Imfinzi (durvalumab) when given as a consolidation treatment after chemoradiation significantly improved survival compared to a placebo (inactive drug) for patients with limited-stage small cell lung cancer (LS-SCLC), according to an analysis of the ongoing phase 3 ADRIATIC study.
Consolidation therapy is given after treatment to kill off any remaining cancer cells and prevent the disease from coming back. This improvement, according to investigators, is the first major advancement this patient population has seen in decades.
The findings, which were shared during a press briefing at the 2024 ASCO Annual Meeting, revealed that at a median follow-up of 37.2 months (range, 0.1 to 60.9), the median overall survival (OS; time from treatment until death of any cause) with Imfinzi (264 patients) was 55.9 months compared to 33.4 months with placebo (266 patients), translating to a 27% reduction in the risk of death.
Moreover, at a median follow-up of 27.6 months (range, 0.0 to 55.8), the median progression-free survival (PFS; time from treatment until disease worsening) was 16.6 months with Imfinzi versus 9.2 months with placebo, equating to a 24% reduction in the risk of disease progression or death.
“In conclusion, [Imfinzi] as consolidation treatment after concurrent chemoradiotherapy demonstrated statistically significant and clinically meaningful improvement in both OS and PFS compared with placebo in patients with LS-SCLC,” Dr. David R. Spigel, medical oncologist and chief scientific officer at Sarah Cannon Research Institute, in Nashville, Tennessee, said in a presentation of the data.
Consolidation Imfinzi to Be New Standard of Care
“The treatment benefit was generally consistent across predefined subgroups for both OS and PFS, and consolidation treatment up to two years was well tolerated…Consolidation [Imfinzi] will become the new standard of care for patients with LS-SCLC following chemoradiotherapy.”
The current standard of care for patients with LS-SCLC is concurrent chemoradiotherapy, meaning that chemotherapy and radiation are given simultaneously. However, most patients will relapse within two years of treatment, and the five-year survival rate only ranges from 29% to 34%. The rationale for the ADRIATIC trial was supported by findings from the pivotal phase 3 PACIFIC and CASPIAN studies, according to Spigel.
“The PACIFIC study looked at the role of [Imfinzi] after concurrent chemoradiotherapy for stage 3 non–small cell lung cancer, and that demonstrated an improvement in both OS and PFS,” he reported. “But the CASPIAN study also looked at [Imfinzi] with platinum etoposide chemotherapy, and that showed an improvement in OS when used in newly diagnosed patients with extensive-stage SCLC.”
With ADRIATIC, investigators are examining the role of the PD-L1 antibody, Imfinzi, with or without the CTLA-4 antibody, Imjudo (tremelimumab), as consolidation therapy after concurrent chemoradiation in those with LS-SCLC. At the 2024 ASCO Annual Meeting, Spigel shared data focused on comparing Imfinzi with placebo in this population. Data regarding the combination will be shared at a later date, he noted.
About the ADRIATIC Study
The double-blind, placebo-controlled, multicenter, international, phase 3 ADRIATIC study enrolled patient with stage 1 to 3 LS-SCLC, including those with stage 1/2 disease that is not eligible for surgery. Patients were required to have a World Health Organization performance status of 0 or 1, meaning that they either have no restrictions or are restricted in strenuous activity, and they could not have progressed after concurrent chemoradiation. Prophylactic cranial irradiation (PCI; radiation to the brain to prevent the spread of cancer in the brain) was permitted prior to randomization.
Seven-hundred thirty patients were randomly assigned to one of three arms:
- Single-agent Imfinzi at 1,500 mg every four weeks
- Placebo every four weeks
- Imfinzi at 1,500 mg every four weeks plus Imjudo at 75 mg every four weeks for four doses, followed by Imfinzi monotherapy given at 1,500 mg every four weeks.
Treatment continued until investigator-determined disease progression, unacceptable side effetcs or up to 24 months. Patient data was grouped based on multiple factors, including disease stage (1/2 versus 3) and whether patients received PCI.
The two goals of the trial were OS and PFS by blinded independent central review (BICR; a panel of experts unassociated with the study who are unaware of what treatment each patient received) and RECIST 1.1 criteria (a criteria used to determine if tumors shrink, grow or disappear) with Imfinzi alone versus placebo. Key secondary end points are focused on examining the OS and PFS by BICR and RECIST 1.1 criteria with Imfinzi plus Imjuso versus placebo. Safety and quality-of-life analyses were also performed, Spigel said.
Additional efficacy data showed that at the three-year landmark analysis, the OS rates were 56.5% with Imfinzi versus 47.6% with placebo. At the two-year landmark analysis, the PFS rate with Imfinzi was 46.2% versus 34.2% with placebo.
Regarding safety, any-grade, all-cause side effects occurred in 94.3% of evaluable patients who received Imfinzi (262 patients) versus 88.3% of those given placebo (265 patients); these effects were sever to life-threatening (grade 3/4) for 24.4% and 24.2% of patients, respectively. Serious side effects occurred in 29.8% of those given Imfinzi versus 24.2% of those given placebo.
Side effects led to treatment discontinuation for 16.4% and 10.6% of patients, respectively; they resulted in death for 2.7% and 1.9% of patients, respectively. Specifically, two patients on the Imfinzi arm experienced treatment-related side effect that proved fatal; causes of death were encephalopathy (brain dysfunction) and pneumonitis (lung inflammation).
Moreover, any-grade immune-related side effects were reported in 32.1% of those in the Imfinzi arm versus 10.2% of those in the placebo arm; these effects were grade 3 or 4 in severity for 5.3% and 1.5% of patients, respectively. Any-grade pneumonitis or radiation pneumonitis occurred in 38.2% of those who received Imfinzi versus 30.2% of those given placebo; these effects were grade 3/4 for 3.1% and 2.6% of patients, respectively.
“This study [showed that (Imfinzi)] had a very good safety profile. Looking at grade 3/4 [side effects), these [rates] were nearly identical in each arm, at 24%,” Spigel concluded. “…The safety signals were really consistent with what is already known for monotherapy with [Imfinzi] following concurrent chemoradiation.”
After the presentation, Dr. Lauren A. Byers, ASCO expert and professor and thoracic section chief in the Department of Thoracic-Head & Neck Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, commented on the study and its significance: “SCLC is one of the most aggressive types of lung cancer. As you heard from Dr. Spigel, the treatment for patients with LS-SCLC who are being treated with the intent of cure has not changed since the 1980s. The ADRIATIC trial is a landmark study and provides a new SOC with the addition of immunotherapy for patients with early-stage SCLC who are being treated with a goal of curing their cancer.”
She added, “It’s also an important study because of the magnitude of benefit that patients received with the addition of [Imfinzi] consolidation, with an average improvement in OS around two years. This is in contrast to many clinical trials in SCLC, where often, the benefit may only be measured in months. Similar to other lung cancers, and you’ve heard about many advances related to personalization of lung cancer treatment for patients, we now know that SCLCs are really different types of lung cancers. And so, I think one important next step will be to understand who's benefiting the most with the addition of [Imfinzi] and how can we start thinking about personalizing treatment for the different subtypes of SCLC to further build on this and continue to make progress for these patients.”
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