Real-World Study Confirms Atezolizumab Plus Chemotherapy Is Feasible and Safe First-Line Therapy for Extensive-Stage Small Cell Lung Cancer
核心洞察
A retrospective real-world study of 48 patients found atezolizumab plus carboplatin-etoposide achieved a median progression-free survival of 5.8 months and overall survival of 7.1 months in extensive-stage small cell lung cancer (搜索).
The regimen demonstrated a satisfactory safety profile, with grade 3–4 adverse events occurring in 60.4% of patients, most frequently during the induction phase.
Compared with the pivotal IMpower133 trial, the real-world cohort showed improved PFS but poorer OS, likely reflecting a more heterogeneous population with worse performance status and more brain metastases.
A real-world, retrospective study conducted at a third-level hospital in Spain found that atezolizumab in combination with carboplatin and etoposide is feasible and safe as first-line therapy for extensive-stage small cell lung cancer (搜索) (ES-SCLC) in routine clinical practice. The analysis, which included all 48 ES-SCLC patients treated with the regimen between March 2022 and May 2024, reported a median progression-free survival (PFS) of 5.8 months (95% CI: 4.8–6.7 months) and a median overall survival (OS) of 7.1 months (95% CI: 3.6–10.7 months).
The study aimed to assess the effectiveness and safety of the atezolizumab–carboplatin–etoposide regimen outside the controlled setting of clinical trials, where patient populations are often highly selected. In routine practice, patients may present with poor performance status, relevant comorbidities, or active metastases that are not always represented in pivotal studies.
Patient Population and Treatment
The cohort had a mean age of 66.4 years (standard deviation 6.5), with 56.3% male patients. Eastern Cooperative Oncology Group (ECOG) performance status was 0 in 27.1% of patients, 1 in 58.3%, and 2 in 14.6%. Metastases at diagnosis were present in 89.6% of patients, including brain metastases in 29.2%. Most patients (93.8%) received the regimen as first-line therapy.
Patients received a median of 4 cycles (range 2–6) of atezolizumab plus carboplatin and etoposide, followed by a median of three atezolizumab maintenance doses (range 0–33). The dosing regimen consisted of atezolizumab at a fixed dose of 1200 mg intravenously on Day 1 of each 21-day cycle, carboplatin at an area under the curve of 5 mg/ml·min intravenously on Day 1, and etoposide at 100 mg/m² intravenously from Day 1 to Day 3, followed by maintenance atezolizumab at 1200 mg intravenously every 3 weeks. The median total treatment duration was 4.4 months (range 0.8–26.8), with five patients (10.4%) receiving treatment for more than 12 months.
Efficacy Outcomes
The objective response rate (ORR) was 58.3%, comprising complete responses in 4 patients (8.3%) and partial responses in 24 patients (50.0%). Stable disease was observed in 8 patients (16.7%), progressive disease in 5 (10.4%), and 7 patients (14.6%) were not assessable. The median time to best response was 3.0 months (range 0.8–11.8), and the median duration of response was 3.6 months (range 0.2–24.0).
A total of 41 patients (85.4%) experienced disease progression or death, and 37 patients (77.1%) did not survive by study completion. At the end of follow-up, 22.9% (n = 11) of patients had survived, of whom 14.6% (n = 7) were still receiving treatment.
ECOG performance status significantly influenced outcomes. Patients with ECOG 0 exhibited longer PFS compared with ECOG 1 and 2 cases (7.3 months versus 5.1 and 3.7 months, respectively; p = 0.004 and p = 0.005). OS was also higher among ECOG 0 patients compared with ECOG 1 and 2 patients (18.6 months versus 6.7 and 5 months, respectively; p < 0.001 and p = 0.003), with no significant difference between ECOG 1 and 2 (p = 0.057).
The number of maintenance atezolizumab doses also correlated with survival. Patients who received ≤2 doses (n = 22, 45.8%) had an OS of 4.5 months, significantly lower than patients who received more than 2 doses (n = 26, 54.2%; 17.1 months; p < 0.001). PFS was likewise higher in the latter group (3.6 versus 7.2 months; p < 0.001).
No significant association was observed between the presence of brain metastases at diagnosis and PFS or OS, although OS tended to improve in patients free of brain metastases (9.2 months versus 5.3 months; p = 0.06).
Safety Profile
Among the 48 patients, 29 (60.4%) developed grade 3–4 adverse events (AEs), including 27 (67.5%) with grade-3 events and 13 (32.5%) with grade-4 events. The most common grade 3–4 AEs were neutropenia (41.6%), anemia (10.4%), and thrombocytopenia (8.3%). Neutropenic fever occurred in 2 patients (4.2%), and asthenia and hypomagnesemia each occurred in 1 patient (2.1%).
Most AEs occurred during the induction phase with the chemotherapy–atezolizumab combination, whereas only 4 patients (13.8%) developed AEs during maintenance therapy with atezolizumab. Treatment was discontinued due to toxicity in two cases (4.2%): one for recurrent grade 3–4 thrombocytopenia and another for grade 4 anemia.
Immune-mediated grade 3–4 AEs occurred in 3 patients (6.25%), including immune-mediated diabetes mellitus, immune-mediated mucositis, and immune-mediated pancreatitis.
Comparison with the IMpower133 Trial
The phase III IMpower133 trial, which established atezolizumab plus carboplatin and etoposide as the standard of care for ES-SCLC, reported a PFS of 5.2 months (95% CI: 4.4–5.6 months) and an OS of 12.3 months (95% CI: 10.8–15.8 months). Compared with the IMpower133 population, the real-world cohort had a slightly higher median age (66.1 versus 64 years) and a lower proportion of male participants (56.3% versus 65%).
Notably, the real-world study included a higher proportion of patients with characteristics associated with poorer outcomes, including an ECOG score of 2 or higher (14.6% versus none in IMpower133) and a higher prevalence of brain metastases (29.2% versus 9%). The IMpower133 trial included only treated and stable brain metastases, whereas the real-world study also included untreated metastases.
The median PFS in the real-world study was slightly higher than in IMpower133 (5.8 versus 5.2 months), while OS was substantially poorer (7.1 versus 12.3 months). The ORR was comparable between the two studies (58.0% versus 60.2%), suggesting that the regimen preserves efficacy even in a more heterogeneous, real-world setting.
Regarding safety, grade 3–4 neutropenia was more frequent in the real-world population (41.6% versus 22.7%), while anemia and thrombocytopenia were slightly lower (10.4% versus 14.1% and 8.3% versus 10.1%, respectively). Grade 3–4 immune-mediated AEs were less common (6.3% versus 39.9%).
Study Limitations
The authors acknowledged several limitations, including the single-center design, small sample size (48 patients), and the retrospective nature of data collection, which limited the availability of some data—particularly AE-related information. The short follow-up period (median 7.6 months) may also have influenced results. The authors called for larger, prospective, multicentric studies with longer follow-up to confirm the duration of response, toxicity, and effects of this regimen on long-term survival.