Polypharmacy May Shorten Survival in Lung Cancer

Survival outcomes are affected for certain older patients with NSCLC who take five or more oral or inhaled medications.

Older patients with advanced non-small cell lung cancer (NSCLC) receiving immunotherapy treatment tended to have worse survival outcomes if they were taking five or more other oral or inhaled medications, according to a study published in the Journal of Geriatric Oncology.

The researchers analyzed outcomes among patients aged 65 or older whose NSCLC was being treated with a PD-L1 or PD-1 inhibitor with or without chemotherapy. Patients were divided into two groups: the polypharmacy group (those who were taking five or more oral or inhaled medications for other comorbidities, or health issues) and the non-polypharmacy group (those taking none or fewer than five oral or inhaled medications for comorbidities).

“Among community-dwelling older adults, polypharmacy is associated with frailty, hospitalization, poor prognosis and high medical costs,” the researchers wrote. “Most patients with NSCLC have multiple comorbidities and a high frequency of polypharmacy.”

Polypharmacy Impacts on Lung Cancer Survival

Study findings showed that progression-free survival (PFS; the time patients live without their disease worsening) was similar between the polypharmacy and non-polypharmacy groups. The PFS was 6.7 months for the polypharmacy group, compared with 8.5 months for the non-polypharmacy group. However, the difference between these two averages was not statistically significant, meaning that the researchers could not be sure that polypharmacy had an effect on the outcome.

There was, however, a statistically significant difference between the two groups when it came to overall survival (OS), which is defined as the time patients live until death of any cause. The median OS was 17.3 months in the polypharmacy group, compared to 26 months in the non-polypharmacy group.

Additionally, the research showed that during the first year of treatment, the average length of hospital stay was longer and hospitalizations were more frequent for those in the polypharmacy group compared to those who were not taking five or more medications.

This is in line with prior research showing that in elderly patients with colorectal cancer, polypharmacy was associated with worse survival, hospitalization and emergency room visits.

Comorbidities, Other Medications

Patients in the polypharmacy group tended to have more health conditions than those in the non-polypharmacy group. In the entire study population, the most common comorbidities were chronic obstructive pulmonary disease (COPD), tumor without metastasis, diabetes, peptic ulcer disease, prior myocardial infarction (heart attack) and peripheral vascular disease.

The polypharmacy group, specifically, had a significantly higher rate of diabetes and COPD.

Some of these health conditions may require treatments that could weaken the effectiveness of PD-1 or PD-L1 inhibitors — drug combinations commonly referred to as potentially inappropriate prescribing (PIPs).

The most common PIP medications prescribed were benzodiazepines (a type of antidepressant), duplicate drug class prescription, and long-term proton pump inhibitors (PPI, a drug used to reduce stomach acid).

Interestingly, the researchers did not observe a correlation between PIPs and worse survival outcomes. Conversely, those in the polypharmacy group (regardless of PIP) tended to have poorer outcomes overall and experience more side effects.

“We hypothesized that patients with polypharmacy have more comorbidities and are susceptible to chemotherapy-induced toxicities, making it challenging to receive subsequent lines of treatment,” the researchers wrote. “It is unclear whether there is a causal relationship between polypharmacy and short-term survival. However, the vulnerability of patients with polypharmacy may play a role in their short-term survival.”

Ultimately, the researchers mentioned that more research is needed in this field, though the number of medications a patient is taking may lend insight into their potential frailty.

“Overall, this study highlights the importance of understanding the negative effect of polypharmacy on treatment outcomes in older patients with lung cancer, especially those receiving immunotherapy and chemotherapy. The number of medications may also become a useful and simple indicator of vulnerability in older patients with cancer.”

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