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Systemic therapy underutilized in NSCLC treatment, particularly among older patients
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Most patients with metastatic non–small cell lung cancer in the general population did not receive systemic therapy, especially if they were older or had squamous histology, according to the results of a retrospective analysis.
Patients who did receive first- and second-line systemic treatment demonstrated outcomes comparable to those achieved on clinical trials, the researchers also found.
“Although there are data supporting the benefit of systemic treatment in the majority of patients with metastatic NSCLC, including elderly patients and lesser performance status patients, there appears to be a reticence to employ systemic therapy,” Natasha B. Leighl, MD, MMSc, of the Princess Margaret Health Centre in Toronto, Canada, and colleagues wrote. “This is likely multifactorial … For example, chemotherapy toxicity without a larger survival benefit may lead some patients, referring physicians and even oncologists not to consider systemic therapy for advanced NSCLC. Access issues, including diagnostic and treatment wait times, the geographic proximity of treatment and treatment funding may also contribute.”
Oncologists may also be reluctant to employ systemic therapy based on a perception that outcomes in the real world are unlikely to match those achieved in the clinical trial population, Leighl and colleagues wrote.
Researchers used the Ontario Cancer Registry to identify 8,113 Canadian patients (median age, 68 years; 54% male) diagnosed with stage IV NSCLC between 2005 and 2009. Ninety-two percent of patients received treatment at regional cancer centers and 70% of patients met with a medical oncologist at least once.
Thirty-nine percent of patients had adenocarcinoma histology and 14% had squamous carcinoma. Four percent of patients had rare subtypes — including mixed adenosquamous, sarcomatoid, carcinoid and poorly differentiated large cell types — and 43% of patients had NSCLC not otherwise specified.
Median follow-up was 16.9 months (range, 0.03-72.6).
A majority (76%) of patients did not receive chemotherapy. The other 24% of patients received at least one line of chemotherapy: 16% underwent first-line chemotherapy only and 8% of underwent first- and second-line chemotherapy.
The proportion of patients who underwent chemotherapy increased from 19% in 2005 to 26% in 2009 (P < .0001).
The median age of patients who received chemotherapy was 63 years (range, 30-89). Patients aged 70 years or older were significantly less likely to undergo chemotherapy (OR = 0.3; 95% CI, 0.26-0.33). Patients with adenocarcinoma were more likely to receive chemotherapy than patients with squamous histology (OR = 1.3; 95% CI, 1.1-1.53).
Almost all patients (89%) who received first-line chemotherapy were treated with platinum doublets, and the most frequently used doublets were cisplatin/gemcitabine (22%) and carboplatin/gemcitabine (22%). The most common second-line treatments were docetaxel (52%) and pemetrexed (Altima, Lilly; 41%).
Patients who received both first- and second-line chemotherapy achieved a median OS of 16.2 months (95% CI, 15.1-17) and patients who only received first-line chemotherapy achieved a median OS of 8.2 months (95% CI, 7.7-8.6). However, patients who did not receive chemotherapy demonstrated a median OS of 3.3 months (95% CI, 3.2-3.4).
Patients who received cisplatin/gemcitabine as first-line chemotherapy demonstrated a longer median OS (11.6 months; 95% CI, 10.3-13.8) than those treated with other regimens (range, 8.4-9.3 months). The survival benefit associated with cisplatin/gemcitabine persisted in analyses adjusted for sex, year of diagnosis and pathological subtype (HR = 0.75; 95% CI, 0.65-0.87).
Female sex (P < .0001) and adenocarcinoma (P = .01) also were linked to a lower risk for death.
Treatment with pemetrexed conferred a longer median OS than docetaxel among patients who received first- and second-line chemotherapy (19.8 months vs. 14.1 months).
The researchers acknowledged their inability to access certain patient information — including data pertaining to comorbidities, performance status and the use of certain anticancer drugs — as a limitation of their study.
“Further investigation is needed to better examine the characteristics of the untreated majority of patients with advanced NSCLC to identify other currently unknown factors contributing to low treatment rates,” Leighl and colleagues concluded. “This will allow the rigorous exploration of the key determinants of the low rates of systemic therapy utilization identified in this study and others and thus allow the development of better evidence-based strategies to improve treatment access and outcomes in this population.”
Referral bias may be one reason for which patients with advanced NSCLC are undertreated, Sai-Hong Ignatius Ou, MD, PhD, of the Chao Family Comprehensive Cancer Center in Orange, California, wrote in an accompanying article.
“Noonan [and colleagues] reported that in 2009, only 54% of patients with advanced NSCLC were referred to medical oncologists,” Ou wrote. “In [this] study, 70% of the patients were referred to medical oncologists. Continuous education of primary care physicians by dedicated thoracic oncologists (ie, the treatment of lung cancer has advanced over time and chemotherapy options have increases and are more tolerable and efficacious) may help increase the referral rate.”
There are also new chemotherapy, targeted and immunotherapy agents available since the timespan of this study, Ou wrote.
“It will be important to continue to capture the real-world usage of these novel and expensive drugs to help us to appreciate whether positive clinical trial results are being implemented on a daily basis … and to identify ways to overcome barriers to their optimal use,” Ou wrote. – by Cameron Kelsall
Disclosure: The researchers report no relevant financial disclosures.
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