Treatment Beyond Progression with Immune Checkpoint Inhibitors in Non-Small-Cell Lung Cancer

Reinhorn, Daniel; Jacobi, Oded; Icht, Oded; Dudnik, Elizabeth; Rotem, Ofer; Zer, Alona; Goldstein, Daniel A.

doi:10.2217/imt-2019-0131

Cited by 19 publications

(21 citation statements)

References 16 publications

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“…To date, analyses of post-progression effects of anti-PD-1/PD-L1 agents in metastatic renal cell carcinoma [25,26] , melanoma [27,28] , and NSCLC [14,15] have already been reported. In the phase III OAK study, a prolonged median post-PD OS (12.7 months) was observed in atezolizumab-arm patients continuing TBP compared with patients switching to non-protocol therapy (8.8 months) and patients receiving no further therapy (2.2 months).…”

Section: Discussionmentioning

confidence: 99%

“…Seven percent of the atezolizumab TBP patients achieved a post-progression response in target lesions and 49% had stable disease [14] . In addition, a retrospective real-world study demonstrated that a substantial proportion of NSCLC patients who were clinically stable and judged to be eligible for TBP derived a significant survival benefit from TBP [15] . Of note, patients in these studies received TBP with the same treatment regimen and no additional treatment modality at progression, which was known as "classical" TBP [16] .…”

Section: Discussionmentioning

confidence: 99%

“…The efficacy of TBP was evaluated in NSCLC patients from clinical trials as well as real-world clinical practice [14][15][16][17] . Prolonged PFS and OS have been observed in the TBP group compared with those who were switched to other therapies, mostly chemotherapy, and those who received no further therapies.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Favorable clinical outcomes of checkpoint inhibitor-based combinations after progression with immunotherapy in advanced non-small cell lung cancer

Yu¹,

Chu²,

Wu³

et al. 2021

CDR

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Aim: Immune checkpoint inhibitors (ICIs) have dramatically changed the treatment paradigm in patients with nonsmall-cell lung cancer (NSCLC). However, progression patterns with immunotherapy are currently unclear and therapeutic options beyond resistance remain challenging. Methods:We reviewed advanced NSCLC patients between January 2016 and December 2019 who were treated with anti-PD-1/PD-L1 inhibitors in our center and identified those who developed disease progression. Later-line treatment strategies were collected and objective response rate, progression-free survival (PFS), and overall survival (OS) were assessed.Results: Of the 118 patients, 46 (39.0%) showed oligoprogression and 72 (61.0%) showed systemic progression. No difference in progression patterns was observed between monotherapy and combination therapy. Systemic progression was strongly associated with never-smokers (51.4% vs. 21.7%, P = 0.001) and ECOG PS = 2 (13.9% vs. 2.2%, P = 0.048) at baseline. The distribution of progression sites was roughly similar between oligoprogression and systemic progression, and the most commonly affected anatomic site was lung (66.9%), followed by bone Conclusion: Systemic progression occurs more frequently among NSCLC patients receiving ICIs. Checkpoint inhibitor-based combinations show favorable outcomes as subsequent treatment strategies after the failure of previous ICIs treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Favorable clinical outcomes of checkpoint inhibitor-based combinations after progression with immunotherapy in advanced non-small cell lung cancer

Yu¹,

Chu²,

Wu³

et al. 2021

CDR

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“…Tumor flare or pseudoprogression could result in early discontinuation of a treatment before it shows its true activity, even more if it is associated with a clinical benefit and it is well tolerated. Continuing the same treatment beyond radiological progression is a therapeutic strategy used in many types of tumors when the patient is experiencing clinical benefit, maintains a good performance status even in the presence of PD, and does not present symptomatic or critical progression in delicate sites of metastasis [ 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Tumor Growth Rate Decline despite Progressive Disease May Predict Improved Nivolumab Treatment Outcome in mRCC: When RECIST Is Not Enough

