Impact of pseudoprogression and treatment beyond progression on outcome in patients with non-small cell lung cancer treated with immune checkpoint inhibitors

ABSTRACT

Background

Immune checkpoint inhibitors (ICI) have become an important treatment option for non-small cell lung cancer (NSCLC). We aimed to evaluate the clinical impact of pseudoprogression (PsP) and treatment beyond RECIST1.1-defined progressive disease (TBP) on outcome in NSCLC patients treated with ICI.

Methods

NSCLC patients treated with ICI between Mar 2016 and July 2018 were recruited in a consecutive manner. Response was assessed every 8–12 weeks using RECIST1.1 and iRECIST. Based on iRECIST, PsP was defined as progressive disease (PD) on RECIST1.1 subsequently reset to non-PD categories. Using log-rank test, progression-free survival (PFS) was compared between patients with and without PsP, and overall survival (OS) was compared between patients treated with and without TBP. The impact of TBP on OS was evaluated through multivariate Cox proportional hazard models.

Results

Of the 189 patients, seven (3.7%) experienced PsP which mostly occurred approximately 3 months after baseline. The median PFS was significantly longer in patients with PsP (not reached) than those without PsP (3.8 months, P = .02). Among patients who demonstrated PD according to RECIST1.1, median OS was significantly longer in patients with TBP (17.2 months) than those without TBP (7.4 months, P < .001). On multivariate analysis adjusting other covariates, TBP (HR, 0.4; 95% CI, 0.2–0.7) remained as a significant protective factor for mortality.

Conclusion

PsP occurred in 3.7% of NSCLC patients under ICI treatment. Based on iRECIST scheme, PsP and TBP may be associated with survival benefit.

KEYWORDS:

• Carcinoma
• Non-Small Cell Lung
• Immunotherapy
• Checkpoint inhibitor
• Response Evaluation Criteria In Solid Tumors
• Pseudoprogression

Acknowledgments

None

Author contribution

Conception and design of this article: Sang Eun Won, Hyo Jung Park, Sangil Byun, Junhee Pyo, Jwa Hoon Kim, Chang-Min Choi, Jae Cheol Lee, Dae Ho Lee, Sang-We Kim, Shinkyo Yoon, and Kyung Won Kim. Providing study material or patients: Sang Eun Won, Hyo Jung Park, Sangil Byun, Shinkyo Yoon, Kyung Won Kim. Collecting and/or assembling data: Sang Eun Won, Hyo Jung Park, Shinkyo Yoon, Kyung Won Kim. All authors participated in data analysis and interpretation, writing the article, and approved the final version.

Disclosure statement

The authors have declared that no competing interests, including financial interests, exist.

Precis

• Among patients with non-small cell lung cancer treated with immune checkpoint inhibitors, 3.7% (7/189) experienced pseudoprogression based on iRECIST scheme.

• Pseudoprogression and treatment beyond RECIST 1.1-defined disease progression may be associated with survival benefit in patients with non-small cell lung cancer treated with immune checkpoint inhibitors.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This research was supported by a grant of the Korea Health technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea. (Grant Number: HI18C2383).