The researches find that the Platinum-based Chemotherapy Still Have a Role in First-line Treatment of Advanced Non–Small-Cell Lung Cancer. Therefore A man in his mid-60s with a 12 pack-year smoking history presented to his primary care physician for unrelenting chest pain. Because A chest computed tomography scan revealed a 9.4 × 7.8 cm right upper lobe mass extending to the posterior pleural surface; with an associated trace pleural effusion.
Four weeks later, the patient presented to the emergency department with dyspnea, palpitations; and hypoxia. But computed tomography angiogram revealed interval growth of the right upper lobe mass; now 11.4 × 9.0 cm, with an associated large right pleural effusion displacing the mediastinum into the left thorax and compressing the right heart (Figure 1A).
He is admit to the intensive care unit. A chest tube was placed; and the dominant lung mass was biopsied, therefore revealing poorly differentiated adenocarcinoma. Because His programmed death-ligand 1 (PD-L1) expression level was 90% using the 22C3 antibody (Dako, Santa Clara, CA; Figure 2). A 10-gene genomic panel did not identify actionable tumor mutations.
The emergency department
A staging positron emission tomography scan revealed hyper metabolic uptake at the site of the primary lung mass, intrathoracic nodal metastases; and widespread metastases to bone; liver, and adrenal glands. A brain magnetic resonance imaging scan was negative for intracranial metastases. The development of programmed cell death-1 (PD-1) inhibitors; such as nivolumab and pembrolizumab; and the PD-L1 inhibitor atezolizumab, has revolutionized the treatment of metastatic non–small-cell lung cancer (NSCLC).
Nivolumab and atezolizumab are approved for previously treated patients regardless of PD-L1 expression level; whereas pembrolizumab is approved as monotherapy for patients who are treatment nïve with PD-L1 levels greater than or equal to 50%, previously treated with PD-L1 levels greater than or equal to 1%, and regardless of PD-L1 expression in combination with platinum and pemetrexed in non squamous NSCLC.
Monotherapy for patients
Additional evidence suggests that tumor mutation burden (TMB) is a potential alternate and/or complementary biomarker to PD-L1 for the selection of patients for PD-(L)1 inhibitor–based therapy. Because Attention has now turned to identifying the appropriate immunotherapy-based treatment regimen for individual patients on the basis of a variety of factors; including the toxicity profile of each regimen; biomarkers predictive of treatment outcome, and, inevitably, patient preference.
The initial prospective demonstration that PD-L1 expression identifies an NSCLC patient population most likely to benefit fromanti–PD-1 therapy was the phase I KEYNOTE-001 (ClinicalTrials.gov identifier: NCT01295827) trial (Table 1). A PD-L1 expression cut point of 50% (22C3 antibody; Dako) predicted benefit with pembrolizumab.