes such as HER2/ERBB2-mutant NSCLC, these issues are particularly important. HER2-mutant NSCLC represents a small subset of NSCLC, but one with substantial unmet need and a history of slower progress compared with more established biomarker-defined groups.
To discuss the clinical research and treatment implications of precision oncology in advanced NSCLC, Xtalks spoke with Itziar Canamasas, PhD, Global Head of Oncology at Boehringer Ingelheim.
Molecular Testing Is Now Central to the Treatment Journey
The rise of precision oncology has made biomarker testing a core part of advanced NSCLC care. Molecular profiling can help identify genomic alterations that may influence prognosis, treatment selection and clinical trial eligibility.
For Canamasas, the issue is no longer whether molecular testing matters, but whether patients can access the right testing early enough to inform treatment decisions.
“It is important to identify specific genomic alterations early because it helps determine which treatments are most likely to work for the patient’s unique lung cancer,” said Canamasas.
“The biggest gap today is not science, but access to timely and comprehensive testing.”
— Itziar Canamasas
Next-generation sequencing (NGS) is expected to become increasingly important as more targeted therapies enter development. Comprehensive testing can help detect actionable mutations and other tumor aberrations across a broader panel of genes, supporting more individualized treatment strategies.
But testing only changes care when results are available in time to guide initial decision-making. In advanced NSCLC, delays in molecular results can affect whether patients receive biomarker-matched therapy early in the treatment journey.
Canamasas said the industry must focus not only on expanding testing, but also on improving how quickly results reach care teams.
“I hope that as a healthcare industry, we will be able to accelerate these test results, delivering them to care teams faster so that they can start patients on targeted treatments that much sooner,” she said.
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HER2-Mutant NSCLC: A Smaller Subtype with Substantial Clinical Need
HER2/ERBB2-mutant NSCLC is a rare, molecularly defined form of lung cancer. Because it accounts for only a small proportion of NSCLC cases, it has historically received less research and drug development attention than some other biomarker-driven subtypes.
That small patient population creates scientific and operational challenges. It can limit the pace of evidence generation, complicate recruitment and make it harder to conduct large randomized trials using traditional designs.
“HER2-mutant non-small cell lung cancer is a smaller, molecularly defined subset of lung cancer,” said Canamasas. “It occurs only in around 2% to 4% of cases, and because of its size, it has historically lagged behind other biomarker-driven lung cancers in research but also in drug development.”
The unmet need is also shaped by the biology and clinical behavior of the disease. Canamasas noted that HER2-mutant NSCLC has been associated with aggressiveness and poor prognosis, underscoring the need for more effective options tailored to this subgroup.
More broadly, advanced NSCLC remains difficult to treat, particularly when the disease is diagnosed after it has spread locally or to distant organs. At that point, curative treatment is often not feasible and long-term outcomes remain challenging.
Rethinking Trial Design for Smaller Genomic Subtypes
As lung cancer becomes more molecularly segmented, clinical development must adapt. Traditional trial models can be inefficient when patient populations are small, geographically dispersed and dependent on molecular testing for identification.
Canamasas pointed to basket, umbrella and adaptive trial designs as important tools for studying rare genomic subtypes more efficiently. These approaches can allow researchers to evaluate multiple treatments, biomarkers or disease cohorts within a single trial infrastructure.
“When designing trials in these smaller, molecularly defined populations, one of the most important considerations is how to improve efficiency while still capturing robust data,” she said.
Adaptive designs can also allow data to be analyzed during the study and used to refine aspects of the trial as evidence emerges. In oncology, where treatment standards can evolve quickly, this flexibility may help development programs remain clinically relevant while still generating rigorous evidence.
“This ability to use these platform trials will help us evaluate multiple treatments or approaches within a single study, and the design can be adapted based on the data, making trials much more efficient and impactful,” Canamasas explained.
For clinical researchers, this reflects a broader challenge in precision oncology: how to maintain evidence quality while designing studies that are feasible for rare biomarker-defined groups. The answer may involve more flexible protocols, stronger diagnostic networks, earlier molecular screening and closer alignment between sponsors, investigators, regulators and clinical sites.
Looking into Patient-Centered Outcomes
In targeted oncology, treatment benefit has often been measured through endpoints such as objective response rate, progression-free survival and overall survival. These measures remain critical, particularly in advanced disease. But as therapies become more personalized, Canamasas said the field should also consider how treatment affects patients’ daily lives.
“As targeted therapies become more personalized, we need to rethink what success looks like,” she said. “More time alone is not enough. It’s about the quality of that time.”
This is an important consideration for oncology drug development, where clinical benefit may include not only tumor control but also tolerability, time away from the hospital and the ability to maintain everyday function.
“The most meaningful progress is progress that puts the person, not just the biology, at the center of care.”
— Itziar Canamasas
Targeted therapies are designed to act more selectively on cancer-associated drivers than traditional chemotherapy. Although safety profiles vary by therapy and patient population, this approach has contributed to a broader discussion about how to evaluate benefit beyond traditional efficacy measures.
“Our goal is that patients can live their lives spending less time in the hospital and often tolerate these treatments much better than traditional chemotherapy,” said Canamasas.
For trial design, this may increase the importance of patient-reported outcomes, symptom burden, functional measures and real-world evidence that captures how treatments perform outside controlled study settings.
What Comes Next in Advanced NSCLC Research
Looking ahead, improving outcomes in advanced NSCLC will likely require earlier detection, broader molecular testing, more precise combination strategies and a deeper understanding of resistance.
Canamasas noted that early detection remains difficult in NSCLC because symptoms may be absent or nonspecific, and diagnostic delays can occur. Many patients are diagnosed after the disease has spread locally or to distant organs.
“Comprehensive tumor profiling could help to identify more actionable mutations and aberrations, tailor treatments and then also help us understand how and why resistance may occur to current treatments,” said Canamasas. This is increasingly important as patients move through multiple lines of therapy and tumors evolve under treatment pressure.
Understanding resistance could support more rational treatment sequencing, including switching therapies when a new resistance mechanism emerges or adding another therapy to block more than one relevant pathway.
Canamasas also pointed to the potential for combination strategies involving chemotherapy, immunotherapy, immune activation approaches and targeted therapies. In NSCLC, the challenge will be identifying which combinations are biologically justified, clinically tolerable and appropriate for specific molecular subgroups.
Access and Equity Remain Central to Precision Oncology
Precision oncology depends on more than the availability of targeted therapies. It also depends on whether patients can receive timely diagnosis, comprehensive testing and access to appropriate treatment regardless of geography, care setting or socioeconomic status.
Disparities in molecular testing and access to specialty oncology care can limit the impact of scientific advances. For rare subtypes such as HER2-mutant NSCLC, gaps in testing may mean that some patients are never identified as candidates for biomarker-directed treatment or relevant clinical trials.
Canamasas said addressing disparities in access to care will be important for ensuring patients can benefit from advances in molecular oncology. She also emphasized the need for continued research into lifestyle, environmental and genetic factors that contribute to NSCLC risk and outcomes.
For the clinical research ecosystem, the message is clear: advances in targeted therapy must be matched by advances in testing access, trial design and evidence generation.
As NSCLC becomes increasingly segmented by molecular subtype, the success of precision oncology will depend on how quickly and equitably the healthcare system can connect genomic information to treatment decisions.
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