At 5 Years, Over 30% of Patients in PACIFIC Had Stable NSCLC, Data Show

Lung cancer remains the leading cause of cancer death in the United States, projected to take 131,000 lives this year. But recent news in lung cancer has been positive—fewer new cases and fewer deaths—due to lower smoking rates, improved screening, and much better therapies.

Results presented this weekend at the 2021 Annual Meeting of theAmerican Society of Clinical Oncology (ASCO) showed the durability of a practice-changing therapy, as 5-year results for durvalumab (Imfinzi, AstraZeneca) showed that 43% of certain patients with non-small cell lung cancer (NSCLC) were alive after 5 years and 33% of who received the immunotherapy had no advancing disease.¹

Those rates are double or triple what would have been expected in the past, according to an investigator for the phase 3 trial, called PACIFIC. The trial evaluated the effectiveness of giving durvalumab for 1 year to patients with stage III NSCLC whose disease had not progressed after receiving concurrent platinum-based chemoradiotherapy.

David Spigel, MD, chief scientific officer at the Sarah Cannon Research Institute and an investigator 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 deter a tumor’s ability to work around the immune system.

Results from the abstract presented at ASCO showed:

• Overall, 709 of 713 randomized patients received either durvalumab or placebo; with 473 of 476 receiving the study drug and 236 of 237 getting placebo. The last patient completed treatment in May 2017. As of January 2021, median follow-up was 34.2 months.
• The 60-month overall survival (OS) rates were 42.9% for durvalumab compared with 33.4% for placebo. The stratified hazard 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 under way to boost lung cancer screening rates to catch cancer earlier. The US Preventive Services Task Force recently recommended starting screening for smokers or former smokers at age 50 instead of 55.

Although most patients present with NSCLC at stage III, multiple trials are ongoing to examine durvalumab at earlier stages of NSCLC, and the immunotherapy is also being tested in combination with other therapies in the stage 3 unresectable setting and in the neoadjuvant early-stage setting. If screenings rates improve and patients are tested at younger ages, more patients can be treated when NSCLC is a curable stage.

In presenting the results, Spigel said the 5-year data establish “a new benchmark for the standard of care in the unresectable stage III non-small-cell lung cancer setting.”

“Historically,” he said, “only 15% to 30% of these patients survived 5 years.”

When Another Option Is Needed

The practice-changing results from PACIFIC don’t apply to every patient with stage III unresectable NSCLC, according to Helen Ross, MD, a medical oncologist at Banner MD Anderson Cancer Center in Gilbert, Arizona, who presented results from the phase 2 AFT-16 study.²

"Unfortunately, many, if not most, of our unresectable stage III non-small cell lung cancer patients won't be eligible for adjuvant checkpoint inhibitor treatment,” she said. “We hypothesize that neoadjuvant atezolizumab given before chemoradiotherapy might allow more of our eligible patients to receive the potential benefit of a checkpoint inhibitor. And they would be able to continue adjuvant immune checkpoint inhibitor therapy after chemoradiotherapy, if they still had good performance status and no progression of disease.”

Ross explained the study schema:

• Patients with unresectable stage III A and B NSCLC received 4 cycles of atezolizumab, with restaging after cycles 2 and 4.
• Those who had not progressed went on chemoradiotherapy chest radiation with weekly carboplatin/paclitaxel, and were also eligible for standard consolidation therapy.
• Those who still had not progressed after restaging were eligible to complete 1 year of atezolizumab.
• Of the population of 64 patients with unresectable stage III disease, data from 62 who received at least 1 dose of atezolizumab were presented.

The average age of patients in the study was 63.9 years of age, 51.6% female, 77.4% white, 61.3% former smokers, 11.3% never smokers, and 56.5% ECOG PS = 1.

Results. The median PFS was 23.7 months, with PFS of 66% at 12 months and 57% at 18 months. OS was 84% at 18 months with median OS not estimable. Adverse events include 1 each grade 3 pneumonitis, pneumonia, and colitis, and 1 grade 4 Guillain-Barre syndrome.

Ross explained that the study team then undertook an exploratory analysis "to look at outcomes, including progression-free survival from the end of chemoradiotherapy to try to mirror the findings of the PACIFIC trial."

"Our progression-free survival at 12 and 18 months from the end of chemoradiotherapy was 78% and 72%, respectively," she said. "The PACIFIC trial reported progression-free survival at 12 months of 55.9%, and at 18 months of 44.2%.”

Based on these phase 2 findings, Ross said, "We think the neoadjuvant approach merits further study in unresectable stage III non-small cell lung cancer.”

References

1. Spigel D. Faivre-Finn C, Gray JE, et al. Five-year survival outcomes with durvalumab after chemoradiotherapy 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
2. Ross H, Kozono DE, Urbanic JJ. AFT-16: Phase II trial of neoadjuvant and adjuvant atezolizumab and chemoradiation (CRT) for 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