PD-1 inhibitor combined with radiotherapy and GM-CSF as salvage therapy in patients with chemotherapy-refractory metastatic solid tumors.

Abstract

e15173 Background: Patients with refractory metastatic solid tumors have poor prognoses and few therapeutic options. The application of PD-1 inhibitor has led to a paradigm shift in the treatment of advanced cancer, but its efficacy as a monotherapy is limited. Previous evidence has shown that the anti-tumor effects might be reinforced when PD-1 inhibitor combines with radiotherapy or granulocyte macrophage-colony stimulating factor (GM-CSF). An exploratory study was conducted to assess the clinical efficacy and safety of PD-1 inhibitor combined with radiotherapy and GM-CSF (PRaG regimen) for the treatment of refractory patients. Methods: Participants had multimetastatic solid tumors progressing beyond at least first-line chemotherapy.They were treated with hyperfractionated radiotherapy (3 doses of 8Gy or 5 doses of 5Gy) for each metastatic site. On the second day after radiotherapy, PD-1 inhibitor 200 mg once was intravenously administered and GM-CSF 200 µg daily was subcutaneously injected for 2 weeks. This course was repeated every 3 weeks, targeting a second metastatic site. Triple-combination therapy. (PRaG regimen) was given for at least 2 cycles. After combination therapy, maintenance with PD-1 inhibitor was administered until disease progression or unacceptable toxicity. The main outcome measures included safety, toxicity, progression-free survival (PFS) and objective response rate (ORR) after three cycles of treatment. Results: A total of 16 patients were enrolled.The median number of metastatic lesions was 7.5(95%CI, 5.3 to 19.5) and the median sum of the longest diameter of all measurable lesions was 161.7mm (95%CI, 104.1 to 279.3mm).All patients completed two cycles or more of triple-combination therapy. The ORR was 20% and the median PFS was 3.3 months (95%CI, 2.3to 7.2months) at the time of evaluation. Treatment-related adverse events of any grade occurred in 13 (81%) patients, and grade 3 and higher adverse event like pneumonitis occurred in 2 (11.0%) patients. Conclusions: The PRaG regimen is well tolerated with acceptable toxicity. For patients with resistant metastatic solid tumors, low efficacy and high cytotoxicity are commonly observed in conventional therapy. With the new chemo-free PRaG regimen, myelosuppression was not observed and gastrointestinal side effects remained low. So, PRaG regimen is considered as a promising salvage treatment for patients with chemotherapy-refractory metastatic solid tumor. The suggested mechanism might involve radiosensitization of immunotherapy. Clinical trial information: ChiCTR1900020175 .