Table 2. Characteristics of the included studies in immunotherapy-related HPD.
| Authors | Publication year |
Study design | Tumor type | Treatment | Incidence of HPD | Definition of HPD | Predictive factor of HPD | Survival outcome for the HPD |
|---|---|---|---|---|---|---|---|---|
| Lahmar et al. (6) | 2016 | Retrospective | NSCLC | Nivolumab, pembrolizumab, atezolizumab | 10.1% (9/89) | TGR >50% | – | – |
| Champiat et al. (4) | 2017 | Retrospective | Melanoma, lung cancer, renal cancer, colorectal cancer, urothelial cancer, and others | Anti-PD-1/PD-L1 monotherapy | 9.2% (12/131) | RECIST progression disease at first evaluation | Age | HPD patients: median OS 4.6 months (95% CI, 2.0–NA) |
| TGRR ≥2 | Non-HPD patients: median OS 7.6 months (95% CI, 5.9–16.0) | |||||||
| Saâda-Bouzid et al. (19) | 2017 | Retrospective | Head and neck squamous cell carcinoma (HNSCC) | Anti-PD-1/PD-L1 mAbs | 29.4% (10/34) | TGKR ≥2 | Metastatic cervical nodes | HPD patients: PFS according to RECIST and irRECIST: 2.5, 2.9 months (P=0.003); OS 6.1 months (P=0.77) |
| The presence of a regional recurrence | Non-HPD patients: PFS according to RECIST and irRECIST: 3.4, 5.1 months (P=0.003); OS 8.1 months (P=0.77) | |||||||
| Kato et al. (30) | 2017 | Genomic analysis | Bladder cancer, squamous cell carcinoma, breast cancer, endometrial stromal, sarcoma, lung cancer | CTLA-4, PD-1/PD-L1 inhibitors, or other agents | 3.9% (6/155) | TTF <2 months | MDM2/4 family amplification | – |
| Tumor burden increased by 50% | Epidermal growth factor receptor mutations | |||||||
| Progression rate increase >2-fold | ||||||||
| Ferrara et al. (20) | 2018 | Retrospective | NSCLC | Anti-PD-1/PD-L1 mAbs vs. single-agent chemotherapy | Immunotherapy cohort:13.8% (56/406) | ΔTGR exceeding 50% | More than 2 metastatic sites before PD-1/PD-L1 |
HPD patients: median OS 3.4 months (95% CI, 2.8–7.5 months) |
| Non-HPD patients: median OS 6.2 months (95% CI, 5.3–7.9 months) | ||||||||
| Kanjanapan et al. (18) | 2019 | Retrospective | Head and neck, gynecological, lung, gastrointestinal, genitourinary, melanoma, endocrine, breast cancer, and sarcoma | PD-1/PD-L1 inhibitors or other checkpoint inhibitors | – | RECIST1.1 progression at the first on treatment | Age | HPD patients: PFS 1.6 months (HR: 3.7; 95% CI, 2.0–7.1; P<0.001); OS 5.9 months (HR: 1.7; 95% CI, 0.9–3.3; P=0.11) |
| ≥2-fold increase in TGR | Sex | Non-HPD patients: PFS 2.8 months (HR: 3.7; 95% CI, 2.0–7.1; P<0.001); OS 14.3 months (HR: 1.7; 95% CI, 0.9–3.3; P=0.11) | ||||||
| Immunotherapy toxicity | ||||||||
| Lo Russo et al. (23) | 2019 | Prospective | NSCLC | Anti-PD-1/PD-L1 mAbs | 25.7% (39/152) | TTF <2 months | NA | HPD patients: median OS 4.4 months (95% CI, 3.4–5.4) |
| The total major diameter of the target lesion increased by ≥50% | Non-HPD patients: median OS 17.7 months (95% CI, 13.4–24.1) | |||||||
| At least 2 new lesions in an already involved organ | ||||||||
| Appearance of new involved organ | ||||||||
| Decrease of ECOG scores ≥2 during the first 2 months of treatment | ||||||||
| Gandara et al. (45) | 2018 | Prospective | NSCLC | Atezolizumab vs. docetaxel | Atezolizumab: 10.4% (44/425) | Sum of longest diameters (per investigator) increased by 50% from baseline to first assessment or death due to PD | NA | – |
| Kim et al. (28) | 2019 | Retrospective | NSCLC | Ant-PD-1/PD-L1 mAbs | 20.5% (54/263) | RECIST 1.1 progression at the first response evaluation | >2 metastatic sites | HPD patients: PFS 19 days (HR: 4.619; 95% CI, 2.868–7.440); median OS 50 days (HR: 5.079; 95% CI, 3.136–8.226) |
