Does Very Poor Performance Status Systematically Preclude Single Agent Anti-PD-1 Immunotherapy? A Multicenter Study of 35 Consecutive Patients

SIMPLE SUMMARY: Immunotherapies prolong survival of metastatic non-small-cell lung cancer patients. However, their efficacy in patients with very poor general condition is unknown. Best supportive care is the standard of care for these patients because chemotherapy is more toxic and less effective than for patients with good general condition. Most patients die within 1 to 4 months of diagnosis. Consecutive metastatic non-small-cell lung cancer patients with very poor general condition receiving compassionate immunotherapy were accrued by 12 French thoracic oncology departments, over 24 months. Tolerance was acceptable. Overall, 20% of patients were alive at 1 year, and 14% at 2 years. We feel that our study results might suggest that some patients with a very poor general condition (namely those without brain metastases or heavy smokers) could derive long-term benefit from immunotherapy as salvage therapy. We initiated such a prospective phase 2 trial based on these results, which is a cause for hope. ABSTRACT: Anti-PD-1 antibodies prolong survival of performance status (PS) 0–1 advanced non-small-cell lung cancer (aNSCLC) patients. Their efficacy in PS 3–4 patients is unknown. Conse- cutive PS 3–4 aNSCLC patients receiving compassionate nivolumab were accrued by 12 French thoracic oncology departments, over 24 months. Overall survival (OS) was calculated using the Kaplan-Meier method. Prognostic variables were assessed using Cox proportional hazards models. Overall, 35 PS 3–4 aNSCLC patients (median age 65 years) received a median of 4 nivolumab infusions (interquartile range [IQR], 1–7) as first- (n = 6) or second-line (n = 29) therapy. At a median of 52-month follow-up (95%CI, 41–63), 32 (91%) patients had died. Median progression-free survival was 2.1 months (95%CI, 1.1–3.2). Median OS was 4.4 months (95%CI, 0.5–8.2). Overall, 20% of patients were alive at 1 year, and 14% at 2 years. Treatment-related adverse events occurred in 8/35 patients (23%), mostly of low-grade. After adjustment, brain metastases (HR = 5.2; 95%CI, 9–14.3, p = 0.001) and <20 pack-years (HR = 4.8; 95%CI, 1.7–13.8, p = 0.003) predicted worse survival. PS improvement from 3–4 to 0–1 (n = 9) led to a median 43-month (95%CI, 0–102) OS. Certain patients with very poor general condition could derive long-term benefit from nivolumab salvage therapy.