Does Disease Burden on PET Predict Outcomes for Advanced NSCLC Patients Treated With First-Line Immunotherapy?


      First-line immunotherapy (IT), with or without chemotherapy (CTX), is now recommended for most patients with advanced non-small cell lung cancer (NSCLC) with no treatable driver mutations. Trials performed before first-line IT became standard suggested that patients with oligometastatic disease (OMD) may have a favorable prognosis and benefit from aggressive local therapy. We reviewed outcomes for NSCLC patients treated with first-line IT at our institution to test the hypothesis that measures of disease burden on staging FDG-PET would have prognostic value and examine if the presence of brain metastases (BM) affects prognosis.


      Advanced NSCLC patients who were staged with FDG-PET and treated with first-line IT between 2015 and 2019 were included in this analysis. Patient, disease, and treatment details were collected. A gradient-based segmentation tool was used to delineate each PET-avid extracranial lesion. Number of extrathoracic lesions, composite metabolic tumor volume (MTV), and presence of BM were tabulated. OMD was defined as having 3 or fewer extrathoracic lesions, with any number of thoracic lesions. Progression-free survival (PFS) and overall survival (OS) rates following initiation of IT were evaluated using the Kaplan-Meier method, and predictors of PFS and OS were assessed using Cox proportional hazards models and log rank tests.


      One hundred twenty-four patients met inclusion criteria, and 1,143 lesions were contoured. Seventy-four patients (60%) had OMD. Median MTV was 88 cc (interquartile range: 33 to 206 cc). Thirty-two patients (26%) had BM. Fifty-eight patients (47%) received IT with CTX. With a median follow-up duration of 17.3 months for surviving patients, the median PFS and OS durations were 8.5 and 36.5 months, respectively. The presence of OMD was associated with favorable PFS (median 13.1 vs. 6.9 months, P = 0.011) and OS (median not reached vs. 20.7 months, P = 0.003). In multivariable models adjusted for performance status, PD-L1 TPS, and receipt of CTX, OMD was associated with favorable PFS (HR = 0.62, P = 0.044) and OS (HR = 0.43, P = 0.018), and high MTV was associated with inferior OS (HR 1.12 per 100 cc, P = 0.048). Among patients who developed progressive disease, the brain was the first site of progression for 12 of 21 patients (57%) with BM at diagnosis and 2 of 55 patients (4%) without BM at diagnosis (P < 0.001). However, the presence of BM at diagnosis was not significantly associated with OS (HR = 0.84, P = 0.642) or PFS (HR = 1.13, P = 0.631) in multivariable models.


      For advanced NSCLC patients treated with first-line IT, having OMD is a favorable prognostic factor. Volume of disease on FDG-PET could provide additional prognostic information. The presence of brain metastases does not seem to affect outcomes, which may reflect the activity of IT in the central nervous system and should be considered when designing clinical trials.
      Author Disclosure: T.Y. Andraos: None. B. Halmos: Consultant; AstraZeneca, Boehringer Ingelheim, Genentech/Roche, Pfizer, Lilly, Foundation Medicine, Guardant Health, Takeda, Novartis, Merck, Bristol-Myers Squibb, Spectrum Pharmaceuticals, TPT Therapeutics. H. Cheng: Research Grant; Roche/Genentech, Spectrum Pharmaceuticals, Vaccinex. Consultant; AstraZeneca, Bayer. C. Huntzinger: None. S. Shirvani: Stock; RefleXion. Stock Options; RefleXion. N. Ohri: Consultant; Merck, AstraZeneca.


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