SAN ANTONIO — The continuing conundrum of clinical trials is how to assess their applicability to the patients actually seen in practice. Tackling one discrete treatment in non-small cell lung cancer (NSCLC), VA researchers studied whether veterans with NSCLC obtained the same benefit from durvalumab as participants in the pivotal PACIFIC trial did.
Durvalumab is a selective, human IgG1 monoclonal antibody that blocks programmed death ligand 1 (PD-L1) binding to programmed death 1 (PD-1) and CD80, which then enables T cells to recognize and attack tumor cells.
The phase 3 PACIFIC trial determined that durvalumab significantly extended survival in patients with stage III unresectable NSCLC who did not progress following concurrent chemoradiotherapy. At the last update, the five-year rate for progression-free survival was 33.1% for patients who received durvalumab vs. 19.0% for those who received a placebo. The five-year rate of overall survival was 42.9% for the durvalumab arm compared to 33.4% for the placebo arm.1
Researchers at the South Texas Veterans Healthcare System in San Antonio, the University of Texas at Austin, and others retrospectively analyzed patient records for all veterans with stage III unresectable NSCLC who were treated at a VHA facility between Jan. 1, 2017, and June 30, 2020. Patients were followed from initiation of durvalumab treatment until the earliest of the last VHA visit, loss to follow-up, death, or the end of the study.2
The team identified 935 veterans who met the criteria. Of the 340 with PD-L1 results, the tumors of 221 were PD-L1 positive and 119 had PD-L1 negative tumors. The groups were similar in terms of baseline characteristics and had a similar median number of durvalumab doses, 15 for those with positive tumors and 12 for those with negative tumors. Length of follow-up was also comparable between the groups, 31.5 months for the positive tumor group and 28.7 months for the negative tumor group.
The researchers estimated 12-month overall survival rates to be 84% for the positive tumor group and 89% for those with negative tumors. Twenty-four-month overall survival (OS) rates for patients with positive and negative tumors were 72% and 76%, respectively. While median overall survival was not reached in patients with PD-L1 positive tumors, it was 47 months in the group with PD-L1 negative tumors.
“Survival benefits with durvalumab were consistent with those reported in the PACIFIC trial, despite having worse baseline prognostic factors,” the investigators concluded. “Patients with PD-L1 positive and negative tumors experienced similar overall survival, including 12- and 24-month OS rates.”
- Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, Vansteenkiste JF, Garassino MC, Hui R, Quantin X, Rimner A, Wu YL, Özgüroğlu M, Lee KH, Kato T, de Wit M, Kurata T, Reck M, Cho BC, Senan S, Naidoo J, Mann H, Newton M, Thiyagarajah P, Antonia SJ. Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2022 Apr 20;40(12):1301-1311. doi: 10.1200/JCO.21.01308. Epub 2022 Feb 2. Erratum in: J Clin Oncol. 2022 Jun 10;40(17):1965.
- Burton EM, Moore A, NooruddinZ, Cotarla I, Simmons D, Davis L, Reveles KR, Datta P, Souza GR, Irabor OC, Franklin K, Jones X, Frei CR. Durvalumab outcomes for patients with PD-L1 positive and negative stage III unresectable non-small cell lung cancer treated at Veterans Health Administration facilities. 2023 ASCO annual meeting. June 2-6, 2023. Abstr. E18793. J Clin Oncol 41, 2023 (suppl 16; abstr
