Real-world effectiveness and tolerability of small-cell lung cancer (SCLC) treatments: A systematic literature review (SLR)

Abstract

Objectives: SCLC makes up approximately 15% of all lung carcinomas and is characterized by relatively aggressive spread and poorer prognosis compared to other lung cancers. Treatment options are limited, and their efficacy in randomized trials is poor, whilst outcomes in clinical practice remain unclear. The aim of this study was to assess the real-world effectiveness and tolerability of SCLC treatments.

Methods: An SLR was conducted across nine databases accessed through OVID, capturing observational, non-randomized studies published between 01/2006-11/2018. In total, 554 abstracts were retrieved and systematically screened for eligibility. The eligible publications included effectiveness and tolerability data from adult SCLC patients (at any line of therapy). Additional grey literature searches were conducted.

Results: Forty-three publications were included in this review-data from first-line therapies were captured most often (n = 32), while data from second (n = 14) and third line (n = 7) and beyond (n = 7) were less frequent. The publications reported primarily on chemotherapy/radiotherapy. The majority of publications lacked robustness and only 14/43 conducted statistical analyses or controlled for bias. Median OS for the largest SCLC populations were 9.6 months at first line (n = 23,535) and 4.9 months at second line (n = 254) for treatment with chemotherapy, and 4.7 months at third line (n = 120) for predominantly platinum-based chemotherapy or cyclophosphamide/adriamycin/vincristine. Hematologic toxicities (such as neutropenia, thrombocytopenia and anemia) were the most frequently reported TRAEs (n = 9).

Conclusions: Real-world treatment effectiveness and tolerability data were fragmented and inconsistently reported, and available publications were primarily of poor quality and lacked statistical analyses. This SLR showed limited treatment options and poor OS in SCLC, with no treatment option being clearly superior. TRAEs additionally increased the burden of this already challenging disease. Recent data suggest real-world outcomes are even poorer that those reported in clinical trials, and that novel therapies are needed to offer new treatment options for patients.

Fig 1. PRISMA flow diagram of captured publications.

*Other reasons for exclusion at full-text screening stage were small population size (<20 SCLC patients) or duplicating results that had already been captured. **“Other” grey literature items were sourced through internet searches. HRQoL = health-related quality of life; n = number of records; PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Fig 2. Median OS (months) at first line[28, 30, 34, 35, 37, 38, 44, 51].

*One patient received radiotherapy only. **Three patients received radiotherapy only. CT = chemotherapy; ERCC1- = excision repair cross-complementation group 1 negative; ERCC1+ = excision repair cross-complementation group 1 gene positive; n = number of patients; NA = not available; OS = overall survival; PCI = prophylactic cranial irradiation; pts = patients; TRT = thoracic radiotherapy.

Fig 3. Most common TRAEs reported for patients treated with SCLC therapies[30, 35, 42, 51].

Note: Presented TRAEs exceed 5% or lead to discontinuation. *These TRAEs were specified as grade 3–4. **These outcomes refer to febrile neutropenia specifically. CT = chemotherapy; n = number of patients; pts = patients; SCLC = small-cell lung cancer; TRAEs = treatment-related adverse events; TRT = thoracic radiotherapy.

Fig 4. Median OS (months) at second line[36, 43, 62, 68].

CM = cranial metastasis; CT = chemotherapy; n = number of patients; OS = overall survival; pts = patients.

Fig 5. Median OS (months) at third line[15, 49, 52, 60, 63].

2L = second line; CAV = cyclophosphamide, doxorubicin and vincristine; CR = complete response; CT = chemotherapy; n = number of patients; OS = overall survival; PD = progressive disease; PR = partial response; pts = patients; SD = stable disease.