Hyperprogressive disease (HPD) during nivolumab (Nivo) or irinotecan (IRI) as salvage line in patients with metastatic gastric cancer (MGC).

126 Background: Nivo was approved in heavily treated MGC patients in September 2017 in Japan. HPD have been reported in patients with various tumor types treated with anti-PD-1/PD-L1 antibody therapy, but no data was existed in gastric cancer. Methods: We retrospectively compared tumor growth kinetics (TGK) on Nivo or IRI as salvage line and TGK on last treatment in patients with MGC in our hospital. The TGK ratio (TGKR, ratio of the slope of tumor growth before treatment and the slope of tumor growth on treatment) was calculated. HPD was defined as a TGKR ≥ 2. Results: 51 patients have been treated Nivo (n = 31) or IRI (n = 20) as salvage line before Aug 2018 in our hospital. The median age was 67 years (range 37-81) in Nivo and 68 years (range 46-80) in IRI.; 20 males and 11 females in Nivo and 16 males and 4 females in IRI; PS 0-1/2 score 19/12 in Nivo and 19/1 in IRI. Thirty-five patients (Nivo : IRI = 16:19) had target lesions according to RECIST 1.1 and performed CT pre, baseline and during treatment. HPD were observed in seven patients (44%) with Nivo. On the contrary, only one patient (5%) experienced HPD with IRI. Median PFS and OS (HPD vs. non-HPD) were 2.1 versus 3.5 months (HR: 0.29 (0.083-0.98), p = 0.046) and 5.3 versus 6.6 months (HR: 0.44 (0.078-2.5), p = 0.35) with Nivo. The rate of grade3-4 irAEs were colitis (6%), interstitial pneumonia (6%), and mytosis (3%) with Nivo. No treatment-related death and pseudo-progression were observed. Conclusions: HPD is more common with Nivo compared with IRI in patients with MGC as salvage line and associated with poor PFS in patients treated with Nivo. Further analysis will be warranted.

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Hyperprogression after Immunotherapy: Nivolumab. Analysis of Imaging Findings Associated with Hyperprogression and Tumor Growth Kinetics

Indian Journal of Radiology and Imaging ◽

10.1055/s-0041-1734341 ◽

2021 ◽

Author(s):

Rishu Singla ◽

Ayushi Gupta ◽

Ullas Batra ◽

Arvind Chaturvedi ◽

Avinash Rao ◽

...

Keyword(s):

Tumor Growth ◽

Growth Kinetics ◽

Checkpoint Inhibitors ◽

Antibody Therapy ◽

Case Series ◽

Progression Free Survival ◽

Rapid Progression ◽

Imaging Findings ◽

Pleural Thickening ◽

Tumor Growth Kinetics

Abstract Introduction The increased use of new checkpoint inhibitors in cancer therapy has led to the discovery of new unconventional responses, like pseudoprogression and hyperprogression disease (HPD). The study documents imaging findings of HPD and analyzes the growth kinetics in advanced metastatic cancers patients treated with immunotherapy. Methods We retrospectively reviewed patients treated with anti-PD-1 (anti-progressive disease-1) antibody therapy (nivolumab) between January 2017 and December 2017 at our institute. The patients who exhibited early and rapid progression rates after initiation of immunotherapy were further analyzed for tumor growth kinetics (TGKs) and imaging findings. All prebaseline, baseline, and post nivolumab imaging were retrospectively reviewed to assess the TGKs, time to treatment failure (TTF), and rate of progression according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Results Four patients with HPD had peculiar imaging appearance of unilateral circumferential nodular pleural thickening along with conglomerate pleural masses and effusions. Both primary and secondary sites progressed along with the appearance of new lesions in all these patients. The mean progression-free survival (PFS) was 32 days using Kaplan Meier analysis. Conclusion The unique and recurring imaging pattern of disease progression in patients with HPD as reported in our case series in addition to TGK ratio, and TTF may prove to be of additional help in early identification of this unique and ghastly outcome.

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