Table 2. .
Trials using immunotherapeutic agents and immune-related response assessment criteria
| Author; journal and year | No. of patients/tumours and study design/disease group | Trial agent | Response criteria | Observations |
| Kim, Cancer Chemother Pharmacol, 201716 | 41 patients; retrospective; Non-small cell lung cancer | Immune checkpoint inhibitors | RECIST 1.1 and irRC | ORR was 29.2% [95% CI (17.6–44.5)] as assessed by RECIST and 34.1% [95% CI (21.6–49.4)] by irRC. Pseudo-progression was observed in RECIST 1.1 but not in irRC, which showed a durable response to immunotherapy. These atypical responses could be missed as PD by RECIST |
| Khoja L, Br J Cancer, 201617 | 37 patients; retrospective; metastatic melanoma | Pembrolizumab | RECIST 1.1, irRC | Delayed response post first scan was seen in 5% of RECIST PD cases and 14% of irRC PD cases. 5% (2 out of 37) of treated patients, who were initially characterized as PD by RECIST criteria, did go on to demonstrate some treatment benefit. |
| Rosenberg JE, Lancet. 201618 | 315 patients; multicentre phase II trial; urothelial cancer | Atezolizumab | RECIST 1.1 and irRECIST | Compared with a historical control overall response rate of 10%, treatment with atezolizumab resulted in a significantly improved RECIST v. 1.1 objective response rate for each pre-specified immune cell group {IC2/3: 27% [95% CI (19–37)], p < 0·0001; IC1/2/3: 18% (13–24), p = 0·0004} and in all patients [15% (11–20), p = 0·0058] |
| Wilgenhof S, J Clin Oncol. 201619 | 39 patients, phase II trial; melanoma | Autologous monocyte-derived mRNA electroporated dendritic cells (TriMixDC-MEL) plus ipilimumab | irRC criteria | Six-month disease control rate according to the immune-related response criteria served as the primary end point. The 6-month disease control rate was 51% [95% CI (36–67%)], and the overall tumour response rate was 38% (including eight complete and seven partial responses) |
| McDermott DF, J Clin Oncol. 201620 | 70 patients, phase IA; renal cell cancer | Atezolizumab | RECIST 1.1 and irRC | Secondary end points assessed clinical activity per Response Evaluation Criteria in Solid Tumours v. 1.1 and immune-related response criteria |
| Hodi FS, J Clin Oncol. 201621 | 655 patients phase Ib; melanoma | Pembrolizumab | RECIST 1.1 and irRC criteria | Modified criteria that permit treatment beyond initial progression per RECIST v. 1.1 might prevent premature cessation of treatment, as conventional RECIST might underestimate the benefit of pembrolizumab in approximately 15% of patients |
| Chiarion Sileni V, J Exp Clin Cancer Res. 201422 | 188 patients retrospective; melanoma | Ipilimumab | irRC criteria | The immune-related disease control rate among 188 evaluable patients was 38%, including 4 for irCR, 24 with irPR and 44 with irSD |
| Bapsy PP, Cytotherapy. 201423 | 51 patients, multicentre, phase II; solid tumours | Autologous dendritic cell (DC) formulation | RECIST 1.1 and irRC criteria | Objective response rate by Response Evaluation Criteria In Solid Tumours was 28.9% (11/38) and immune-related response criteria was 42.1% (16/38); 90% confidence interval for objective response rate was (17.2, 43.3) and (28.5, 56.7) by Response Evaluation Criteria In Solid Tumours and immune-related response criteria, respectively |
| Wolchok JD, N Engl J Med. 201324 | 53 patients, phase I trial; melanoma | Nivolumab plus ipilimumab | irRC | Evidence of clinical activity (conventional, unconfirmed, or immune-related response or stable disease for ≥ 24 weeks) was observed in 65% of patients |
| Di Giacomo AM, Lancet Oncol. 201225 | 86 patients; open label, phase II trial; melanoma | Ipilimumab and fotemustine | irRC criteria | The primary endpoint was the proportion of patients with immune-related disease control as established with immune-related response criteria. 40 patients in the study population achieved disease control [46·5%, 95% CI (35·7–57·6)], as did 10 with brain metastases (50·0%, 27·2–72·8) |
| Lynch TJ, J Clin Oncol. 201226 | 204 patients, multicentre, phase II trial; non-small cell lung cancer | Ipilimumab with paclitaxel and carboplatin | irRC and modified WHO criteria | The study met its primary end point of improved irPFS for phased ipilimumab vs the control [hazard ratio (HR), 0.72; p = .05], but not for concurrent ipilimumab (HR, 0.81; p = 0.13). Phased ipilimumab also improved PFS according to modified WHO criteria (HR, 0.69; p = 0.02). Phased ipilimumab plus paclitaxel and carboplatin improved irPFS and PFS, which supports additional investigation of ipilimumab in NSCLC |
| Hamid O, J Transl Med. 201127 | 82 patients, phase II trial; melanoma | Ipilimumab | Modified WHO criteria | Baseline expression of immune-related tumour biomarkers and a post-treatment increase in tumour-infiltrating lymphocytes may be positively associated with ipilimumab clinical activity |
| O'Day SJ Ann Oncol. 201028 | 155 patients, multicentre, phase II trial; melanoma | Ipilimumab | irRC and modified WHO criteria | In patients with pre-treated advanced melanoma with primary endpoint of best overall response rate (BORR), irRC criteria showed a disease control rate of 35% as compared to 27% by WHO |
BORR, best overall response rate; CI, confidence interval; DC, dendritic cell; irPFS,immune-related PFS; irPR, immune-related Partial Response; irRC, immune-related response criteria; irRECIST, immune-related RECIST; irSD, immune-related Stable Disease; NSCLC, non-small cell lung cancer; ORR, overall response rate; PD, progressivedisease; PFS, progression free survival; RECIST, Response Evaluation CriteriaIn Solid Tumours; WHO, World Health Organization.