Patients with metastatic/recurrent NSCLC receiving pembrolizumab are more likely to receive it as a single agent and less likely to receive combination chemoimmunotherapy (CIT) if they have a higher comorbidity score, Australian research shows.
The finding, from a retrospective Victorian study, confirms anecdotal evidence of chemotherapy avoidance in patients with comorbidities such as COPD, stroke, diabetes and heart disease.
The cohort comprised 61 patients with newly diagnosed metastatic or unresectable NSCLC, without driver mutations and with a high expression of PD-L1 as defined by tumour proportional score (TPS) ≥ 50%.
The majority (77%) were treated with pembrolizumab monotherapy and the other 23% with pembrolizumab-based CIT.
Charlson Comorbidity Index (CCI) score was the only patient factor significantly associated with the type of treatment received.
“As a continuous variable, the mean CCI was higher (3.38) in those receiving single agent immunotherapy compared to those receiving CIT (2.36), which was significant (P = 0.042),” the study said.
“A patient with a higher comorbidity score of 2 or greater was less likely to receive chemotherapy in addition to immunotherapy (OR = 0.15, P = 0.003, 95% CI = 0.04–0.57).”
The investigators, from St Vincent’s Hospital Melbourne, Monash Health and Chris O’Brien Lifehouse, said the influence of CCI on treatment selection has not yet been assessed in the immunotherapy era.
They found both age and ECOG status were insufficient as independent variables to correlate with treatment selection in their cohort.
“Given its prognostic significance and likely influence on therapeutic selection, it would be beneficial for future studies to consider including the comorbidity index in addition to traditional measures like ECOG,” they wrote.
The study also found that larger primary tumour size was associated with the use of CIT (P = 0.014).
“Primary tumours over 5 cm in size were 3.74 times more likely to have received combination CIT (OR = 3.74, P = 0.043, 95% CI = 1.04–13.42).”
“Given the importance of perceived disease burden in influencing treatment decisions, a system for stratifying patients based on tumour burden could be explored,” the study authors said.
Subdiaphragmatic metastases, which included disease of the abdominal lymph nodes and/or the adrenal glands, were also associated with the use of CIT (P=0.027).
“The association of subdiaphragmatic lesions with CIT could reflect the impression of extensive disease and requires further investigation.”
Other frequent and critical sites of metastatic disease including thoracic lymph nodes, pleural effusion, bone, brain and liver were not associated with receipt of either single agent or combination therapy.
The investigators noted limitations of the study including small cohort size, potential selection bias given the staggered approval of pembrolizumab onto the PBS, and possible influence of the COVID-19 pandemic during which time clinicians may have opted to avoid using chemotherapy.
However they said their evaluation of patient and disease characteristics influencing treatment selection in PD-L1-high metastatic NSCLC was important.
“There is a lack of compelling data for superiority in oncological outcomes between first-line CIT versus pembrolizumab alone, emphasising the importance of factors influencing therapeutic choice.”
“Further prospective studies could use comorbidity status and a validated disease burden score to stratify patients alongside conventional measures such as ECOG,” they concluded.
The study was published in the Internal Medicine Journal [link here].