Cancer Family
Lung Neoplasm
CI-CAN-00000221Explore in graph →
Non-malignant2,724 active trials51 approved drugs619 evidence items
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Cancer Family
CI-CAN-00000221Explore in graph →
Variants & evidence
1,284 evidence items mapped to this entity or its descendants, grouped by molecular profile, then therapy. 50 items per page.
| Therapy | Cancer | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|---|
| ALK Fusion2 | ||||||||
| Pemetrexed | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID945Among 95 patients with NSCLC in this study, 15 had an ALK translocation. ORR of these patients compared to EGFR mutated or wild-type tumors was superior (46.7 versus 4.7 versus 16.2%, p = 0.001). TYMS… (full text at CIViC) PMID 21642865 · Lee et al., 2011 · Open in CIViC | civic |
| Retaspimycin Hydrochloride | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 2 | accepted | EID1202In this study, heavily pretreated advanced NSCLC patients with various molecular tumor makeup were treated with Hsp90 inhibitor IPI-504 to assess overall response rate. The study did not reach the tar… (full text at CIViC) PMID 20940188 · Sequist et al., 2010 · Open in CIViC | civic |
| ALK I1171N + ALK Fusion1 | ||||||||
| Crizotinib | Lung Adenocarcinoma | Predictive | C | Supports Resistance | 2 | submitted | EID4633In a stage IV lung adenocarcinoma patient, ALK I1171N was associated with acquired resistance to crizotinib monotherapy. An ALK gene rearrangement had been previously identified and was associated wi… (full text at CIViC) PMID 27565911 · Johnson et al., 2016 · Open in CIViC | civic |
| ALK L1196M + ALK Fusion3 | ||||||||
| Ceritinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | submitted | EID7611A case study of a 58 year old woman with ALK-rearranged NSCLC found the resistance mutation L1196M following treatment with crizotinib and alectinib. Treatment with ceritinib resulted in tumour regres… (full text at CIViC) PMID 29796191 · Makuuchi et al., 2018 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 2 | submitted | EID2343In a prospective study (NCT01283516) of 130 cancer patients, non-small cell lung cancer patients (n=2) harboring a L1196M mutation in the ALK portion of the ALK rearrangement were associated with a 50… (full text at CIViC) PMID 24670165 · Shaw et al., 2014 · Open in CIViC | civic |
| Crizotinib | Lung Non-Small Cell Carcinoma | |||||||
| NRG1 Fusion1 | ||||||||
| Zenocutuzumab-zbco | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 4 | accepted | EID12246On December 4, 2024, the Food and Drug Administration granted accelerated approval to zenocutuzumab-zbco (Bizengri, Merus N.V.) for adults with advanced, unresectable, or metastatic non-small cell lun… (full text at CIViC) PMID 39908431 · Schram et al., 2025 · Open in CIViC | civic |
| NTRK1 Fusion2 | ||||||||
| Entrectinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | rejected | EID29471378 cases of NSCLC were screened. One patient (frequency 0.1%) with a NTRK1 gene rearrangement (SQSTM1-NTRK1 Fusion) was treated with entrectinib in a phase 1 study. The patient had resolution of pri… (full text at CIViC) PMID 26565381 · Farago et al., 2015 · Open in CIViC | civic |
| Crizotinib + Larotrectinib + LestaurtinibSubstitutes | Lung Adenocarcinoma | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID1019Two patients were found to harbor gene fusions maintaining the kinase domain of NTRK1 (3' partner), specifically: MPRIP-NTRK1 and CD74-NTRK1. Both of these fusions lead to constitutive kinase activit… (full text at CIViC) PMID 24162815 · Vaishnavi et al., 2013 · Open in CIViC | civic |
| RET Fusion9 | ||||||||
| Alectinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID4850Alectinib is an anaplastic lymphoma kinase tyrosine kinase inhibitor (TKI) that also has anti-RET activity in vitro. 4 patients with metastatic RET-rearranged NSCLC were identified. 3 of 4 had receive… (full text at CIViC) PMID 27544060 · Lin et al., 2016 · Open in CIViC | civic |
| Cabozantinib | Lung Adenocarcinoma | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID4847RET rearrangements are found in 1-2% of non-small-cell lung cancers. Cabozantinib is a multikinase inhibitor with activity against RET that produced a 10% overall response in unselected patients with … (full text at CIViC) PMID 27825636 · Drilon et al., 2016 · Open in CIViC | civic |
| Pralsetinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | ||||||
| ROS1 Fusion12 | ||||||||
| Ceritinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID11334In this phase II trial, 404 patients with advanced NSCLC underwent ROS1 pre-screening, and 32 patients with ROS1 rearrangement confirmed with FISH were enrolled. All patients except two were crizotini… (full text at CIViC) PMID 28520527 · Lim et al., 2017 · Open in CIViC | civic |
| Crizotinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID7282In the ongoing phase 1 study PROFILE 1001, NSCLC patients with ROS1 rearrangement confirmed by FISH or RT-PCR received crizotinib 250mg twice daily. Among 53 patients, the ORR was 72% (95% CI, 58% to … (full text at CIViC) PMID 30980071 · Shaw et al., 2019 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell Carcinoma | |||||||
| WEE1 RS39103841 | ||||||||
| Gemcitabine + Platinum CompoundCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID814The presence of the WEE1 polymorphism rs3910384 correlated with OS and PFS of NSCLC patients treated with platinum-based chemotherapy. Especially the combination of two DNA-damaging agents was associa… (full text at CIViC) PMID 26057002 · Liu et al., 2015 · Open in CIViC | civic |
| XRCC1 Q399R1 | ||||||||
| (prognostic) | Lung Non-Small Cell CarcinomaCURATED_BROADER | Prognostic | B | Supports Better Outcome | 4 | accepted | EID672The XRCC1 R399Q variant was significantly correlated with higher overall survival in non-small cell lung carcinoma (NSCLC) patients treated with gemcitabine and platinum. 62 patients with either Stage… (full text at CIViC) PMID 22551904 · Liao et al., 2012 · Open in CIViC | civic |
| XRCC1 R194W1 | ||||||||
| Docetaxel + Gemcitabine + VinorelbineSubstitutes | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID659The XRCC1 R194W variant was shown to be correlated with increased chance of response to platinum-based chemotherapy in Stage IV Non-small Cell Lung Carcinoma (NSCLC). 82 patients with Stage IV NSCLC w… (full text at CIViC) PMID 19157633 · Sun et al., 2009 · Open in CIViC | civic |
| YES1 Amplification + YES1 Overexpression1 | ||||||||
| CH6953755 + DasatinibSubstitutes | Lung Small Cell Carcinoma | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID12556In preclinical small cell lung carcinoma (SCLC) models with YES1 amplification or high expression, treatment with the YES1 inhibitor CH6953755 (30 mg/kg, q2d) or dasatinib (45 mg/kg daily) produced ma… (full text at CIViC) PMID 35988891 · Redin et al., 2022 · Open in CIViC | civic |
Data updated 11 hours agoSource updated unknownsource: civic (CC0)
Evidence levels, directions and ratings are those assigned by CIViC curators. "Submitted" items have not completed curation review. This is not treatment guidance.
| Predictive |
| C |
| Supports Resistance |
| 2 |
| submitted |
EID4035In a non-small cell lung cancer patient with a liver metastatic tumor harboring an ALK gene rearrangement and an ALK L1196M co-mutation, ALK L1196M was reported to be refractory to 7-month crizotinib … (full text at CIViC) PMID 23434628 · Huang et al., 2013 · Open in CIViC |
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| A |
| Supports Sensitivity Response |
| 4 |
| accepted |
EID11233In an open-label, phase 1/2 trial on 87 patients with NSCLC including RET-fusion were given 400 mg once-daily oral pralsetinib, with the outcome measured as overall response rate. Overall responses we… (full text at CIViC) PMID 34118197 · Gainor et al., 2021 · Open in CIViC |
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| Selpercatinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID11318In a follow up publication on the NCT03157128 clinical trial, results of 316 RET fusion positive NSCLC patients treated with the RET inhibitor selpercatinib were reported. Of note, this includes 144 … (full text at CIViC) PMID 36122315 · Drilon et al., 2023 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID7066In this phase 1 trial, 57 patients with RET fusion- or mutation positive cancers were treated in 7 dose levels. Among patients with RET-Fusion positive NSCLC, objective response rates were 65% (n = 17… (full text at CIViC) | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID8850Patients with RET-fusion positive non-small cell lung cancer were enrolled in this phase 1-2 trial of RET inhibitor selpercatinib. Among 105 consecutively enrolled patients who had previously received… (full text at CIViC) PMID 32846060 · Drilon et al., 2020 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID12135In this arm of the trial (NCT03157128), the intracranial objective response rate (iORR) was assessed in 80 patients with RET fusion-positive non-small cell lung cancer (NSCLC) treated with selpercatin… (full text at CIViC) PMID 34088726 · Subbiah et al., 2021 · Open in CIViC | civic |
