In a phase 2 study, the combination of olaparib with immune checkpoint inhibitor durvalumab failed to meet the prespecified efficacy end point in patients with relapsed small cell lung cancer (SCLC).1

“Poly (ADP-ribose) polymerase 1 (PARP1) is highly expressed in SCLC and PARP inhibitors have shown antitumor activity in both SCLC preclinical models and patients,” the study researchers wrote. “Preclinical observations suggest that [the] combination of immune checkpoint blockade with PARP inhibition may be an effective therapeutic strategy.”

To test this, investigators treated 24 patients with durvalumab 1500 mg every 4 weeks plus olaparib 300 mg twice daily. The primary outcome was overall response rate.

Related Articles

Only 19 patients were evaluable for response. Of these, 2 patients (10.5%) had a confirmed partial or complete response to treatment, including 1 patient with EGFR-transformed SCLC. The clinical benefit was 21.1%, combining those patients with response or stable disease of 8 months or longer.

Median progression-free survival was 1.8 months, with a 6-month progression-free survival probability of 20.0%. Median overall survival was 4.1 months, with a median 6-month overall survival of 37.1%.

Almost half (45%) of patients had a grade 3/4 treatment-related adverse event including anemia, lymphopenia, thrombocytopenia, and hypophosphatemia.

The researchers noted that tumor response occurred in all patients where pretreatment tumors were T-cell–inflamed.

“Tumor CD8+ T-cell infiltration has been linked to antitumor activity in patients with advanced melanoma and NSCLC treated with immune checkpoint inhibitors,” the researchers wrote. “Our observation extends these findings to relapsed SCLC and suggests that a preexisting CD8+ T-cell response may be predictive of benefit from immune checkpoint inhibitor-based therapies in SCLC.”

Reference

  1. Thomas A, Vilimas R, Trindade C, et al. Durvalumab in combination with olaparib in patients with relapsed small cell lung cancer: results from a phase II study. Journal of Thoracic Oncology. 2019;doi:10.1016/j.jtho.2019.04.026.