Sujay Shankar

Background: Lung cancer is the second most common type of cancer and the deadliest cancer type in the U.S and worldwide. Non-small cell lung cancer (NSCLC) constitutes about 80-85% of all lung cancers and only has a 7% five-year survival rate if metastatic.^1,2 Immunotherapy, specifically anti-PD-1 antibody drugs, is emerging as a promising treatment for patients with PD-L1 expressing NSCLC. PD-L1 is a ligand expressed on tumor cells and PD-1 is expressed on T cells. When PD-1 binds to PD-L1, tumor cells successfully evade recognition and destruction by T cells. In PD-L1 expressing NSCLC, anti-PD-1 antibody drugs bind to PD-1 on T cells, preventing tumor cell evasion and enhancing the T-cell immune response.³

Objective: Investigate Anti-PD-1 mechanism of action and compare the clinical efficacy of chemotherapy and anti-PD-1 immunotherapies for patients with NSCLC.

Search Methods: The clinical efficacy of anti-PD-1 antibody immunotherapy is compared to chemotherapy, CTLA-4 targeting drugs, different anti-PD-1 antibody drugs, and anti-PD-L1 antibody drugs in patients with PD-L1 expressing NSCLC. Patient outcomes following combination treatment and anti-PD-1 antibody immunotherapy in patients with PD-L1 negative NSCLC are also included in this research. The endpoints for clinical efficacy cover overall survival rate (OSR), objective response rate (ORR), adverse effects (AE), and progression free survival (PFS). Each study has a sample size of at least 100 patients.

Results: NSCLC patients taking pembrolizumab (anti-PD-1 antibody drug) had an OSR that was approximately three times higher than those taking docetaxel (chemotherapy) over a 36 month period.⁴ Patients taking both pembrolizumab and ipilimumab (CTLA-4 targeting drug) had a slightly decreased SOR and increased AE compared to patients taking pembrolizumab only.⁵ There was no significant difference in ORR and OSR among patients taking different brands of anti-PD-1 antibody drugs.⁶ Patients taking atezolizumab (anti-PD-L1 antibody drug) had similar ORR, PFS, and number of AE to patients taking pembrolizumab, but had a lower OSR by about 2 months.⁷ No immunotherapy drugs were significantly more effective than chemotherapy in patients with PD-L1 negative NSCLC. A recent clinical trial revealed that 24% of NSCLC patients taking combination treatment of anti-PD-1 antibody immunotherapy and chemotherapy had a complete response compared to 2.2% of patients taking chemotherapy alone.⁸

Conclusions: Anti-PD-1 and Anti-PD-L1 antibody drugs are currently some of the most effective immunotherapies for patients with PD-L1 expressing NSCLC. Future treatments for NSCLC are focused on combination treatment, DNA repair targeting drugs, and cell therapy.

Works Cited:

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660
2. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7-33. doi:10.3322/caac.21654
3. Thai AA, Solomon BJ, Sequist LV, Gainor JF, Heist RS. Lung cancer. Lancet. 2021;398(10299):535-554. doi:10.1016/S0140-6736(21)00312-3
4. Herbst RS, Garon EB, Kim DW, et al. Long-Term Outcomes and Retreatment Among Patients With Previously Treated, Programmed Death-Ligand 1‒Positive, Advanced Non‒Small-Cell Lung Cancer in the KEYNOTE-010 Study. J Clin Oncol 2020; 38:1580.
5. Boyer M, Şendur MAN, Rodríguez-Abreu D, et al. Pembrolizumab Plus Ipilimumab or Placebo for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50%: Randomized, Double-Blind Phase III KEYNOTE-598 Study. J Clin Oncol 2021; 39:2327.
6. Wu K, Fu Y, Zeng D, Chen T, Wang C, Jiang J. A retrospective cohort study of sintilimab and pembrolizumab as first-line treatments for advanced non-small cell lung cancer. J Thorac Dis. 2022;14(3):679-688. doi:10.21037/jtd-22-225
7. Zhang Y, Zhou H, Zhang L. Which is the optimal immunotherapy for advanced squamous non-small-cell lung cancer in combination with chemotherapy: anti-PD-1 or anti-PD-L1? J Immunother Cancer. 2018;6(1):135. doi:10.1186/s40425-018-0427-6
8. Forde PM, Spicer J, Lu S, et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med. 2022;386(21):1973-1985. doi:10.1056/NEJMoa2202170