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Francesco Perrone
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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-52 - BR-34- Randomized Trial of Durvalumab & Tremelimumab +/- Platinum Chemotherapy in Patients with Metastatic Squamous or Non-Squamous NSCLC (ID 11791)
16:45 - 18:00 | Author(s): Francesco Perrone
- Abstract
Background
Background- Immunotherapy improves survival of patients with non-small cell lung cancer (NSCLC). Current clinical trials are studying various combinations of PD-1/PD-L1 inhibitors and CTLA-4 agents with or without chemotherapy, to enhance treatment efficacy. This trial will determine the effects of adding platinum chemotherapy to combination of check point blockade with durvalumab and tremelimumab in the first line treatment of advanced non-small cell lung cancer.
a9ded1e5ce5d75814730bb4caaf49419 Method
Method- BR-34 is a CCTG led randomized proof-of-concept trial of durvalumab and tremelimumab, with or without platinum-based chemotherapy in patients with metastatic squamous or non-squamous NSCLC. Patients who have histologically confirmed Stage IV NSCLC and wild type EGFR and ALK, PDL-1 unselected, with measurable disease by RECIST 1.1, and available tissue for biomarker testing are eligible and are stratified by stage, histology and smoking status. Primary end point is overall survival. Secondary end points include progression free survival at 1 year, overall response rate, quality of life, cost effectiveness and correlative studies on tissue and blood (including PD-L1, tumour mutation burden and cell-free DNA) with outcomes and response, and PFS by iRECIST (exploratory). In total 300 patients will be recruited from Canada, Australia and Italy. Arm A will receive 4 cycles of fixed doses of tremelimumab (T) 75 mg plus durvalumab (D) 1500 mg every 28 days IV, followed by durvalumab (D) maintenance and Arm B will receive standard platinum-doublet chemotherapy in combination with T+D every 21 days for 4 cycles, followed by maintenance D (with pemetrexed for those with non-squamous histology), until progression.
4c3880bb027f159e801041b1021e88e8 Result
Results- BR-34 was initiated in February 2017 in Canada and total 150 patients have been randomized as of April 2018, including 137 from Canada and 13 from Australia. 28 sites are open to accrual in Canada, 15 in Australia the trial will soon be opened in Italy.
8eea62084ca7e541d918e823422bd82e Conclusion
Conclusion- At the current rate of accrual, the CCTG BR-34 trial should be fully accrued by Q1 2019. This is the first randomized trial of combination checkpoint blockade +/- platinum-doublet chemotherapy in advanced non-small cell lung cancer.
Acknowledgements: BR-34 is an academic, co-operative group trial led by Canadian Cancer Trials Group (CCTG) in collaboration with ALTG and NHMRC Clinical Trials Centre, with support from AstraZeneca and Canadian cancer society. NCT03057106
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P1.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 948)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.16-04 - Outcomes of Patients < 70 or ≥70 Years of Age in PACIFIC (ID 13012)
16:45 - 18:00 | Author(s): Francesco Perrone
- Abstract
Background
In the Phase 3 PACIFIC study of durvalumab versus placebo in patients with stage III, unresectable NSCLC without progression after concurrent chemoradiotherapy (cCRT), the co-primary endpoint PFS was significantly longer with durvalumab (stratified HR 0.52, 95% CI, 0.42–0.65; P<0.0001). In a prespecified analysis, PFS benefit with durvalumab was observed regardless of a 65-year age cutoff. However, median age at NSCLC diagnosis is 70 (CA Cancer J Clin, 2014). We therefore performed subgroup analyses to explore outcomes using a 70-year age cutoff.
a9ded1e5ce5d75814730bb4caaf49419 Method
PACIFIC (NCT02125461) was a Phase 3, randomized, double-blind, all-comers study of patients with WHO PS 0/1 who did not progress following ≥2 cycles of platinum-based cCRT. Patients were stratified by age, sex, and smoking history and randomized (2:1) 1–42 days after cCRT to receive durvalumab 10 mg/kg IV Q2W or placebo up to 12 months. Co-primary endpoints were PFS (BICR, RECIST v1.1) and OS (not available). Secondary endpoints included ORR, time to death/distant metastasis (TTDM), and safety. Between-treatment endpoint comparisons were performed for patients <70 and ≥70 years.
4c3880bb027f159e801041b1021e88e8 Result
As of Feb 13, 2017, 713 patients were randomized; 78% and 22% were <70 and ≥70 years, respectively. Baseline patient and tumor characteristics were generally well balanced across subgroups. However, patients ≥70 were more likely to be male, have PS 1, and, within the placebo arm, to be Asian. Older patients more commonly received carboplatin-based CT than younger patients. Durvalumab demonstrated PFS benefit compared with placebo, regardless if patients were <70 years (median 16.9 vs 5.6 months, HR=0.53, 95% CI: 0.42–0.67) or ≥70 years (median 12.3 vs 6.1 months, HR=0.62, 95% CI: 0.41–0.95). Durvalumab improved TTDM (<70 years: HR=0.53, 95% CI: 0.39–0.71; ≥70 years: HR=0.66, 95% CI: 0.39–1.13) and ORR (<70 years: 27.6% vs 15.4%; ≥70 years: 31.9% vs 17.6%) regardless of age. Younger patients on durvalumab received treatment longer (median total duration 45.5 vs 36.0 weeks). Regardless of treatment, older patients discontinued more due to AEs (durvalumab: 22.0% vs 13.7%; placebo: 16.1% vs 7.8%) and had more grade 5 AEs (durvalumab: 10.9% vs 2.7%; placebo: 9.1% vs. 4.5%). Among patients receiving durvalumab, older patients experienced more all-cause SAEs (42.6% vs 24.9%) and grade 3/4 AEs (41.6% vs 29.4%) but fewer AESIs (56.4% vs 67.9%) than younger patients.
8eea62084ca7e541d918e823422bd82e Conclusion
Patients achieved clinical benefit with durvalumab regardless of age. Increased AEs/SAEs observed in older patients across treatments may reflect age/cCRT related morbidity.
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