Efficacy of immune-checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC) patients harboring activating molecular alterations (ImmunoTarget).

Mazieres, Julien; Drilon, Alexander; Mhanna, Laurent; Milia, Julie; Lusque, Amellie; Cortot, A.; Mezquita, Laura; Thai, Alesha; Couraud, S.; Veillon, Rémi; Mascaux, Céline; Schouten, Robert D.; Neal, Joel W.; Ng, Terry L.; Frueh, M.; Peled, Nir; Gounant, V.; Popat, Sanjay; Zhu, Viola W.; Gautschi, Oliver

doi:10.1200/jco.2018.36.15_suppl.9010

Cited by 52 publications

(45 citation statements)

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“…The multi-centric retrospective ImmunoTarget trial (28) was designed to determine the sensitivity of NSCLC patients with oncogenic driver mutations to ICIs. Preliminary results have shown inconsistent efficacy among patients with driver mutations, but demonstrated superior results in patients with KRAS, BRAF and MET mutations compared to EGFR, ALK and RET alterations (29). KRAS data from this trial is still awaited.…”

Section: Discussionmentioning

confidence: 94%

The Activity of Immune Checkpoint Inhibition in KRAS Mutated Non-small Cell Lung Cancer: A Single Centre Experience

Torralvo

Friedlaender

Achard

et al. 2019

Cancer Genomics Proteomics

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Background/Aim: KRAS mutation is the most frequent molecular alteration found in advanced non-small cell lung cancer (NSCLC). It is associated with a poor prognosis without available targeted therapy. Treatment options for NSCLC have been recently enriched by the development of immune checkpoint inhibitors (ICIs), and data about their efficacy in patients with KRAS-mutant NSCLC are discordant. This study assessed the routine efficacy of ICIs in advanced KRAS-mutant NSCLC. Patients and Methods: All stage IV NSCLC patients treated in our institution from January 2016 to December 2017 with immunotherapy were included in our analysis. We collected the status of KRAS and other mutations, as well as the type of ICI administered. We assessed four clinical outcomes: i) disease control rate (DCR), ii) partial response (PR), iii) progression-free survival (PFS) and iv) overall survival (OS). Results: A total of 45 patients were initially identified but 7 were excluded due to insufficient clinical data, so 38 were included in the end. In the KRAS wildtype cohort, the DCR was 59% with 49% PR, while the PFS was 8.4 months and OS 16.8 months. Among KRAS mutated patients, results were more favourable, the DCR was 81%, with 62% PR. PFS was 13.6 months and OS was 18.5 months. The median follow-up was 24 months (17 to 34 months) and 7 patients were still on treatment at the time of analysis. Conclusion: Our data suggest that KRAS mutation is predictive of a superior response to immunotherapy. Furthermore, the lack of response of STK11 and KRAS co-mutated NSCLC patients to ICIs, is indeed negated by an additional TP53 mutation.

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Section: Discussionmentioning

confidence: 94%

The Activity of Immune Checkpoint Inhibition in KRAS Mutated Non-small Cell Lung Cancer: A Single Centre Experience

Torralvo

Friedlaender

Achard

et al. 2019

Cancer Genomics Proteomics

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“…Mazieres and Gautschi reported that patients with a MET mutation showed intermediate progression-free survival (3.4 months) after immunotherapy compared to those with other driver mutations, although PD-L1 and TMB status were not shown. 20 A therapeutic strategy for NSCLC with both high PD-L1 expression and driver mutation has not been established.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of pembrolizumab for patients with both high PD‐L1 expression and an MET exon 14 skipping mutation: A case report

et al. 2019

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Pembrolizumab has become the standard first‐line treatment for non‐small cell lung cancer (NSCLC) patients with high PD‐L1expression. MET exon 14 skipping is a rare mutation typically found in older, female, and non‐smoking patients with NSCLC. Herein, we report the case of a 71‐year‐old non‐smoking woman who was diagnosed with NSCLC in the left lung. EGFR mutation and ALK fusion were not detected. Because the biopsy specimen showed high PD‐L1 expression with a tumor proportion score of 95%, pembrolizumab was introduced as first‐line therapy, but resulted in no clinical benefit. The patient was subsequently administered chemotherapy with carboplatin and pemetrexed, leading to remarkable tumor shrinkage. A next‐generation sequencing panel analysis revealed a MET exon 14 skipping mutation. Thus, pembrolizumab might not be effective for NSCLC patients with MET exon 14 skipping mutations, even if PD‐L1 expression is high.

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“…Whether chemotherapy plus an immune checkpoint inhibitor would further prolong PFS in our patient population is unknown, but immune checkpoint inhibitor monotherapy is relatively ineffective in most never-smokers with oncogenic-driven tumors. 5 To our knowledge, there are no prospective studies or retrospective analyses evaluating afatinib in untreated patients with an HER2-driven lung cancer; however, 2 additional cases were identified ( Table 1). The first case is an account of a never-smoking female with a HER2 V659E mutation who had a confirmed PR for 5 months, and the second case described a female never-smoker with a HER2 pG776delinsVC who achieved a PR for 12þ months.…”

Section: Discussionmentioning

confidence: 99%

Durable Responses to Afatinib as First-line Therapy for HER2-mutated Metastatic Non–small-cell Lung Cancer

Al-Obeidi

Kelly

2020

Clinical Lung Cancer

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Efficacy of immune-checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC) patients harboring activating molecular alterations (ImmunoTarget).

Cited by 52 publications

References 0 publications

The Activity of Immune Checkpoint Inhibition in KRAS Mutated Non-small Cell Lung Cancer: A Single Centre Experience

The Activity of Immune Checkpoint Inhibition in KRAS Mutated Non-small Cell Lung Cancer: A Single Centre Experience

Efficacy of pembrolizumab for patients with both high PD‐L1 expression and an MET exon 14 skipping mutation: A case report

Durable Responses to Afatinib as First-line Therapy for HER2-mutated Metastatic Non–small-cell Lung Cancer

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