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Browsing Over 135 Presentations
98O - First-line nivolumab (NIVO) + ipilimumab (IPI) + 2 cycles chemotherapy (chemo) vs 4 cycles chemo in advanced non-small cell lung cancer (aNSCLC): association of blood and tissue tumor mutational burden (TMB) with efficacy in CheckMate 9LA
- L. Paz-Ares (Madrid, Spain)
- L. Paz-Ares (Madrid, Spain)
- T. Ciuleanu (Cluj-Napoca, Romania)
- M. Cobo (Malaga, Spain)
- M. Schenker (Craiova, Romania)
- B. Zurawski (Bydgoszcz, Poland)
- J. Menezes (Porto Alegre, Brazil)
- E. Richardet (Córdoba, Argentina)
- J. Bennouna (Nantes, France)
- E. Felip (Barcelona, Spain)
- O. Juan-Vidal (Valencia, Spain)
- A. Alexandru (Bucharest, Romania)
- H. Sakai (Saitama, Japan)
- A. Scherpereel (Lille, France)
- M. Reck (Grosshansdorf, Germany)
- S. Lu (Shanghai, China)
- T. John (Heidelberg, VIC, Australia)
- S. Meadows-Shropshire (Princeton, NJ, United States of America)
- D. Balli (Princeton, NJ, United States of America)
- S. Agrawal (Princeton, NJ, United States of America)
- D. Carbone (Columbus, OH, United States of America)
Abstract
Background
In CheckMate 9LA (NCT03215706), 1L NIVO + IPI + chemo (2 cycles) significantly improved overall survival (OS) vs chemo (4 cycles) in patients (pts) with aNSCLC regardless of tumor histology or PD-L1 expression. TMB is potentially associated with the clinical efficacy of immune checkpoint inhibitors. We evaluated efficacy by tissue and blood TMB (tTMB/bTMB) in CheckMate 9LA.
Methods
tTMB was evaluated using the FoundationOne CDxTM assay from tissue samples collected prior to enrollment. Plasma samples collected at baseline were used for isolation of circulating cell-free tumor DNA and evaluation of bTMB using the Guardant OMNI platform. TMB was not a stratification factor for randomization. Analyses of OS, progression-free survival (PFS), and objective response rate (ORR) were based on prespecified TMB thresholds (tTMB, 10 mut/Mb; bTMB, 16 and 20 mut/Mb). Analyses were based on the March 9, 2020 database lock (DBL; minimum OS follow-up, 12.7 mo).
Results
Of 711 randomized pts with available TMB data at DBL, 64% had evaluable tTMB and 73% had evaluable bTMB. Baseline characteristics were generally well balanced between all randomized, TMB-evaluable and non-evaluable, as well as TMB-high and TMB-low subgroups (both bTMB and tTMB). Overall, clinical benefit (OS, PFS, ORR) was observed with NIVO + IPI + chemo vs chemo in both TMB-high and TMB-low subgroups (Table). The OS benefit with NIVO + IPI + chemo vs chemo was similar between tTMB ≥ 10 and < 10 mut/Mb, and between bTMB ≥ 16 and < 16 mut/Mb subgroups; a numerically higher OS benefit was seen in bTMB ≥ 20 vs < 20 mut/Mb subgroups. For PFS and ORR, the magnitude of benefit was higher in TMB-high versus TMB-low subgroups for both tTMB and bTMB.
| Table. Efficacy outcomes in subgroups based on blood and tissue TMB | ||||||||||||
| TMB cut-off (mut/Mb) | ||||||||||||
| tTMB ≥10 | tTMB <10 | bTMB ≥16 | bTMB <16 | bTMB ≥20 | bTMB <20 | |||||||
| N + I + chemo n = 101 | Chemo n = 82 | N + I + chemo n = 135 | Chemo n = 138 | N + I + chemo n = 113 | Chemo n = 85 | N + I + chemo n = 165 | Chemo n = 156 | N + I + chemo n = 80 | Chemo n = 61 | N + I + chemo n = 196 | Chemo n = 180 | |
| Median OS, mo | 15.0 | 10.8 | 16.8 | 12.4 | 15.4 | 10.4 | 15.0 | 11.2 | 19.4 | 11.4 | 14.1 | 10.8 |
| HR (95% CI) | 0.74 (0.51−1.08) | 0.75 (0.55−1.02) | 0.60 (0.42−0.86) | 0.73 (0.55−0.96) | 0.54 (0.35−0.84) | 0.74 (0.57−0.95) | ||||||
| Median PFS, mo | 8.9 | 4.7 | 5.6 | 5.0 | 7.2 | 5.3 | 5.6 | 4.5 | 9.7 | 5.3 | 5.6 | 4.5 |
| HR (95% CI) | 0.49 (0.34−0.70) | 0.83 (0.63−1.10) | 0.55 (0.39−0.78) | 0.78 (0.60− 1.00) | 0.48 (0.32−0.73) | 0.78 (0.62−0.99) | ||||||
| ORR, % | 46 | 28 | 33 | 27 | 49 | 27 | 33 | 28 | 55 | 31 | 33 | 27 |
Conclusions
Higher TMB appeared to be associated with improved PFS and ORR benefits of NIVO + IPI + chemo over chemo. OS benefit was generally similar between high and low TMB.
