Durvalumab Confirmed Beneficial After NSCLC Chemoradiotherapy

The benefits of durvalumab have been confirmed in a new analysis that compared patient characteristics, treatment patterns, and outcomes between those who initiated adjuvant treatment with the anti–PD-L1 antibody after chemoradiotherapy (CRT) for non–small cell lung cancer (NSCLC) and patients who completed their CRT and did not subsequently receive durvalumab.

These findings from the retrospective SPOTLIGHT study, published in JAMA Network Open,¹ follow in the footsteps of the PACIFIC trial (NCT02125461), which established durvalumab post CRT as standard-of-care treatment for patients with unresectable stage III NSCLC. PACIFIC investigated the agent MEDI4736, now known as durvalumab, among 713 patients with documented NSCLC who had received at least 2 cycles of platinum-based chemotherapy and concurrent radiation therapy; outcomes were compared vs those who received placebo.²

The investigators stated there is a critical need have a better understanding of durvalumab’s impact on US clinical practices.

Patients receiving durvalumab in the SPOTLIGHT analysis had a 64% reduced risk of death or disease progression | Image Credit: wladimir1804 - stock.adobe.com

Deidentified patient-level data for the present analysis came from US Flatiron Health for patients whose NSCLC was diagnosed on or after January 1, 2011; who had at least 2 visit for the cancer after their diagnosis; and who received CRT. The cutoff to begin durvalumab treatment was June 30, 2019, so the investigators could have 15 or more months of follow-up. Primary outcomes of interest were time to first subsequent therapy or death (TFST) and time to distant metastasis or death (TTDM), and exploratory outcomes were progression-free survival (PFS) and overall survival (OS).

There were 332 patients in the durvalumab cohort and 137 in the nondurvalumab cohort. Median (IQR) ages were 67.5 (60.8-74.0) years and 70 (64-75) years, respectively. Most patients in each group were male patients (56.3% and 65.0%, respectively), of a White ethnicity (80.6% and 75.6%), had a smoking history (95.2% and 96.4%), and had Eastern Cooperative Oncology Group performance status of 0 through 1 (90.9% and 81.5%). In addition, 95% were treated at community oncology practices.

Regarding the primary outcomes of interest, median PFS was 17.5 (95% CI, 13.6-24.8) months in the durvalumab cohort and 7.6 (95%CI, 5.2-9.8) months in the nondurvalumab cohort. Length of OS was not reached for the durvalumab cohort and 19.4 (95%CI, 11.7-24.0) months for the nondurvalumab cohort.

The positive findings for durvalumab continued with TFST, which was not reached; however, this was 8.3 (95% CI, 4.8-11.8) months for those who did not receive durvalumab. TTDM was also not reached for durvalumab but was 11.3 (95% CI, 6.4-14.5) months in the nondurvalumab cohort.

Median durations of CRT were close to equal in the patient groups, with those receiving durvalumab undergoing CRT for a median 1.6 (1.4-1.8) months and those not receiving durvalumab undergoing CRT for 1.5 (1.4-1.8) months. Patients received durvalumab for median 9.5 (95% CI, 1.8-10.6) months before discontinuing the regimen.

A Cox regression analysis then looked at the outcome of no disease progression and concurrent CRT, and there was a 64% (HR, 0.36; 95% CI, 0.26-0.51) reduced risk of death or disease progression associated with durvalumab treatment and a 73% (HR, 0.27; 95% CI, 0.16-0.43) reduced risk of death alone when prior platinum agent and patient characteristics were considered. Patients received a median 16.5 (1-60) durvalumab infusions. The primary reason for durvalumab discontinuation was physician assessment (40.1%).

Earlier this year, durvalumab also showed benefit in a study that investigated its effects among patients 70 years and older vs younger than 70 years.The agent was deemed equally effective for both patient groups who had been underrepresented in the pivotal PACIFIC trial.³

Of their SPOTLIGHT findings, the investigators highlight their consistency with the PACIFIC trial—that durvalumab has potential to be effective in everyday US clinical practice—and with the PACIFIC-R trial (NCT03798535), which evaluated durvalumab’s effectiveness in a non-US cohort.

Potential limitations on their findings are the study’s retrospective observational design, that the patient data came mainly from Flatiron network community practices, and lack of a detailed analysis on toxicity.

“Further investigation of durvalumab administration patterns (eg, factors leading to the decision not to administer durvalumab),” the authors concluded, “is warranted to explain why patients did not receive durvalumab after its approval.”

References

1. Mooradian MJ, Cai L, Wang A, Qiao Y, Chander P, Whitaker RM. Durvalumab after chemoradiotherapy in patients with unresectable stage III non–small cell lung cancer. JAMA Netw Open. 2024;7(4):e247542. doi:10.1001/jamanetworkopen.2024.7542

2. A global study to assess the effects of MEDI4736 following concurrent chemoradiation in patients with stage III unresectable non–small cell lung cancer (PACIFIC). ClinicalTrials.gov. Updated October 10, 2023. Accessed April 26, 2024. https://clinicaltrials.gov/study/NCT02125461

3. Shaw M. Durvalulmab consolidation therapy shows promise in elderly patients with stage III NSCLC. The American Journal of Managed Care. February 12, 2024. Accessed April 26, 2024. https://www.ajmc.com/view/durvalumab-consolidation-therapy-shows-promise-in-elderly-patients-with-stage-iii-nsclc