H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL
Scott Joseph Antonia , Julie R. Brahmer , Scott N. Gettinger , Laura Quan Man Chow , Rosalyn A. Juergens , Frances A. Shepherd , Scott Andrew Laurie , David E. Gerber , Jonathan Wade Goldman , Yun Shen , Christopher Harbison , Suresh Alaparthy , Allen C. Chen , Hossein Borghaei , Naiyer A. Rizvi
Background: First-line PT-DC has demonstrated 1-yr overall survival (OS) rates of up to 54% in NSCLC; however, there remains a need for therapies with improved long-term survival. We report an updated analysis of a phase I multi-cohort study evaluating nivolumab, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, plus PT-DC in chemotherapy-naive patients (pts) with advanced NSCLC, with longer follow up and additional pts. Methods: Pts (N=56) with advanced NSCLC were assigned based on histology to 4 cohorts to receive nivolumab 10 mg/kg IV Q3W plus concurrent IV gemcitabine 1250 mg/m2 + cisplatin 75 mg/m2 (squamous [sq]) or pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 (non-sq), or nivolumab 5 or 10 mg/kg IV Q3W plus IV paclitaxel 200 mg/m2+ carboplatin AUC6 (sq + non-sq), in a phase I dose de-escalation trial to assess dose-limiting toxicity (DLT). PT-DC was given for 4 cycles, followed by nivolumab until progression or unacceptable toxicity. Objective response rate (ORR) was assessed by RECIST 1.1. Results: No DLTs were seen during the first 6 wks of treatment. Grade 3-4 treatment-related adverse events were reported in 45% of pts (25-73% across arms), including pneumonitis (4 pts, 7%; managed by protocol algorithm), and fatigue and acute renal failure (3 pts [5%] each). Across arms, ORR (≥10 months follow up) was 33–50% and progressive disease (PD) as best overall response (BOR) was infrequent (Table). One-year OS rates were 59–87% (Table). Conclusions: Nivolumab combined with standard PT-DC regimens used for first-line treatment of NSCLC demonstrated antitumor activity, with encouraging 1-yr OS and an acceptable tolerability profile. Clinical trial information: NCT01454102.
Nivo 10 + gem/cis Sq |
Nivo 10 + pem/cis Non-sq |
Nivo 10 + pac/carb Sq + Non-sq |
Nivo 5 + pac/carb Sq + Non-sq |
|
---|---|---|---|---|
N | 12 | 15 | 15 | 14 |
ORR, a n (%) | 4 (33) | 7 (47) | 7 (47) | 7 (50) |
Median duration of response (Kaplan-Meier),a wk (range) |
20.9 (12.1–41.7+) |
32.0 (13.1–42.1+) |
25.6 (11.4+–39.0+) |
Not reached (11.4–37.3+) |
PD as BOR, n (%) | 0 | 0 | 3 (20) | 1 (7) |
PFS rate wk 24, % | 36 | 71 | 38 | 57 |
1-yr OS, % | 59 | 87 | 59 | Insufficient follow-up |
a Confirmed responses only. + Ongoing.
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Abstract Disclosures
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