Skip to content
Bending the Curve Trial by Trial
?

ARCS-M

Anetumab ravtansine versus vinorelbine in patients with relapsed, mesothelin-positive malignant pleural mesothelioma (ARCS-M): a randomised, open-label phase 2 trial

Phase 2N = 248NCT02610140

Population
Adults (18 years or older) with unresectable locally advanced or metastatic malignant pleural mesothelioma overexpressing mesothelin, ECOG performance status 0-1, who had progressed on first-line platinum-pemetrexed chemotherapy with or without bevacizumab.
Design
Randomised (2:1), open-label phase 2 study at 76 hospitals in 14 countries: intravenous anetumab ravtansine 6.5 mg/kg on day 1 of each 21-day cycle or intravenous vinorelbine 30 mg/m2 weekly until progression, toxicity or death. Mesothelin overexpression (2+ or 3+ membrane staining on at least 30% of viable tumour cells) was screened prospectively; 589 patients were enrolled and 248 mesothelin-overexpressing patients were randomised between 3 December 2015 and 31 May 2017. Primary endpoint PFS by blinded central radiology review in the ITT population; overall survival was a secondary endpoint (final analysis cutoff 6 April 2018).
Primary endpoint
PFS
Arms
  • Anetumab ravtansine (experimental, n = 166): Anetumab ravtansine 6.5 mg/kg on day 1 of each 21-day cycle
  • Vinorelbine (control, n = 82): Vinorelbine 30 mg/m2 once every week
People
Kindler HL
PFSHR 1.22 (95% CI 0.85–1.74)Δ median PFS−0.2 monthsOSHR 1.07 (95% CI 0.76–1.51)Δ median OS−2.1 months
Show the numbers
Results reported for ARCS-M
EndpointAnalysisAnetumab ravtansineVinorelbineEffect
PFSProgression-free survival by blinded central radiology reviewprimaryKindler 2022median 4.3 months (4.1–5.2)median 4.5 months (4.1–5.8)HR 1.22 (95% CI 0.85–1.74)P=0.86The p value is the log-rank p. Progression or death in 105 (63%) of 166 patients with anetumab ravtansine and 43 (52%) of 82 with vinorelbine; median follow-up 4.0 months (IQR 1.4-5.5) and 3.9 months (1.4-5.4). Grade 3 or worse neutropenia in one (1%) of 163 versus 28 (39%) of 72 patients. The authors state that anetumab ravtansine was not superior to vinorelbine.
OSRandomised patients (248)finalKindler 2022median 9.5 months (8.3–12.3)median 11.6 months (8.6–13.1)HR 1.07 (95% CI 0.76–1.51)P=0.66Secondary endpoint, final efficacy analysis. The p value is the log-rank p. Deaths: 113 (68%) of 166 with anetumab ravtansine and 48 (59%) of 82 with vinorelbine; median follow-up 8.6 months (IQR 4.3-15.3) and 8.7 months (3.5-14.3). An exploratory OS analysis at the 2 July 2019 cutoff reported HR 0.98 (95% CI 0.72-1.34) with medians unchanged from the final analysis.
Results reported for ARCS-M
EndpointAnalysisAnetumab ravtansineVinorelbineEffect
PFSProgression-free survival by blinded central radiology reviewprimaryKindler 2022median 4.3 months (4.1–5.2)median 4.5 months (4.1–5.8)HR 1.22 (95% CI 0.85–1.74)P=0.86The p value is the log-rank p. Progression or death in 105 (63%) of 166 patients with anetumab ravtansine and 43 (52%) of 82 with vinorelbine; median follow-up 4.0 months (IQR 1.4-5.5) and 3.9 months (1.4-5.4). Grade 3 or worse neutropenia in one (1%) of 163 versus 28 (39%) of 72 patients. The authors state that anetumab ravtansine was not superior to vinorelbine.
OSRandomised patients (248)finalKindler 2022median 9.5 months (8.3–12.3)median 11.6 months (8.6–13.1)HR 1.07 (95% CI 0.76–1.51)P=0.66Secondary endpoint, final efficacy analysis. The p value is the log-rank p. Deaths: 113 (68%) of 166 with anetumab ravtansine and 48 (59%) of 82 with vinorelbine; median follow-up 8.6 months (IQR 4.3-15.3) and 8.7 months (3.5-14.3). An exploratory OS analysis at the 2 July 2019 cutoff reported HR 0.98 (95% CI 0.72-1.34) with medians unchanged from the final analysis.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS1.220.85–1.74
OS1.070.76–1.51
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%0246810Months (modelled)
  • Anetumab ravtansine (experimental)
  • Vinorelbine (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsAnetumab ravtansineVinorelbine
0100.0%100.0%
361.7%63.0%
638.0%39.7%
827.5%29.2%
1117.0%18.4%
Illustrative — modelled from reported values, not trial data. OS, final.
0%25%50%75%100%0510152025Months (modelled)
  • Anetumab ravtansine (experimental)
  • Vinorelbine (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsAnetumab ravtansineVinorelbine
0100.0%100.0%
760.0%65.8%
1533.5%40.8%
2220.1%26.9%
2912.1%17.7%
Primary publication: Kindler HL, Novello S, Bearz A, Ceresoli GL, Aerts JGJV, Spicer J, et al. Anetumab ravtansine versus vinorelbine in patients with relapsed, mesothelin-positive malignant pleural mesothelioma (ARCS-M): a randomised, open-label phase 2 trial. Lancet Oncol. 2022;23(4):540-552. PubMedDOI

Appears in

Sources

  1. Kindler HL, Novello S, Bearz A, Ceresoli GL, Aerts JGJV, Spicer J, et al. Anetumab ravtansine versus vinorelbine in patients with relapsed, mesothelin-positive malignant pleural mesothelioma (ARCS-M): a randomised, open-label phase 2 trial. Lancet Oncol. 2022;23(4):540-552.

    PubMedDOI