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. 2020 Apr 23;12(4):1046.
doi: 10.3390/cancers12041046.

Oligoprogressive Non-Small-Cell Lung Cancer under Treatment with PD-(L)1 Inhibitors

Stephan Rheinheimer  1   2 , Claus-Peter Heussel  1   2   3 , Philipp Mayer  1   2 , Lena Gaissmaier  4 , Farastuk Bozorgmehr  1   4 , Hauke Winter  1   5 , Felix J Herth  1   6 , Thomas Muley  1   7 , Stephan Liersch  8 , Helge Bischoff  1   4 , Mark Kriegsmann  1   9 , Rami A El Shafie  10 , Albrecht Stenzinger  1   9 , Michael Thomas  1   4 , Hans-Ulrich Kauczor  1   2   3 , Petros Christopoulos  1   4
Affiliations

Oligoprogressive Non-Small-Cell Lung Cancer under Treatment with PD-(L)1 Inhibitors

Stephan Rheinheimer et al. Cancers (Basel). .

Abstract

Oligoprogression (OPD) of non-small-cell lung cancer (NSCLC) occurs in approximately half of patients under targeted compounds (TKI) and facilitates use of regional therapies that can prolong survival. In order to characterize OPD in immunotherapy (IO)-treated NSCLC, we analyzed the failure pattern under PD-1/PD-L1 inhibitors (n = 297) or chemoimmunotherapy (n = 75). Under IO monotherapy, OPD was more frequent (20% vs. 10%, p < 0.05), occurred later (median 11 vs. 5 months, p < 0.01), affected fewer sites (mean 1.1 vs. 1.5, p < 0.05), and involved fewer lesions (1.4 vs. 2.3, p < 0.05) in the first compared to later lines. Lymph nodes (42%, mainly mediastinal) and the brain (39%) were mostly affected, followed by the lung (24%) and other organs. Compared to multifocal progression, OPD occurred later (11 vs. 4 months, p < 0.001) and was associated with longer survival (26 vs. 13 months, p < 0.001) and higher tumor PD-L1 expression (p < 0.001). Chemoimmunotherapy showed a similar incidence of OPD as IO monotherapy (13% vs. 11% at 2 years). Local treatments were applied regularly for brain but only in 50% for extracranial lesions. Thus, NSCLC oligoprogression is less common under IO than under TKI, but also favorable. Since its frequency drops later in the disease, regular restaging and multidisciplinary evaluation are essential in order to exploit the full therapeutic potential.

Keywords: chemoimmunotherapy; immunotherapy; local therapy; non-small-cell lung cancer; oligoprogression.

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Conflict of interest statement

Dr. Heussel reports consultation, lecture and other fees from Novartis, Basilea, Bayer, Grifols, Boehringer, Pierre Fabre, Covidien, Siemens, Chiesi, Intermune, MEDA Pharma, Bracco, Pfizer, MSD, Roche, Lilly, AstraZeneca, Schering-Plough, Essex, Gilead, MeVis, Fresenius, Astellas as well as ownership of GSK stocks; Dr. Herth reports advisory board fees and honoraria from Lilly, Roche, AstraZeneca, Novartis, Boehringer, Chiesi, Teva, Pulmonx BTG and Olympus as well as research funding from Lilly, Roche, AstraZeneca, Novartis, Boehringer, Chiesi and Teva; Dr. Stenzinger reports advisory board honoraria and/or speaker fees: Astra Zeneca, Bayer, Eli Lilly, Roche, BMS, Illumina, MSD, Novartis, Pfizer, Seattle Genetics, Takeda, Thermo Fisher, and research grants from BMS, Bayer and Chugai; Dr. Thomas reports advisory board honoraria from Novartis, Lilly, BMS, MSD, Roche, Celgene, Takeda, AbbVie, Boehringer, speaker’s honoraria from Lilly, MSD, Takeda, research funding from AstraZeneca, BMS, Celgene, Novartis, Roche and travel grants from BMS, MSD, Novartis, Boehringer. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
CONSORT diagram of the study.
Figure 2
Figure 2
Lymph node oligoprogression. A 66-year-old male patient with adeno-NSCLC (PD-L1 90%) was started on pembrolizumab in November 2017. Nodal progression on the right side was noted in June 2018, which appeared stable in a subsequent restaging in October 2018, even though no change in therapy occurred.
Figure 3
Figure 3
Lung oligoprogression and transitional cell carcinoma of the kidney. A 75-year-old female with adeno-NSCLC (PD-L1 90%) was started on pembrolizumab in September 2017 with response of the primary tumor, mediastinal lymph nodes, and liver metastases. Upon oligoprogression of the primary tumor in March 2018, thoracic radiotherapy was administered. In August 2018, a new kidney lesion was noted that grew oligoprogressive-like. At biopsy, this lesion turned out to be a transitional-cell carcinoma.
Figure 4
Figure 4
Incidence and prognosis of oligoprogression during first-line immunotherapy (to the right). (A) Cumulative incidence of oligoprogression (OPD) in stage IV NSCLC under first-line IO monotherapy (n = 163) vs. first-line chemoimmunotherapy (n = 106) in the entire study population (Figure 1). Patients without disease progression were censored, while OPD and diffuse progression were considered as competing risks. Cumulative incidence at 2 years was 12.6% for chemoimmunotherapy-treated vs. 11.0% for IO-monotherapy-treated patients (Gray’s p = 0.99). (B) Time-to-progression for NSCLC patients developing OPD (n = 18) vs. diffuse disease progression (n = 71) under first-line IO monotherapy (Table 1, log-rank p < 0.001). (C) Overall survival (OS) of NSCLC patients developing OPD (n = 18) vs. diffuse disease progression (n = 71), under first-line IO monotherapy (Table 1, log-rank p < 0.001).
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