Hyperprogression and impact of tumor growth kinetics after PD1/PDL1 inhibition in head and neck squamous cell carcinoma

Abstract

Background: Hyperprogressive disease (HPD) rate in head and neck squamous cell carcinoma (HNSCC) patients treated with immune checkpoint inhibitors (ICI) was determined using tumor growth kinetics (TGK) and compared with rapidly progressive screen-failure (SF) patients. The impact of TGK on outcomes with salvage chemotherapy (SCT) was also evaluated. Results: HPD was found in 22/120 (18%) patients. Median TGK before the onset of immunotherapy (TGK pre) was 2.7 for SF patients and 4.8 for HPD patients, with no significant difference (p = 0.17). Disease control rate after initial progressive disease on ICI was 86% with SCT in case of tumor growth deceleration vs 39% in case of tumor growth acceleration. Conclusions: HPD was frequent, but TGK of HPD patients treated with ICI did not differ from SF patients, suggesting that there is no relevant causal relationship between HPD and ICI. After initial PD with ICI, tumor growth deceleration was associated with better outcomes, indicating that TGK R might be useful to detect late responders, meriting prospective investigations. Materials and Methods: TGK ratio (TGK R) was defined as the ratio of TGK on ICI (TGK post) to TGK pre. HPD was defined as TGK R ≥ 2. TGK R >1 indicated tumor growth acceleration, while 0 < TGK R < 1 indicated tumor deceleration.

Hyperprogressive disease in patients suffering from solid malignancies treated by immune checkpoint inhibitors: A systematic review and meta-analysis

“…Illustrated by Figure 8 , a significant discrepancy was found among the five subgroups ( P = .02). The pooled incidence of HPD was 16.2% in patients suffering from gastrointestinal (GI) tract cancer ( n = 5, 95% CI, 10.4%–24.1%) ( 33 , 45 , 56 , 57 , 60 ); 14.4% in patients with NSCLC ( n = 14, 95% CI, 12.2%–17.0%) ( 13 , 16 , 17 , 21 , 29 , 34 , 42 – 44 , 51 , 54 , 59 , 62 , 63 ), 9.9% in patients with melanoma ( n = 3, 95% CI, 1.6%–43.4%) ( 35 , 36 , 53 ); 10.8% in patients with HCC ( n = 4, 95% CI, 8.4%–13.8%) ( 14 , 39 , 40 , 61 ); 18.06% in patients with HNC ( n = 6, 95% CI, 15.0%–21.6%) ( 15 , 37 , 38 , 48 , 49 , 52 ). Significant differences were found between these five tumor types (Q = 11.16, P = .0248), indicating that tumor type is a source of heterogeneity.…”

Systemic treatment of recurrent and/or metastatic squamous cell carcinomas of the head and neck: what is the best therapeutic sequence?

“…Out of the 34 patients who could be analyzed for the calculation of the tumor growth rate ratio (TGK R ), 10/34 (29%) had at least a doubling of the tumor growth rate under immunotherapy and this phenomenon seemed to be favored by locoregional recurrences. In a larger but single-center series [19], hyperprogression (measured with TGK r ≥ 2) was identified in 22 of 120 RM HNSCC patients (18%). A Korean retrospective study [20] reported data from 125 RM HNSCC patients of which 18 (14.4%) had at least a doubling of their TGK R .…”

“…In this heavily pretreated population, the ORR was equal to 30%, the clinical benefit (ORR þ stable disease) equal to 57% and the median OS equal to 7.8 months. Another series [19] of 67 RM HNSCC patients reported an ORR ¼ 28% and a clinical benefit rate ¼ 61% associated with salvage chemotherapy used after immunotherapy. In comparable settings, the ORR of Methotrexate was 6.7% in the LUX-HN1 trial [23], when the ORR associated with paclitaxel in the BERIL-1 trial [24] was 14%.…”

Current Understanding and Future Perspectives on Hyperprogressive Disease Highlight the Tumor Microenvironment

“…35 Furthermore, in terms of inflammatory indexes, dNLR and platelet count were higher in patients with HPD in both NSCLC and HNSCC. 78,79 An increase in NLR is not only accompanied by an increase in the risk of HPD, but NLR > 75% at week 4 predicted the occurrence of HPD with an accuracy of 86.1% in NSCLC. 56 Liquid Biopsy-Based Markers In addition, cell-free DNA (cfDNA) has been shown to be useful for assessing the response to treatment in cancer patients, detecting drug resistance, and predicting clinical outcomes as biomarkers, with the advantage that it can be isolated from plasma or serum in a noninvasive manner.…”

“…In the first large retrospective study of immune checkpoint inhibitors in the treatment of advanced melanoma, high baseline serum LDH in patients with HPD may suggest aggressive tumor biology 35 . Furthermore, in terms of inflammatory indexes, dNLR and platelet count were higher in patients with HPD in both NSCLC and HNSCC 78,79 . An increase in NLR is not only accompanied by an increase in the risk of HPD, but ΔNLR > 75% at week 4 predicted the occurrence of HPD with an accuracy of 86.1% in NSCLC 56 …”