Pembrolizumab for advanced non-small cell lung cancer (NSCLC): Impact of autoimmune comorbidity and outcomes following treatment completion

Abstract

Introduction Pembrolizumab, an immune-checkpoint inhibitor, is approved for first-line treatment of metastatic NSCLC in patients with tumours expressing programmed death-ligand 1 (PD-L1) with tumour proportion score (TPS) of ≥50%. We aimed to clarify some uncertainties regarding use of immunotherapy in patients with previous autoimmune (AI) disorders and assess real-world outcomes following treatment completion. Methods We performed a retrospective case record review of 82 patients with tumours expressing PD-L1 at TPS ≥ 50% and receiving first-line Pembrolizumab. Survival was estimated using the Kaplan Meier method. Results After 36.93 months (IQR: 34.37–40.20) median follow-up, median OS was 13.6 months (95% CI 8.9–19.3). There were 10 patients (12%) with AI co-morbidities and there was a trend toward improved median OS for this group versus those without AI comorbidity, 42 months (14.87-NR) versus 10.7 months (7.3–17.8), p = 0.073. Sixteen patients (20%) with nonprogressive disease at 2 years had significantly better median OS compared to those who did not complete 2 years of treatment, NR (42- NR) and 8.7 (5.8–14.1), p < 0.001. Immune related adverse events (irAE) of any grade occurred in 90% of the AI cohort compared with 70.8% of patients without AI comorbidity. Low grade adrenal insufficiency was the only irAE which occurred at a significantly higher rate in the AI group, p = 0.02. Conclusion Patients with previous AI diseases tolerate treatment well, and there is a non-significant trend for improved outcomes in this group. Patients who complete the course of pembrolizumab have significantly better survival outcomes than those who do not.

Safety and efficacy of immune checkpoint inhibitors in advanced cancer patients with autoimmune disease: A meta-analysis

“…Among these, three studies were from Japan, 20 , 21 , 24 one from Korea, 28 two from Italy, 22 , 32 one from France, 25 two from Germany, 26 , 33 one from the UK, 29 one from Switzerland, 23 one from Holland, 27 and two from the US. 34 , 35 Nine studies reported on non-small cell lung cancer (NSCLC), 20–22 – 24 , 25-28 – 29-33 – 35 seven on melanoma, 22–25 – 27–32 – 34 , 35 and three on metastatic renal cell cancer and urothelial carcinomas. 22 , 23 , 35 Among AIDs, ILD and endocrine AID were most frequently mentioned.…”

“…R software (version 4.1.3) was used for data analyses. RR was used to re ect the incidence of irAEs of any grade and grade ≥ 3 [15][16][17][18][19][20][21] . If the studies recorded HR for PFS or OS, we adopted the results.…”

“…Clinically, immunosuppressants such as steroids are commonly used to control irAEs. Since only two studies have discussed the use of immunosuppressants to control irAEs, we cannot rely on the limited data to accurately analyze results [15,19] . Zhang et al found that the OS and PFS were signi cantly shortened in the administration of corticosteroids [32] .…”

“… 20–27 If the studies recorded HR for PFS or OS, we adopted the results. For some studies 20–22 – 24–26 – 28 , 29 that lacked HR for PFS or OS values, we downloaded the Kaplan – Meier curves, used the specialized software (Engauge Digitizer) to extract the curves’ data, and estimated HR using Jayne F Tierney’s spreadsheet. 30 Calculations were independently repeated twice to obtain precise results.…”

“…These studies mainly took place in Asia and Europe, with only one in the US. Among these, three studies were from Japan [15,16,22] , one from Korea [17] , two from the Italy [18,25] , one from Germany [26] , one from the UK [19] , one from Switzerland [20] , one from Holland [27] , and one from the US [21] . Seven studies focused on non-small cell lung cancer [15-17, 19, 22, 26] , four reported melanoma [18,21,25,27] , and two involved in metastatic renal cell cancer and urothelial carcinoma [18,20] .…”