| Two-fold increase of TGK or TGR between the experimental period and reference period | Liver metastases | Non-HPD patients: PFS 48 days (HR: 4.619; 95% CI, 2.868–7.440); median OS 205 days (HR: 5.079; 95% CI, 3.136–8.226) | ||||||
| TTF <2 months | Higher serum lactate dehydrogenases level | |||||||
| RMH score >2 | ||||||||
| Sasaki et al. (35) | 2019 | Retrospective | NSCLC | Anti-PD-1/PD-L1 mAbs | 21.0% (13/62) | TGKR ≥2 and >50% increase in tumor burden | Advanced gastric cancer patients with poor performance status | HPD patients: median PFS 0.7 months (P<0.001); median OS 2.3months (P<0.001) |
| Liver metastases | Non-HPD patients: median PFS 2.4 months (P<0.001); median OS not reach (P<0.001) | |||||||
| Large tumor size | ||||||||
| Higher neutrophil-to-lymphocyte ratio | ||||||||
| Higher C-reactive protein level | ||||||||
| Higher serum LDH | ||||||||
| Tunali et al. (46) | 2019 | Retrospective | Gastric cancer | CTLA-4, PD-1/PD-L1 inhibitors or other agents | 21.0% (13/62) | RECIST-defined PD at first evaluation and TGRR ≥2, and TTF <2 months | RMH prognostic score ≥2 | – |
| Higher serum LDH | ||||||||
| Ji et al. (47) | 2019 | Retrospective | Stomach, esophagus, colorectal, liver, pancreas, and ampulla cancer | PD-1/PD-L1 inhibitor alone or combined with the CTLA-4 inhibitor | 20.0% (5/25) | The TGKR ≥2 | Age | – |
| Neuroendocrine cancer | ||||||||
| Refae et al. (31) | 2020 | Retrospective | NSCLC, HNSCC, melanoma, renal cell carcinoma (RCC) | Anti-PD-1/PD-L1 monotherapy | 11 (14%) | TGKR ≥2 | Age ≥70 years | Median follow-up was 13.3 months (95% CI, 10.6–15.4); median irPFS 16.8 months (95% CI, 10.2–NA); median OS: not reached |
| Immune-relate toxicity grade ≥3 | ||||||||
| VEGFR 2 rs1870377A/T or A/A | ||||||||
| PD-L1 rs2282055 G/T or G/G | ||||||||
| PD-L1 rs2227981 G/G | ||||||||
| Matos et al. (48) | 2020 | Retrospective | Melanoma, NSCLC, xcolorectal cancer, triple-negative breast cancer, head and neck cancer, cervical cancer, bladder, others | Anti-PD-1/PD-L1 mAbs | RECIST cohort: 10.7% (29/270); TGR cohort: 6.3% (14/221) | RECIST cohort: RECIST-defined PD in the 8 weeks after treatment initiation; HPD =1.2× baseline sum target lesions + new lesions in at least 2 different organs | NA | HPD patients: median OS according to TGR criteria: 4.2 months (95% CI, 2.07–6.33); median OS according to RECIST: 5.23 months (95% CI, 3.97–6.45) |
| TGR cohort: TGRR ≥2 | Non-HPD patients: median OS according to TGR criteria: 6.27 months (95% CI, 3.88–8.67); median OS 7.33 months (95% CI, 4.53–10.12) |
TGK, tumor growth kinetics [the change in the sum of the longest diameters (SLD) of the target lesions according to RECIST1.1 criteria per month]; TGR, tumor growth rate (the difference between TGR during ICIs and TGR at baseline); TGKR, TGK post-immunotherapy/TGK pre-immunotherapy; TGRR, TGR post-immunotherapy/TGR pre-immunotherapy; TTF, time to treatment failure (the time from the initiation of ICIs to the discontinuation of ICIs for any reason, including progression, patient preference, toxicity, or death); ECOG, Eastern Cooperative Oncology Group; RMH prognostic score, Royal Marsden Hospital prognostic score; RECIST, Response Evaluation Criteria in Solid Tumors; irRECIST, immune-related RECIST; irPFS, immune-related PFS; HPD, hyperprogressive disease; NSCLC, non-small cell lung cancer; VEGFR, vascular endothelial growth factor receptor; OS, overall survival; PFS, progression-free survival; HR, hazard ratio; CI, confidence interval; mAbs, monoclonal antibodies; ICI, immune checkpoint inhibitor; NA, not available.