One-third of NSCLC patients in PACIFIC are progression-free at 5 years, data shows
These rates are double or triple what would have been expected in the past, according to a researcher in the Phase 3 trial, called PACIFIC. The trial evaluated the efficacy of administering durvalumab for 1 year to patients with stage III NSCLC whose disease had not progressed after receiving concomitant platinum-based radiochemotherapy.
David Spigel, MD, scientific director of the Sarah Cannon Research Institute and researcher in the PACIFIC trial, said patients were included regardless of their PD-L1 status, even though durvalumab binds to PD-L1. The monoclonal antibody blocks the interaction with PD-1 and CD80 to prevent a tumor from bypassing the immune system.
The results of the summary presented to ASCO showed:
- Overall, 709 of 713 randomized patients received either durvalumab or placebo; with 473 of 476 receiving study drug and 236 of 237 receiving placebo. The last patient completed treatment in May 2017. In January 2021, the median follow-up was 34.2 months.
- The 60-month overall survival (OS) rates were 42.9% for durvalumab versus 33.4% for placebo. The stratified risk ratio (HR) was 0.72; 95% CI: 0.59-0.89.
- The 60-month progression-free survival (PFS) rates were 33.1% for durvalumab and 19.0% for placebo. The stratified HR was 0.55; 95% CI, 0.45-0.68.
Several initiatives are underway to increase lung cancer screening rates in order to detect cancer earlier. The US Prevention Services Task Force recently recommended starting screening for smokers or former smokers at age 50 instead of 55.
Although most patients have stage III NSCLC, several trials are underway to examine durvalumab in early stages of NSCLC, and immunotherapy is also being tested in conjunction with other therapies in stage 3 non resectable and in the neoadjuvant setting at an early stage. If screening rates improve and patients are tested at a younger age, more patients can be treated when NSCLC is a curable stage.
Presenting the results, Spigel said the 5-year data sets “a new benchmark for the standard of care in unresectable stage III non-small cell lung cancer.”
“Historically,” he said, “only 15-30% of these patients have survived 5 years.”
When another option is needed
Practice-changing PACIFIC findings may not apply to all patients with unresectable stage III NSCLC, according to Helen Ross, MD, medical oncologist at the Banner MD Anderson Cancer Center in Gilbert, Ariz., Who presented the results of the phase 2 AFT-16 study.2
“Unfortunately, many, if not most, of our unresectable stage III non-small cell lung cancer patients will not be eligible for adjuvant checkpoint inhibitor therapy,” she said. . patients eligible to receive the potential benefit of a checkpoint inhibitor. And they would be able to continue with adjuvant immune checkpoint inhibitor therapy after chemoradiation, if they still had good performance and no disease progression. “
Ross explained the outline of the study:
- Patients with unresectable stage III A and B NSCLC received 4 cycles of aezolizumab, with restaging after cycles 2 and 4.
- Those who had not progressed were subjected to chest radiotherapy by chemoradiation with carboplatin / paclitaxel weekly and were also eligible for standard consolidation therapy.
- Those who still had not progressed after restaging were eligible to complete 1 year of aezolizumab.
- From the population of 64 patients with unresectable stage III disease, data from 62 patients who received at least 1 dose of arezolizumab were presented.
The mean age of the study patients was 63.9 years, 51.6% female, 77.4% white, 61.3% former smoker, 11.3% non-smoker, and 56 , 5% ECOG PS = 1.
Results. The median PFS was 23.7 months, with a PFS of 66% at 12 months and 57% at 18 months. OS was 84% at 18 months with an unrecognizable median OS. Adverse events include grade 3 pneumonitis, pneumonia and colitis, and grade 4 Guillain-Barré syndrome.
Ross explained that the study team then undertook an exploratory analysis “to examine the results, including progression-free survival from the end of chemoradiotherapy to try to reflect the results of the PACIFIC trial.”
“Our progression-free survival at 12 and 18 months after the end of chemoradiation was 78% and 72%, respectively,” she said. “The PACIFIC trial reported 12-month progression-free survival of 55.9% and 18-month survival of 44.2%.”
Based on these Phase 2 results, Ross said: “We believe the neoadjuvant approach merits further study in unresectable stage III non-small cell lung cancer. “
- Spigel D. Faivre-Finn C, Gray JE, et al. Five-year survival results with durvalumab after chemoradiation in unresectable stage III NSCLC: an update from the PACIFIC trial. J Clin Oncol 2021; 39: (suppl 15; abstr 8511). DOI: 10.1200 / JCO.2021.39.15_suppl.8511
- Ross H, Kozono DE, Urbanic JJ. AFT-16: Phase II trial of aezolizumab and neoadjuvant adjuvant radiochemotherapy (CRT) in stage III non-small cell lung cancer (NSCLC). J Clin Oncol. 2021; 39: (suppl 15; abstr 8513). DOI: 10.1200 / JCO.2021.39.15_suppl.8513