Simultaneous Durvalumab and Platinum-Based Chemoradiotherapy in Unresectable Stage III Non–Small Cell Lung Cancer: The Phase III PACIFIC-2 Study

Author(s): Jeffrey D. Bradley, MD¹; Shunichi Sugawara, MD, PhD²; Ki Hyeong Lee, MD, PhD³; Gyula Ostoros, MD, PhD⁴; Ahmet Demirkazik, MD⁵; Milada Zemanova, MD, PhD⁶; Virote Sriuranpong, MD, PhD⁷; Ana Caroline Zimmer Gelatti, MD⁸; Juliana Janoski de Menezes, MD⁹; Bogdan Zurawski, MD, PhD¹⁰; Michael Newton, PharmD¹¹; Pratibha Chander, MPH¹¹; Nan Jia, PhD¹²; Zofia F. Bielecka, PhD¹³; Mustafa Özgüroğlu, MD¹⁴; on behalf of the PACIFIC-2 Investigators;

Source: DOI: 10.1200/JCO-25-00036

Dr. Anjan Patel's Thoughts

PACIFIC-2 was a phase III trial testing durva given concurrently with cCRT (and continued as consolidation) versus placebo + cCRT in unresectable stage III NSCLC, and it did not meet its primary endpoint. The overall response rate (ORR) was essentially identical (60.7% vs 60.6%), and pneumonitis rates were similar (any grade 28.8% vs 28.7%; grade ≥3: 4.6% vs 5.6%), but adverse events (AEs) leading to discontinuation and fatal AEs were higher with durva (25.6% vs 12.0%; 13.7% vs 10.2%), especially early on. Starting IO up front with cCRT didn’t improve outcomes and added early toxicity—consolidation durva after cCRT is still the way to go.

PURPOSE

Immunotherapy targeting PD-L1 improves outcomes in patients with unresectable stage III non–small cell lung cancer (NSCLC) and no progression after definitive, concurrent chemoradiotherapy (cCRT). Earlier administration of immunotherapy, simultaneously with cCRT, may improve outcomes further.

METHODS

Eligible patients were randomly assigned (2:1) to receive either durvalumab or placebo administered from the start of cCRT. Patients without progression after completing cCRT received consolidation durvalumab or placebo (per initial random assignment) until progression. The primary end point was progression-free survival (PFS) by blinded independent central review. Key secondary end points included objective response rate (ORR), overall survival (OS), the proportion of patients alive 24 months (OS24), and safety.

RESULTS

In total, 328 patients were randomly assigned to receive durvalumab (n = 219) or placebo (n = 109). There was no statistically significant difference with durvalumab versus placebo in PFS (hazard ratio [HR], 0.85 [95% CI, 0.65 to 1.12]; P = .247) or OS (HR, 1.03 [95% CI, 0.78 to 1.39]; P = .823); OS24 was 58.4% versus 59.5%, respectively. Confirmed ORR was 60.7% with durvalumab versus 60.6% with placebo (difference, 0.2% [95% CI, −15.2 to 16.3%]; P = .976). With durvalumab versus placebo, respectively, maximum grade 3 or 4 adverse events (AEs) occurred in 53.4% versus 59.3% of patients, pneumonitis or radiation pneumonitis (group term) in 28.8% (grade ≥3: 4.6%) versus 28.7% (grade ≥3: 5.6%), AEs leading to discontinuation of durvalumab or placebo in 25.6% versus 12.0%, and fatal AEs in 13.7% versus 10.2%.

CONCLUSION

Among patients with unresectable stage III NSCLC, durvalumab administered from the start of cCRT failed to demonstrate additional benefit compared with cCRT plus placebo. Consolidation durvalumab following definitive cCRT remains the standard of care in this setting.

Author Affiliations

¹Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA; ²Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai City, Japan; ³Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Republic of Korea; ⁴Koranyi National Institute for TB and Pulmonology, Budapest, Hungary; ⁵School of Medicine, Ankara University, Ankara, Turkey; ⁶Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic; ⁷Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; ⁸Hospital São Lucas PUC/RS, Grupo Oncoclínicas, Porto Alegre, Brazil; ⁹Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil; ¹⁰Department of Outpatient Chemotherapy, Professor Franciszek Lukaszczyk Oncology Center, Bydgoszcz, Poland; ¹¹AstraZeneca, Gaithersburg, MD; ¹²AstraZeneca, Waltham, MA; ¹³AstraZeneca, Warsaw, Poland; ¹⁴Istanbul University—Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Istanbul, Turkey

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