Post-progression outcomes of NSCLC patients with PD-L1 expression ≥ 50% receiving first-line single-agent pembrolizumab in a large multicentre real-world study

Cortellini, Alessio; Cannita, Katia; Tiseo, Marcello; Cortinovis, Diego; Aerts, Joachim; Baldessari, Cinzia; Giusti, Raffaele; Ferrara, Miriam Grazia; D’Argento, Ettore; Grossi, Francesco; Guida, Annalisa; Berardi, Rossana; Morabito, Alessandro; Genova, Carlo; Antonuzzo, Lorenzo; Mazzoni, Francesca; Toma, Alessandro De; Signorelli, Diego; Targato, Giada; Rastelli, Francesca; Chiari, Rita; Rocco, Danilo; Gori, Stefania; Tursi, Michele De; Mansueto, Giovanni; Zoratto, Federica; Filetti, Marco; Bracarda, Sergio; Citarella, Fabrizio; Russano, Marco; Cantini, Luca; Nigro, Olga; Buti, Sebastiano; Minuti, Gabriele; Landi, Lorenza; Ricciardi, Serena; Migliorino, Maria Rita; Natalizio, Salvatore; Carnio, Simona; Filippis, Marco De; Metro, Giulio; Adamo, Vincenzo; Russo, Alessandro; Spinelli, Gian Paolo; Maïo, Massimo Di; Banna, Giuseppe Luigi; Friedlaender, Alex; Addeo, Alfredo; Pinato, David J.; Ficorella, Corrado; Porzio, Giampiero

doi:10.1016/j.ejca.2021.02.005

Cited by 21 publications

(13 citation statements)

References 33 publications

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“…However, the median PPS of 15.3 months achieved by patients whose change to TKI therapy was deferred beyond initial evidence of progression to ICI is a provocative finding and compares favourably to survival estimates of patients who were treated with immediate switching to TKI. Continuation of ICI beyond the first point of progression is commonplace in clinical practice and often permitted in clinical trials of ICI, recognising the potential for cancer immunotherapy to alter tumour biology beyond strict radiological criteria 29 and allowing, in other tumour types, deferred switch to potentially less tolerable strategies such as chemotherapy 30,31 or TKIs. 32 To our knowledge, our study is the first to report on the clinical use of immunotherapy beyond RECIST progression in HCC and suggests that this strategy should be investigated in a subset of patients with advanced disease, potentially based on the radiographic characteristics of progression.…”

Section: Discussionmentioning

confidence: 99%

Progression patterns and therapeutic sequencing following immune checkpoint inhibition for hepatocellular carcinoma: An international observational study

Talbot

D’Alessio

Pinter

et al. 2023

Liver International

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Background and Aims Different approaches are available after the progression of disease (PD) to immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC), including the continuation of ICI, treatment switching to tyrosine kinase inhibitors (TKIs) and cessation of anticancer therapy. We sought to characterise the relationship between radiological patterns of progression and survival post‐ICI, also appraising treatment strategies. Methods We screened 604 HCC patients treated with ICIs, including only those who experienced PD by data cut‐off. We evaluated post‐progression survival (PPS) according to the treatment strategy at PD and verified its relationship with radiological patterns of progression: intrahepatic growth (IHG), new intrahepatic lesion (NIH), extrahepatic growth (EHG), new extrahepatic lesion (NEH) and new vascular invasion (nVI). Results Of 604 patients, 364 (60.3%) experienced PD during observation. Median PPS was 5.3 months (95% CI: 4.4–6.9; 271 events). At the data cut‐off, 165 patients (45%) received no post‐progression anticancer therapy; 64 patients (17.6%) continued ICI beyond PD. IHG (HR 1.64 [95% CI: 1.21–2.22]; p = .0013) and nVI (HR 2.15 [95% CI: 1.38–3.35]; p = .0007) were associated with shorter PPS. Multivariate models adjusted for progression patterns, treatment line and albumin‐bilirubin grade and Eastern Cooperative Oncology Group performance status at PD confirmed receipt of ICI beyond PD with (HR 0.17, 95% CI: 0.09–0.32; p < .0001) or without subsequent TKI (HR 0.39, 95% CI: 0.26–0.58; p < .0001) as predictors of prolonged PPS versus no anticancer therapy. Conclusions ICI‐TKI sequencing is a consolidated option in advanced HCC. nVI and IHG predict a poorer prognosis. Despite lack of recommendation, the continuation of ICI beyond progression in HCC is adopted clinically: future efforts should appraise which patients benefit from this approach.