Mollica

Brocchi

Dall’Olio

et al. 2021

Cancers

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Treatment response is usually assessed by the response evaluation criteria in solid tumors (RECIST). These criteria may not be adequate to evaluate the response to immunotherapy, considering the peculiar patterns of response reported with this therapy. With the advent of immunotherapy these criteria have been modified to include the evaluation of the peculiar responses seen with this type of therapy (iRECIST criteria), including pseudoprogressions and hyperprogressions. Tumor growth rate (TGR) is a dynamic evaluation that takes into account the kinetics of response to treatment and may help catch the real efficacy of an immunotherapy approach. We performed a retrospective monocentric study to explore the impact of TGR change after nivolumab administration as the second or later line of treatment in patients with metastatic renal cell carcinoma (RCC). We evaluated 27 patients, divided into three categories: Disease control (DC) if there was no PD; lower velocity PD (LvPD) if disease progressed but the TGR at second assessment (TGR2) was lower than the TGR at first assessment (TGR1); higher velocity PD (HvPD) if TGR2 was higher than TGR1. The median OS for the DC group was 11.0 months (95% CI 5.0–17.0) (reference) vs. (not reached) NR (95% CI NR-NR) for LvPD (HR 0.27; 95% CI 0.06–1.30; p 0.102) vs. NR (95% CI NR–NR) for HvPD (HR 0.23; 95% CI 0.06–0.88; p 0.032). There was no difference between LvPD and DC (HR 1.21; 95% CI 0.20–7.28; p 0.838). In patients with metastatic RCC, the second or later line of nivolumab treatment may lead to a deceleration in TGR resulting in an improved survival outcome similar to that observed in patients experiencing tumor regression. In this subgroup, especially in the presence of a clinical benefit, continuing the treatment beyond progression can be recommended.

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“…An important issue is the optimal duration of treatment due to the potential of late treatment effect and the rare phenomenon of pseudoprogression. Many clinicians choose to continue treatment beyond progression with immunotherapy according to the RECIST[ 59 ]. As the progressing lesions might represent pseudoprogression, the monitoring and management of patients with the DR should be similar to that of patients with pseudoprogression, if the patient is clinically stable.…”

Section: Dissociated Responsementioning

confidence: 99%

Immune response evaluation criteria in solid tumors for assessment of atypical responses after immunotherapy

Ippolito¹,

Maino²,

Ragusi³

et al. 2021

WJCO

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In 2017, immune response evaluation criteria in solid tumors (iRECIST) were introduced to validate radiologic and clinical interpretations and to better analyze tumor’s response to immunotherapy, considering the different time of following and response, between this new therapy compared to the standard one. However, even if the iRECIST are worldwide accepted, to date, different aspects should be better underlined and well reported, especially in clinical practice. Clinical experience has demonstrated that in a non-negligible percentage of patients, it is challenging to determine the correct category of response (stable disease, progression disease, partial or complete response), and consequently, to define which is the best management for those patients. Approaching radiological response in patients who underwent immunotherapy, a new uncommon kind of target lesions behavior was found. This phenomenon is mainly due to the different mechanisms of action of immunotherapeutic drug. Therefore, new groups of response have been described in clinical practice, defined as “atypical responses,” and categorized into three new groups: pseudoprogression, hyperprogression, and dissociated response. This review summarizes and reports these patterns, helping clinicians and radiologists get used to atypical responses, in order to identify patients that respond best to treatment.

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Treatment Beyond Progression with Immune Checkpoint Inhibitors in Non-Small-Cell Lung Cancer

Cited by 19 publications

References 16 publications

Favorable clinical outcomes of checkpoint inhibitor-based combinations after progression with immunotherapy in advanced non-small cell lung cancer

Favorable clinical outcomes of checkpoint inhibitor-based combinations after progression with immunotherapy in advanced non-small cell lung cancer

Tumor Growth Rate Decline despite Progressive Disease May Predict Improved Nivolumab Treatment Outcome in mRCC: When RECIST Is Not Enough

Immune response evaluation criteria in solid tumors for assessment of atypical responses after immunotherapy

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