Beyond Concurrent Chemoradiation: The Emerging Role of PD-1/PD-L1 Inhibitors in Stage III Lung Cancer

Abstract

Concurrent chemoradiation (cCRT) with platinum-based chemotherapy is standard-of-care therapy for patients with stage III unresectable non-small cell lung cancer (NSCLC). Although cCRT is potentially curative, 5-year overall survival has hovered around 20%, despite extensive efforts to improve outcomes with increasing doses of conformal radiation and intensification of systemic therapy with either induction or consolidation chemotherapy. PD-1/PD-L1 immune checkpoint inhibitors have demonstrated unprecedented efficacy in patients with stage IV NSCLC. In addition, preclinical and early clinical evidence suggests that chemotherapy and radiation may work synergistically with anti-PD-1/PD-L1 therapy to promote antitumor immunity, which has led to the initiation of clinical trials testing these drugs in patients with stage III NSCLC. A preliminary report of a randomized phase III trial, the PACIFIC trial, demonstrated an impressive increase in median progression-free survival with consolidative durvalumab, a PD-L1 inhibitor, compared with observation after cCRT. Here, we discuss the clinical and translational implications of integrating PD-1/PD-L1 inhibitors in the management of patients with unresectable stage III NSCLC. .

Safety and Feasibility of Lung Resection After Immunotherapy for Metastatic or Unresectable Tumors

“…), as well as multiple courses of immunotherapy (the mean number of doses in this series was 21), before resection is considered. In addition, recent studies demonstrating impressive outcomes in patients with stage III NSCLC undergoing chemoradiation followed by immunotherapy will likely result in further application of these agents to patients with operable disease (9, 10). …”

Senescent cells re‐engineered to express soluble programmed death receptor‐1 for inhibiting programmed death receptor‐1/programmed death ligand‐1 as a vaccination approach against breast cancer

“…PD‐L1 inhibitor has been approved for use as monotherapy . Generally, preclinical trials have managed to combine cancer vaccines with commercially available antibodies against PD‐1/PD‐L1 or other inhibitory receptors .…”

“…Therefore, further studies PD-L1 inhibitor has been approved for use as monotherapy. 31 Generally, preclinical trials have managed to combine cancer vaccines with commercially available antibodies against PD-1/PD-L1 or other inhibitory receptors. 32 However, a recent study showed that not only commercial antibodies interrupted PD-1/PD-L1 interaction, but a similar effect was also obtained by the soluble form of PD-1, detected in blood from patients with autoimmune diseases.…”

Immunotherapy for Uterine Cervical Cancer Using Checkpoint Inhibitors: Future Directions

“…However, PD-L1 is upregulated following irradiation and chemotherapy, prompting T-cell apoptosis and anergy upon ligation to PD-1 and restricting the immune response. The addition of anti-PD-1/PD-L1 blocks this interaction, facilitating synergistic antitumor immunity [34]. In prospective clinical studies, the combination of CCRT and an ICI was investigated, demonstrating positive effects [34].…”

“…The addition of anti-PD-1/PD-L1 blocks this interaction, facilitating synergistic antitumor immunity [34]. In prospective clinical studies, the combination of CCRT and an ICI was investigated, demonstrating positive effects [34]. In a phase III trial of lung cancer that treated patients with durvalumab after CCRT, the median PFS was 17.2 months, which is significantly longer than the 5.6 months seen for placebo [35].…”