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Section: Discussionmentioning

confidence: 99%

Progression patterns and therapeutic sequencing following immune checkpoint inhibition for hepatocellular carcinoma: An international observational study

Talbot

D’Alessio

Pinter

et al. 2023

Liver International

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“…An analysis of KEYNOTE-047, which randomized patients with metastatic NSCLC to either pembrolizumab + chemotherapy or placebo + chemotherapy found a median time to first progression of 8.0 months and median time to second progression of just 13.8 months from the initiation of treatment in the pembrolizumab group [ 30 ]. Another May 2021 multicenter analysis of patients with NSCLC and PD-L1 expression ≥50% who progressed on first line pembrolizumab monotherapy found that those patients who received local ablative treatments lived longer after progressing than those who switched systemic therapy or continued on pembrolizumab alone (overall survival of 13.9 months versus 8.0 months versus 8.2 months, respectively) [ 31 ]. Lastly, in the aforementioned CURB trial, the median PFS was just 10 weeks in the palliative standard of care arm versus 22 weeks in the SBRT arm; however, it should be noted that systemic therapy was given per the treating physician’s discretion and immunotherapy was not required for enrollment [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Oligoprogression of Solid Tumors on Immune Checkpoint Inhibitors: The Impact of Local Ablative Radiation Therapy

et al. 2022

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The breakthrough of a limited number of clones while on immune checkpoint inhibitors (ICIs), known as oligoprogression, has been previously described. The benefit of ablative radiation therapy (RT) directed at these clones, as opposed to changing systemic therapy, is unclear. We analyzed 30 patients with advanced solid tumors, the majority of whom (23/30, 86.7%) had either hepatocellular or urothelial carcinoma, who experienced oligoprogression on ICIs and were referred for RT. In this study, oligoprogression was defined as having experienced progression at three or fewer metastatic sites outside of the brain after achieving at least stable disease on ICIs for a minimum of three months. The median time to oligoprogression was 11.1 months from the initiation of immunotherapy. 24 patients had one oligoprogressive lesion and six had two. The median radiation dose delivered was 4650 cGy in a median of five fractions. The median progression-free survival (PFS) after RT was 7.1 months, and the time to oligoprogression was not a significant predictor of PFS2. 26 patients continued on ICIs after RT. While 17 patients subsequently progressed, 15 did so at three or fewer metastatic sites and could have theoretically stood to benefit from an additional course of salvage RT to further extend the lifespan of their ICIs. Overall survival at 6, 12, and 24 months was 100.0%, 96.3%, and 82.8%, respectively. These results suggest that RT may provide a PFS benefit and extend the lifespan of ICIs in patients who experience oligoprogression. Regardless of PFS, however, overall survival in this population appears to be excellent.

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“…Moreover, the increasing prevalence of patients with cancer aged 70 years or older will inevitably enhance the discrepancy between the characteristics of patients enrolled in clinical trials and those of the patients who are treated in the everyday clinical practice. Among these latter, a higher level of treatment attrition may for example be observed, as well a worse PS [91].…”

Section: Discussionmentioning

confidence: 99%

The use of immunotherapy in older patients with advanced non-small cell lung cancer

Tagliamento

Frélaut

Baldini

et al. 2022

Cancer Treatment Reviews

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Post-progression outcomes of NSCLC patients with PD-L1 expression ≥ 50% receiving first-line single-agent pembrolizumab in a large multicentre real-world study

Cited by 21 publications

References 33 publications

Progression patterns and therapeutic sequencing following immune checkpoint inhibition for hepatocellular carcinoma: An international observational study

Progression patterns and therapeutic sequencing following immune checkpoint inhibition for hepatocellular carcinoma: An international observational study

Oligoprogression of Solid Tumors on Immune Checkpoint Inhibitors: The Impact of Local Ablative Radiation Therapy

The use of immunotherapy in older patients with advanced non-small cell lung cancer

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