| Vandetanib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID4848RET rearrangements involving RET are found in about 1% of NSCLC and define a unique molecular subset. This study was a multi-center, open-label, phase II clinical trial to examine the safety and effi… (full text at CIViC) PMID 27803005 · Lee et al., 2017 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID4849We aimed to assess the efficacy and safety of vandetanib in patients with advanced RET-rearranged NSCLC. In this open-label, multicentre, phase 2 trial (LURET), patients with advanced RET-rearranged N… (full text at CIViC) PMID 27825616 · Yoh et al., 2017 · Open in CIViC | civic |
| Predictive |
| A |
| Supports Sensitivity Response |
| 4 |
| accepted |
EID688An expansion cohort of a phase-1 Crizotinib study found a 72% objective response rate among 50 patients with ROS1 rearrangement. The study did not compare to patients without rearrangement that were t… (full text at CIViC) PMID 25264305 · Shaw et al., 2014 · Open in CIViC |
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| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 4 | accepted | EID7933A phase 2 clinical trial studied the efficacy of Crizotinib in East Asian NSCLC patients positive for ROS1 rearrangements (detected by RT-PCR AmoyDx assay) and negative for ALK1 rearrangements. Of the… (full text at CIViC) PMID 29596029 · Wu et al., 2018 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 3 | accepted | EID1030In a retrospective study, 30 patients were evaluated after crizotinib treatment for stage IV NSCLC confirmed for ROS1 rearrangement. On crizotinib, 24 of the patients achieved objective responses incl… (full text at CIViC) PMID 25667280 · Mazières et al., 2015 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 3 | submitted | EID8916The phase 2 EUCROSS trial (NCT02183870) examined the safety and efficacy of 250mg crizotinib twice daily in European ROS1-rearranged NSCLC patients. ROS1 status was assessed by break-apart FISH or bot… (full text at CIViC) PMID 30978502 · Michels et al., 2019 · Open in CIViC | civic |
| 〃 | Minimally Invasive Lung AdenocarcinomaALIAS | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID1443Study describes a 31-year old male, never-smoker patient with advanced NSCLC. Testing did not indicate tumor had EGFR mutation or ALK rearrangement. First line erlotininb did not yield a response. Aft… (full text at CIViC) PMID 22215748 · Bergethon et al., 2012 · Open in CIViC | civic |
| Entrectinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID11123Describes a meta-analysis of three separate phase I or II trials: ALKA-372-001, STARTRK-1, and STARTRK-2. All of these evaluate entrectinib in ROS-1 fusion-positive NSCLC (locally advanced or metastat… (full text at CIViC) PMID 31838015 · Drilon et al., 2020 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 3 | accepted | EID2951Two phase I studies included 119 patients with advanced or metastatic solid tumors, which included 28 patients with ROS1 rearrangements (n=28) where the overall safety and antitumor activity of entrec… (full text at CIViC) PMID 28183697 · Drilon et al., 2017 · Open in CIViC | civic |
| Lorlatinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID11335In this open-label, single-arm, phase 1-2 trial, 364 patients with histologically or cytologically confirmed advanced ROS1-positive NSCLC, with or without CNS metastases were assessed. Of them, 69 wit… (full text at CIViC) PMID 31669155 · Shaw et al., 2019 · Open in CIViC | civic |
| Repotrectinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID12021In a phase 1-2 trial (NCT03093116), the ROS1/ALK/NTRK inhibitor repotrectinib demonstrated efficacy in NSCLC with ROS1 fusions. Among the 71 ROS1-inhibitor-naive patients, 56 (79%; 95% CI, 68 to 88) h… (full text at CIViC) PMID 38197815 · Drilon et al., 2024 · Open in CIViC | civic |
| Taletrectinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID12240The TRUST-I study (NCT04395677) was a phase II, multicenter, single-arm, open-label trial conducted in China to evaluate taletrectinib for ROS1 fusion-positive, locally advanced, or metastatic non-sma… (full text at CIViC) PMID 38822758 · Li et al., 2024 · Open in CIViC | civic |