LBA TBC (ID 789)
LBA TBC (ID 790)
Invited Discussant TBC (ID 791)
Q&A (ID 792)
56O - A randomized, controlled, multicenter phase II trial of camrelizumab combined with albumin-bound paclitaxel and cisplatin as neoadjuvant treatment in resectable stage IIIA and IIIB(T3N2) non-small-cell lung cancer (ID 720)
- J. Lei (Xi’an City, China)
- J. Lei (Xi’an City, China)
- J. Zhao (Xian, China)
- X. Yan (Xi'an, China)
- L. Gong (Xian, China)
- G. Lei (Xi'an, China)
- T. Jiang (Xi'an, Shannxi, China)
Abstract
Background
Resectable NSCLC with neoadjuvant chemotherapy(CT) has favourable outcomes. However, with few neoadjuvant immunotherapy trials, detailed information on patients(pts) with resectable stage IIIA and IIIB(T3N2) NSCLC is available. Camrelizumab(Cam), a PD-1 antibody, has shown a survival benefit in patients with advanced NSCLC. However, the antitumor activity and safety of Cam plus CT in the neoadjuvant setting is unknown. Here, we report the final analysis from this multi-center, open-label, randomized controlled phase II trial.
Methods
Stage IIIA or IIIB(T3N2) resectable NSCLC were randomized (1:1) to receive Cam, albumin-bound paclitaxel (ab-Pac) and platinum, or ab-Pac plus platinum of a 21-day cycle for 3 cycles(n=47 each). Definitive surgery was to be performed within 4~6 weeks of treatment. The primary endpoint was pCR. Secondary endpoints included MPR, ORR, DFS by RECIST 1.1, and safety.
Results
From 3/2020 to 9/2022, 94 pts were enrolled and randomly assigned (n=47 each), and 88 pts received neoadjuvant treatment (43 in Cam+CT and 45 in CT). The patient characteristics of both arms were well balanced in the full analysis(FAS). In Cam+CT, 42 pts completed neoadjuvant therapy and efficacy evaluation, among of which 40 had underwent surgery, and in CT, 45 pts completed neoadjuvant therapy and efficacy evaluation, of which 42 underwent surgery. Neoadjuvant Cam+CT significantly increased the pCR rate compared to chemo in the FAS (32.56% vs 8.89%, P =0.0079). Cam+CT also improved MPR rates vs chemo in the FAS (15.56% vs 65.12%), as well as ORR (53.33% vs 72.09%), and 1-year DFS achieved 93.243% and 81.377% respectively. Adverse events (AEs) of the two arms were similar, except reactive cutaneous capillary endothelial proliferation (44.19%; grade 1-2) in the Cam+CT arm. No AEs beyond expectation or of grade 3-5 were reported.
Conclusions
This updated analysis confirms the superiority of the chemo-immuno combination in patients with resectable stage IIIA or IIIB(T3N2) NSCLC in terms of pCR, with a moderate increase in grade 3-5 toxicity. Thus, this treatment should become the standard of care in these patients.
Clinical trial identification
NCT04338620
1O - IMpower010: ctDNA status in patients (pts) with resected NSCLC who received adjuvant chemotherapy (chemo) followed by atezolizumab (atezo) or best supportive care (BSC) (ID 615)
- E. Felip (Barcelona, Spain)
- E. Felip (Barcelona, Spain)
- M. Srivastava (South San Francisco, United States of America)
- M. Reck (Grosshansdorf, Germany)
- H. Wakelee (Stanford, CA, United States of America)
- N. Altorki (New York, United States of America)
- E. Vallieres (Seattle, WA, United States of America)
- R. Liersch (Muenster, Germany)
- M. Harada (Sapporo, Japan)
- H. Tanaka (Niigata, Japan)
- J. Hamm (Louisville, United States of America)
- S. McCune (Marietta, United States of America)
- E. Bennett (South San Francisco, United States of America)
- B. Gitlitz (South San Francisco, United States of America)
- V. McNally (Welwyn Garden City, Herts, United Kingdom)
- S. Novello (Orbassano, Italy)
- M. Ballinger (South San Francisco, United States of America)
- W. Zou (South San Francisco, United States of America)
- B. Nabet (South San Francisco, United States of America)
- M. Das Thakur (South San Francisco, United States of America)
- C. Zhou (Shanghai, China)
Abstract
Background
IMpower010 (NCT02486718) showed that adjuvant atezo improved disease-free survival (DFS) vs BSC in pts with PD-L1 tumour cell (TC) ≥1% stage II-IIIA NSCLC. While a ctDNA positive (+) status post-surgery (Post-OP ctDNA) conferred poor prognosis, atezo was beneficial vs BSC irrespective of Post-OP ctDNA status (Zhou ESMO-IO 2021). The current exploratory analysis evaluated (1) association of atezo clinical outcomes by PD-L1 status and Post-OP ctDNA status and (2) association of ctDNA clearance post-chemo and pre-atezo cycle 1 day 1 (Post-chemo ctDNA), as well as post-atezo/BSC treatment (on-treatment), with DFS by arm in atezo and BSC pts.
Methods
Of 1005 randomized pts, 600 were evaluated for Post-OP ctDNA using the Signatera (Natera) RUO test. 118 of 600 pts were Post-OP ctDNA+. Of these, 103 pts were evaluated for ctDNA Post-chemo ctDNA and on-treatment at Wk 6 (C3; n=94), Wk 12 (C5; n=85), Wk 18 or 21 (C7/8; n=73) and Wk 42 or 45 (C15/16; n=46). PD-L1 TC subgroups <1%, ≥1%, 1-49% and ≥50% were determined using the VENTANA SP263 assay.
Results
Regardless of Post-OP ctDNA status, atezo was associated with improved DFS vs BSC in PD-L1+ subgroups (TC ≥1%, 1-49%, ≥50%) but not the PD-L1− subgroup (TC <1%). 62.1% (64/103) of Post-OP ctDNA+ pts were cleared (ctDNA−) at Post-chemo ctDNA, which was linked to improved DFS. Atezo improved DFS vs BSC regardless of ctDNA clearance at Post-chemo ctDNA (Cleared: DFS, 31.3 (atezo) vs 13.3 mo (BSC); HR [95% CI], 0.7 [0.37, 1.34] vs Not cleared: DFS, 4.2 vs 3.9 mo; 0.67 [0.34, 1.32]). Longitudinal assessment of ctDNA+ pts at Post-chemo ctDNA showed that atezo maintained ctDNA levels over time, while an approximate 10× increase was observed with BSC. The median time to convert to ctDNA+ in pts who were ctDNA− at Post-chemo ctDNA was longer with atezo vs BSC (not reached vs 4.67 mo; HR, 0.60 [95% CI: 0.31, 1.17]). Similarly, improved DFS was seen with atezo vs BSC in these pts (31.3 vs 13.3 mo; HR, 0.7 [95% CI: 0.37, 1.34]).
Conclusions
Adjuvant atezo is linked to improved DFS vs BSC in early NSCLC in PD-L1+ subgroups regardless of ctDNA status. Chemo ctDNA clearance is associated with longer DFS and atezo may control ctDNA levels and delay disease recurrence better than BSC.
Clinical trial identification
NCT02486718
Editorial acknowledgement
Medical writing support for this abstract was provided by Michael Williams, PhD, of Health Interactions, Inc. and funded by F. Hoffmann-La Roche, Ltd.