Clinical trial identification
NCT03215706
Editorial acknowledgement
Writing and editorial assistance were provided by Nick Patterson, of Caudex, London, UK, funded by Bristol Myers Squibb.
TBC
When should I initiate, stop and resume systemic treatment?
- B. Besse (Villejuif, CEDEX, France)
Q&A and live discussion
79MO - PACIFIC-R: real-world characteristics of unresectable Stage III NSCLC patients treated with durvalumab after chemoradiotherapy
- F. McDonald (London, United Kingdom)
- F. McDonald (London, United Kingdom)
- F. Mornex (Lyon, France)
- M. Garassino (Milan, Italy)
- A. Filippi (Pavia PV, Italy)
- D. Christoph (Essen, Germany)
- V. Haakensen (Oslo, Norway)
- A. Agbarya (Haifa, Israel)
- M. Van den Heuvel (Amsterdam, Netherlands)
- P. Vercauter (Aalst, Belgium)
- C. Chouaid (Créteil, France)
- E. Pichon (Tours, France)
- S. Siva (Melbourne, VIC, Australia)
- L. Steinbusch (Amsterdam, Netherlands)
- I. Peretz (Tel Aviv, Israel)
- B. Solomon (Melbourne, VIC, Australia)
- L. Decoster (Jette, Belgium)
- W. Sawyer (Cambridge, United Kingdom)
- A. Allen (Gaithersburg, MD, United States of America)
- M. Licour (Paris, France)
- N. Girard (Paris, France)
Abstract
Background
The PACIFIC regimen (up to 12 months of durvalumab treatment in pts with unresectable Stage III non-small-cell lung cancer [NSCLC] who did not progress after platinum-based concurrent chemoradiotherapy [cCRT]) is now standard of care. Insights into durvalumab use outside the clinical trial setting are needed.
Methods
PACIFIC-R (NCT03798535) is a large international, observational study of pts with unresectable Stage III NSCLC who received ≥1 dose of durvalumab (10 mg/kg Q2W) as part of an AstraZeneca-initiated expanded access programme (September 2017–December 2018). Pts must have completed platinum-based chemotherapy (CT) concurrent or sequential to radiotherapy (RT) within the previous 12 weeks without evidence of disease progression. Data will be retrospectively collected up to 5 years after enrolment.
Results
The full analysis set (N=1155) showed no significant differences in baseline demographics and disease characteristics by PD-L1 expression status (tested pts: ≥1% [n=574] vs <1% [n=138]). A majority of pts had received cCRT (n=893). Pts who had received sequential CRT (sCRT; n=164) were generally older (37.8% vs 28.4% aged ≥70 years); a higher proportion had larger tumour volume (25.0% vs 15.9% >70 mm). Median total RT dose (overall: 65 Gy) and duration (overall: 1.5 months) reflected local practice. For platinum-based CT regimens, vinorelbine was favoured in France/Germany/UK; paclitaxel in Australia/Israel; and etoposide in Netherlands/Belgium/Norway. Median CT duration ranged from 0.8 to 2.3 months (overall: 1.6 months). Median time of durvalumab start from end of CRT varied from 39 to 89 days (overall: 52 days). Most commonly reported adverse events of special interest (AESIs) in the first 3 months of durvalumab treatment were pneumonitis (10.6%) and endocrinopathies (6.8%), leading to permanent treatment discontinuation in 4.8% and 0.2% of pts, respectively.
Conclusions
Real-world characteristics of PACIFIC-R pts reflect the PACIFIC population (only cCRT was allowed per protocol in PACIFIC). Time to durvalumab start from end of CRT was longer than in PACIFIC (except France: durvalumab start ≤6 weeks from end of CRT per protocol). Permanent discontinuation due to AESIs was infrequent.
Clinical trial identification
PACIFIC-R (NCT03798535) - release date not applicable
Editorial acknowledgement
Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Carole Mongin-Bulewski of Cirrus Communications (Macclesfield, UK), an Ashfield company, and was funded by AstraZeneca.
Invited Discussant 100MO and 101MO
IO in stage III
- J. Lee (Los Angeles, United States of America)
Presentation of case
- M. White (Stanford, United States of America)
Define biomarker in SCLC
- M. Frühh (St. Gallen, Switzerland)
Invited Discussant 96O, 97O and 98O
Q&A and live discussion
Biological rationale for I-O combinations in solid tumours
- N. Rizvi (New York, NY, United States of America)