Chemotherapy in combination with immune checkpoint inhibitors for the first-line treatment of patients with advanced non-small cell lung cancer: A systematic review and literature-based meta-analysis.

Abstract

e20565 Background: Checkpoint inhibitors plus platinum-based chemotherapy have shown superiority compared to chemotherapy alone as first-line therapy in advanced non–small cell lung carcinoma (NSCLC),To evaluate the relative benefit in term of Overall Survival (OS) and Progression-free Survival (PFS) of checkpoint inhibitors plus chemotherapy versus chemotherapy alone, overall and in subgroups defined by PDL1 expression we have performed a meta-analysis Methods: This meta-analysis searched PubMed and checked references of the selected English language articles to identify further eligible trials. Furthermore, proceedings of the main International meetings (American Society of Clinical Oncology [ASCO] annual meeting, European Society of Medical Oncology [ESMO] annual meeting, International Association for the Study of Lung Cancer [IASLC] World Conference on Lung Cancer), were searched from 2010 onwards for relevant abstracts. Data collection for this study took place from October 1 to October 24, 2018. Results: In total, 8 trials involving 4646 patients with advanced NSCLC, 3.314 (71%) and 1.332 (29%) with a non-squamous and squamous histology, respectively, were included in this meta-analysis. Four trials used atezolizumab, 3 pembrolizumab and 1 nivolumab, accounting for 2.985 (64%), 1.298 (28%) and 363 (8%) of patients, respectively. Checkpoint inhibitors plus chemotherapy were associated with prolonged OS, compared with chemotherapy in the ITT population (HR, 0.74; 95% CI, 0.64-0.87; p = 0.0002, with significant heterogeneity among trials). Within the PDL1 low group (1-49) there was a significant heterogeneity (p = 0.06) between type of drug and efficacy: the combination of chemotherapy plus pembrolizumab showed an OS benefit (HR, 0.56; 95% CI, 0.40-0.78; P< .00007) unlike the atezolizumab backbone trials (HR, 0.92; 95% CI, 0.62-1.37; P< 0.69). However, checkpoint inhibitors plus chemotherapy were associated with prolonged PFS in the ITT (HR, 0.61; 95% CI, 0.56-0.66; P < 0.00001) and across PDL1 subgroups. Conclusions: Checkpoint inhibitors plus chemotherapy compared with chemotherapy, are associated with significantly prolonged OS and PFS in first-line therapy in NSCLC. In the low PDL1 subgroups the benefit was statistically significant only in the pembrolizumab backbone trials.

Mechanisms of hyperprogressive disease after immune checkpoint inhibitor therapy: what we (don’t) know

“…In this case, the immunotherapy plus chemotherapy cohort demonstrated a superior anti-tumor effects for the entire duration of the follow-up [ 136 ]. Subsequent studies confirmed these initial findings [ 137 ], as also clearly shown in a recently published meta-analysis [ 138 ]. Indeed, Addeo et al collected the data from several randomized clinical trials in which chemotherapy was administered with ICIs as first-line treatment for metastatic NSCLC patients.…”

“…The Authors compared the PFS and OS of the chemotherapy alone group versus the chemotherapy plus immunotherapy arm. They found that in all considered clinical trials the combination of chemo/immunotherapy conferred an advantage in terms of OS and PFS compared to chemotherapy alone [ 138 ]. Apparently, no signs of HPD were detected in these trials.…”

“…In the majority of the clinical trials considered by Addeo et al [ 138 ], the chemotherapeutic drugs utilized are platinum or its derivatives that belong to the alkylating agents, a class of drugs able to cross-link DNA strands, thereby inhibiting DNA synthesis, eventually inducing the apoptosis of cancer cells. Beyond their cytotoxic activity, this type of chemotherapy also profoundly impacts on the immune TME.…”

Impact of performance status on non-small-cell lung cancer patients with a PD-L1 tumour proportion score ≥50% treated with front-line pembrolizumab

“…Representing 80-85% of all cases of lung cancer, non-smallcell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths worldwide [1]. Over the course of the last decade, the prognosis improved drastically, in large part thanks to the advent of immune checkpoint inhibitors (ICIs) [2,3].…”

Next-Generation Sequencing at High Sequencing Depth as a Tool to Study the Evolution of Metastasis Driven by Genetic Change Events of Lung Squamous Cell Carcinoma

“…Unfortunately, several studies have shown that only a subset of patients could benefit from this therapeutic protocol, such as patients with wild-type EGFR or negative ALK rearrangements (40,41). Moreover, in different PD-L1 expression subgroups, the benefit in OS and PFS is mixed (42).…”