Lung cancer is the top cause of cancer deaths worldwide, making clinical trials for treating this disease vital. Unfortunately, recruiting trial patients remains a thorny proposition. Discover more about these challenges as well as ways to address them.
Lung cancer is the most common cancer worldwide and the leading cause of global cancer deaths, with an estimated 2.6 million new cases and 1.9 million deaths recorded in 2024. It is also by far the leading cause of cancer death in the US, accounting for about 1 in 5 of all cancer deaths. Each year in the US, more people die of lung cancer than of colon, breast, and prostate cancers combined. About 77% of US lung cancers are non-small cell lung cancer (NSCLC), with small cell lung cancer (SCLC) accounting for 13%. Worldwide, 85% of lung cancers are NSCLC.
Given these grim numbers, the importance of clinical trials for lung cancer treatments cannot be overstated. Unfortunately, recruiting US patients for these trials appears to be becoming more difficult.
One study found that the proportion the proportion of pivotal trials with no US patient enrollment increased from 4.8% in 2014–16 to 19% in 2020–22, while the proportion of trials with at least 10% US patient enrollment declined from 71.4% to 52.3% over those same periods. Multi-regional clinical trials (MRCTs), defined as trials that enrolled at least 5% of patients from each of at least three global regions with no region accounting for 70% or more of patient enrollment, declined from 85.7% in 2014–16 to 66.7% in 2020–22.
The study analysis concluded US patient enrollment in lung cancer pivotal trials may be declining, as well as the proportion of these trials conducted as MRCTs. “Pivotal trials that do not enroll US patients and are not conducted as true MRCTs may have limited applicability to US patients,” the study noted.
A US-based study drawn from a National Cancer Database analysis found only 0.12% of patients with non-small cell lung cancer were enrolled in clinical trials. That is far lower than the 7.1% participation rate for cancer patients overall. Some reasons for this include increasing trial complexity, a short window between diagnosis and treatment, and a lack of clear communication about trial benefits and risks.
Once a patient is diagnosed with lung cancer, they typically start treatment within one to two months. That doesn’t leave much time for these patients to be recruited into a clinical trial, since there are multiple steps involved in qualifying for most lung cancer studies and many patients become ineligible for trials once first-line treatment begins.
Most Phase II and III lung cancer clinical trials require:
The biomarker testing alone can take a median of 27 days, adding to the challenge of recruiting within this limited window.
As is often the case with breast cancer trials, because of this narrow window, lung cancer patients are often approached with trial information while they’re still processing their diagnosis. A systematic review of studies investigating impediments and drivers to lung cancer patient enrollment in clinical trials found that when some new lung cancer patients were provided information about clinical trials, they felt overwhelmed and unable to give proper consideration about whether to participate in the trials.
Biomarker testing is essential because lung cancer trials are now built around specific tumor targets. In a retrospective study, 82% of metastatic NSCLC lung cancer patients were found to have received at least one biomarker test. Biomarker testing and use of biomarker-informed therapies increased for all studied biomarkers, with EGFR rates coming in at 75% and 71%, respectively and ALK at 72% and 89%, respectively.
Even when a trial is focused on a relatively common biomarker like EGFR or ALK, the pool of candidates from which to recruit for studies remains small, in part due to the additional criteria they must meet to qualify for a specific trial. That pool shrinks further for rare biomarkers like rearranged during transfection (RET), which is found in only 1% to 2% of patients with NSCLC.
According to the systematic review mentioned earlier, travel to and from the study site was a major barrier to patients taking part in lung cancer trials. Patients, carers, and clinicians often declined to take part due to the investment of time and money required for travel, as well as the danger travel could present to a lung cancer patient with vulnerable health status.
Another obstacle cited in the review was that many studies required patients manage daily activities at a certain level. A reduced ability to do so often disqualified the patient from the trial. Plus, many trials tend to be focused on advanced stage IV lung cancer, leaving out patients who haven’t progressed that far in their disease.
Some underserved populations are disproportionately affected by lung cancer. For instance, Black Americans with lung cancer are less likely to be diagnosed at an early stage of the disease and less likely to receive surgical treatment for it. In fact, they are less likely to receive any treatment at all compared to white Americans. This means Black Americans suffer poorer outcomes from lung cancer.
This lack of balance extends to clinical trials. One study noted while rates of nonwhite and female participation in US lung cancer trials have increased markedly over the past couple of decades, they still are not at parity with the incidence of lung cancer in these populations. Fear and mistrust appear to be significant barriers to their participation, as well as lack of information as to the existence of suitable clinical trials.
The review noted lung cancer patients and carers expressed their desire for information that is comprehensive and in plain language to clarify what participation in the trial would entail. Such information would include frequency of treatment, potential side effects, and a broader history of clinical trials to help patients understand the research process as a whole and feel best prepared to take part.
According to the review, the way in which clinical trial information was presented and who presented it also influenced patient decision-making. Many former trial participants reacted positively to particular words or phrases suggesting a strong or more aggressive approach to cancer treatment. They also appreciated clinicians using “we” and “our” when speaking about treating the cancer, which suggested a shared treatment effort that helped patients feel less isolated. For some patients, trust in their provider alone was reason enough for them to participate in a trial.
