Opdivo ( Nivolumab ) was approved by the U.S. Food and Drug Administration ( FDA ) for the treatment of patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma ( ESCC ) after prior fluoropyrimidine- and Platinum-based chemotherapy.
This application was granted Priority Review Designation by the FDA, and the approval is based on the phase 3 ATTRACTION-3 trial in which Nivolumab ( n=210 ) has demonstrated superior overall survival ( OS ) versus taxane chemotherapy ( n=209 ) ( investigator’s choice of Docetaxel or Paclitaxel ) ( hazard ratio, HR=0.77; 95% confidence interval [ CI ]: 0.62 to 0.96; p=0.0189 ).
The median OS was 10.9 months ( 95% CI: 9.2 to 13.3 ) for Nivolumab compared to 8.4 months ( 95% CI: 7.2 to 9.9 ) for Docetaxel or Paclitaxel.
Opdivo is the first approved immunotherapy in this setting regardless of tumor PD-L1 expression level.
ATTRACTION-3 is a phase 3, multicenter, randomized, active-controlled, open-label global study evaluating Nivolumab versus taxane chemotherapy ( investigator’s choice of Docetaxel or Paclitaxel ) in patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma, refractory or intolerant to at least one prior fluoropyrimidine- and Platinum-based regimen.
The trial included patients regardless of tumor PD-L1 status, but tumor specimens were evaluated prospectively using the PD-L1 IHC 28-8 pharmDx assay at a central laboratory.
Patients were randomized to receive Nivolumab 240 mg by intravenous infusion over 30 minutes every 2 weeks ( n=210 ) or investigator’s choice of taxane chemotherapy ( n=209 ) of either Docetaxel 75 mg/m2 intravenously every 3 weeks ( n=65 ), or Paclitaxel 100 mg/m2 intravenously once a week for 6 weeks followed by 1 week off ( n=144 ).
Patients were treated until disease progression, assessed by the investigator per RECIST v1.1, or unacceptable toxicity.
The major efficacy outcome measure was overall survival. Additional efficacy outcome measures included overall response rate ( ORR ) and progression-free survival ( PFS ) as assessed by the investigator using RECIST v1.1 and duration of response ( DOR ).
There was no statistically significant difference between the two arms for ORR ( 19.3% [ 33/171, 95% CI: 13.7 to 26.0 ] versus 21.5% [ 34/158, 95% CI: 15.4 to 28.8 ] for Nivolumab ( 0.6% complete response [ CR ] and 18.7% partial response [ PR ] ) and investigator’s choice chemotherapy ( 1.3% CR and 20.3% PR ), respectively; p=0.6323 ).
The median PFS was 1.7 months ( 95% CI: 1.5 to 2.7 ) for Opdivo versus 3.4 months ( 95% CI: 3.0 to 4.2 ) for investigator’s choice chemotherapy ( HR=1.1; 95% CI: 0.9 to 1.3 ), however it was not tested due to the pre-specified hierarchical testing strategy.
The safety of Nivolumab was evaluated in ATTRACTION-3 in 209 patients. Serious adverse reactions occurred in 38% of patients receiving Nivolumab. Serious adverse reactions reported in 2% or more of patients who received Nivolumab were pneumonia, esophageal fistula, interstitial lung disease and pyrexia.
Nivolumab was discontinued in 13% of patients and was delayed in 27% of patients for an adverse reaction.
The most common adverse reactions occurring in greater than or equal to 20% of Nivolumab-treated patients were rash ( 22% ) and decreased appetite ( 21% ).
In the United States, it is estimated that approximately 18,440 new cases of esophageal cancer will be diagnosed and approximately 16,170 deaths will result from the disease this year alone. ( Xagena )
Source: BMS, 2020