Radiotherapy Plus PD-L1 Inhibition/Chemo May Improve Outcomes in ES-SCLC

"The results showed that [the addition of thoracic radiotherapy] to standard first-line therapy (PD-L1 inhibitors plus chemotherapy) further improved PFS and OS," according to the authors of a study published in Radiation Oncology.

Thoracic radiotherapy yielded significant improvements in survival when combined with the PD-L1 inhibitors atezolizumab (Tecentriq) or durvalumab (Imfinzi) plus chemotherapy for patients with extensive-stage small-cell lung cancer (ES-SCLC), according to real-world data from a study published in Radiation Oncology.

The median progression-free survival (PFS) was 9.5 months with radiotherapy and 7.2 months without radiotherapy (HR, 0.59; 95% CI, 0.39-0.88; P = .009). The PFS rate at 6 months was 80.0% (95% CI, 65.8%-88.2%) with radiotherapy vs 61.4% (95% CI, 47.6%-73.7%) without (P = .041). Moreover, the 12-month rates were 31.6% (95% CI, 20.3%-45.4%) vs 14.0% (95% CI, 6.7%-26.4%), respectively (P = .026).

Median overall survival (OS) was 24.1 months in the radiotherapy group vs 18.5 months in the non-radiotherapy group (HR, 0.53; 95% CI; 0.31-0.89; P = .016). The 12-month OS rates were 73.7% (95% CI, 60.1%-84.1%) and 59.7% (95% CI 45.8–72.2) with vs without radiotherapy, respectively (P = .072). The 18-month survival rates were 45.6% (95% CI, 32.6%-59.2%) vs 35.1% (95% CI, 23.3%-48.9%), respectively (P = .252).

Investigators also found that the presence of baseline liver metastasis (HR, 2.58; 95% CI, 1.45-4.58) and 3 or more baseline metastases (HR, 1.86; 95% CI, 1.04-3.32) were risk factors associated with worse OS. Patients with baseline liver metastases had a median OS of 14.0 months compared with 23.8 months among those without (P <.001). Similarly, those with 3 or more metastases experienced a median OS of 14.5 months vs 23.0 months among those with fewer metastases (P = .009).

“Evidence from pre-clinical trials suggests that synergies may exist between immunotherapy and radiotherapy. Radiotherapy can remodel the tumor immune microenvironment, convert ‘cold’ into ‘hot’ tumors, thereby increasing the sensitivity of immunotherapy, and even improve the chances of an abscopal response,” the investigators wrote. “This real-world study was designed to examine the effect of the addition of [thoracic radiotherapy] to ES-SCLC [treatment] in the era of immunotherapy. The results showed that [the addition of thoracic radiotherapy] to standard first-line therapy (PD-L1 inhibitors plus chemotherapy) further improved PFS and OS.”

Investigators of this real-world study assessed outcomes across 211 patients from 12 sites in China enrolled between January 2019 and December 2021, grouped according to recept of thoracic radiotherapy. Investigators also performed propensity score matching with a 1:1 ratio.

Most patients were male (81.0%) and under 65 years old (63.0%). At diagnosis, most patients had an ECOG performance status of 0 to 1 (87.2%). The most commonly used PD-L1 inhibitor in this population was durvalumab (66.8%).

All patients received intravenous durvalumab or atezolizumab plus intravenous platinum-based chemotherapy, and 70 additionally received thoracic radiotherapy. Treatment occurred in 3-week cycles and was followed by maintenance therapy with duvalumab or atezolizumab every 3 weeks until disease progression, death, or unacceptable toxicity.

Both groups underwent a median of 6 cycles of chemotherapy. The radiotherapy group underwent a median of 7 (interquartile range [IQR], 5-10) total cycles of immunotherapy, and the non-radiotherapy group underwent a median of 6 (IQR, 5-8) cycles.

The primary end points of the study included PFS, OS, and safety profile. Secondary end points included the 12- and 18-month survival rates.

Clinically significant treatment-related pneumonitis affected 35.1% of those treated with radiotherapy and 15.8% of those treated without (P = .018). There was 1 death due to checkpoint inhibitor pneumonitis. In sum, 26.3% of patients receiving radiotherapy developed radiation pneumonitis, which was mostly grade 1 or 2.

“Few high-grade [AEs] occurred in the patients who were followed up, and most of them were mild, clinically manageable pneumonia,” the investigators concluded. “Further prospective studies in larger and more homogeneous patients are needed to validate these results.”

Reference

Peng J, Zhang L, Wang L, et al. Real-world outcomes of PD-L1 inhibitors combined with thoracic radiotherapy in the first-line treatment of extensive stage small cell lung cancer. Radiat Oncol. 2023;18(1):111. doi:10.1186/s13014-023-02308-2