Management of Adverse Events and treatment interruption
toxicity
ADVERSE EVENTS
Guidelines for the management of AEs are provided in the supplementary appendix [see Additional file Tiragolumab and atezolizumab may be held for a maximum of 12 weeks (or approximately four cycles).If tiragolumab is interrupted for more than approximately 12 weeks for any reason, the patient will have to permanently discontinue tiragolumab treatment but may continue atezolizumab if there is no contraindication and after discussion with the coordinating investigator to determine whether the toxicity is considered related to tiragolumab and/or to the combination. Continued dosing with single-agent atezolizumab administered to patients will require that all other study eligibility criteria continue to be met. An exception can be made if, in the judgment of the investigator, the patient is likely to derive clinical benefit from resuming tiragolumab after a hold longer than 12 weeks. In this case, tiragolumab may be restarted with the approval of the coordinator of the study by contacting the sponsor for advice.If atezolizumab is interrupted for more than approximately 12 weeks (or approximately four cycles), the patient will have to permanently discontinue atezolizumab. However, if, in the judgment of the investigator, the patient is likely to derive clinical benefit from atezolizumab after a hold longer than 12 weeks, atezolizumab may be restarted with the approval of the coordinator of the study by contacting the sponsor for advice.If a patient must be tapered off steroids used to treat adverse events, atezolizumab may be withheld for an additional time beyond approximately 12 weeks from the last dose, and tiragolumab may be withheld for an additional time beyond approximately 12 weeks from the last dose until steroids are discontinued or until steroids are reduced to a prednisone dose (or dose equivalent) ≤ 10 mg/day. The acceptable length of interruption will depend on an agreement between the investigator and the coordinator of the study after contacting the sponsor for advice and approval. Dose interruptions for reason(s) other than toxicity, such as surgical procedures, may be allowed with the coordinator of the study by contacting the sponsor for advice and approval.After both tiragolumab and atezolizumab have been permanently discontinued, the patient will be monitored for safety and efficacy.