Subtype
Lung Carcinoma
CI-CAN-00001086Explore in graph →
2,130 active trials51 approved drugs598 evidence items
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Subtype
CI-CAN-00001086Explore in graph →
Variants & evidence
1,224 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 |
|---|---|---|---|---|---|---|---|---|
| TP53 Mutation1 | ||||||||
| Docetaxel + SelumetinibCombination | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID1145A clinical trial comparing selumetinib and docetaxel vs. docetaxel and placebo in KRAS mutant NSCLC was recapitulated in mice. Tumors were induced in lung epithelium by nasal instillation of CRE-beari… (full text at CIViC) PMID 22425996 · Chen et al., 2012 · Open in CIViC | civic |
| TP53 P72R1 | ||||||||
| (prognostic) | Lung Carcinoma | Prognostic | B | Does Not Support Poor Outcome | 3 | accepted | EID1303Pooled data from 13 studies of patients with lung cancer found little effect of codon 72 allele on the overall survival of patients with lung cancer. Proline homozygous patients were correlated with s… (full text at CIViC) PMID 12840112 · Matakidou et al., 2003 · Open in CIViC | civic |
| TP53 Wildtype1 | ||||||||
| Adjuvant Chemotherapy | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1149Pooled analysis of TP53 mutations (exons 5-8) from 4 randomized trials (IALT, JBR10, CALGB-9633 and ANITA, 1209 patients, median follow-up 5.5 years) of platinum-based adjuvant chemotherapy (ACT) vers… (full text at CIViC) PMID 26899019 · Ma et al., 2016 · Open in CIViC | civic |
| NTRK1 Fusion1 | ||||||||
| Larotrectinib | Lung Carcinoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID11692The goal of this study was to assess the efficacy and safety of larotrectinib in patients with TRK fusion–positive lung cancers. This was achieved by reviewing data from two global, multicenter clinic… (full text at CIViC) PMID 35085007 · Drilon et al., 2022 · Open in CIViC | civic |
| NTRK1 Fusion1 | ||||||||
| Larotrectinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID11744In the clinical trial NCT01775072, one patient had TPR::NTRK1 positive non-small cell lung cancer, and had a partial response with larotrectinib treatment before eventual progression. PMID 33004339 · Cocco et al., 2021 · Open in CIViC | civic |
| TTF1 AMPLIFICATION1 | ||||||||
| (prognostic) | Lung Adenocarcinoma | Prognostic | B | Does Not Support N/A | 3 | accepted | EID5276 of 89 patients with lung adenocarcinoma had amplification of TTF1. There was no statistical difference in overall survival between patients with and without gene amplification. PMID 19040416 · Barletta et al., 2009 · Open in CIViC | civic |
| TYMS Amplification1 | ||||||||
| Pemetrexed | Lung Adenocarcinoma | Predictive | B | Supports Resistance | 3 | accepted | EID903TYMS copy number was lower in clinical samples responding to pemetrexed in combination with platinum (n=25). The same was found in 17 cell lines. PMID 23645741 · Kasai et al., 2013 · Open in CIViC | civic |
| TYMS Overexpression2 | ||||||||
| Pemetrexed | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | 3 | accepted | EID832mRNA expression of thymidylate synthase (TYMS) in 62 NSCLC patients correlated with response rate to pemetrexed mono- or combination therapy. Response rate with low TYMS expression was 0.29 compared w… (full text at CIViC) PMID 26502926 · Chamizo et al., 2015 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Resistance | 3 | accepted | EID922mRNA levels of TYMS, DHFR and GARFT were assessed (rt-PCR) in 50 patient samples of NSCLC. TYMS mRNA levels were lower in responders compared to non-responders to pemetrexed (1.671 ± 0.844 versus 5.97… (full text at CIViC) PMID 23060591 · Shimizu et al., 2012 · Open in CIViC | civic |
| TYMS Underexpression1 | ||||||||
| Pemetrexed | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID90749 tumor specimens from 268 NSCLC patients treated with pemetrexed were evaluated for expression of TYMS and DHFR by IHC and compared to treatment outcomes. Patients with low TS (≤150) expression had … (full text at CIViC) PMID 21367480 · Chen et al., 2011 · Open in CIViC | civic |
| ALK Fusion32 | ||||||||
| Alectinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID1282In this Phase II trial of 87 patients (NCT01871805), alectinib was assayed for safety and efficacy in ALK positive NSCLC that had progressed on crizotinib. Of 69 patients with measurable disease, 35 a… (full text at CIViC) PMID 26708155 · Shaw et al., 2016 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID7284In a phase 3 trial, 303 patients with NSCLC with ALK fusion were randomly assigned to alectinib arm (N=152) or crizotinib arm (N=151). PFS was significantly longer with alectinib than with crizotinib … (full text at CIViC) PMID 28586279 · Peters et al., 2017 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell Carcinoma | |||||||
| 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 Fusion1 | ||||||||
| 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 |
Data updated 12 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 |
| A |
| Supports Sensitivity Response |
| 5 |
| submitted |
EID7533In this phase II study the safety, efficacy, and pharmacokinetics of twice daily 600mg alectinib treatment was assessed in 138 patients with advanced NSCLC harboring ALK rearrangements (previously det… (full text at CIViC) PMID 26598747 · Ou et al., 2016 · Open in CIViC |
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| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | submitted | EID7872National Comprehensive Cancer Network (NCCN) guidelines recommend alectinib for advanced ALK-positive NSCLC who are previously untreated or previously treated with crizotinib, including those with bra… (full text at CIViC) PMID 30030733 · Paik et al., 2018 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID8657A randomized phase 3 trial (J-ALEX) of 207 Japanese ALK-positive NSCLC patients compared the efficacy and safety of alectinib (300mg twice daily) and crizotinib (250mg twice daily) in the first-line s… (full text at CIViC) PMID 28501140 · Hida et al., 2017 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID12012In this global phase 3 trial, 257 patients with ALK-positive Non-Small-Cell Lung Cancer were treated with either alectinib (n = 130) or chemotherapy (n = 127). 93.8 % of the patients who had received … (full text at CIViC) PMID 38598794 · Wu et al., 2024 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1279In this Phase I trial (NCT01588028) in 47 patients, alectinib was assessed for its effectiveness in treating locally advanced or metastatic ALK-positive NSCLC that had progressed or been resistant to … (full text at CIViC) PMID 25153538 · Gadgeel et al., 2014 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1272In this initial report of a single-arm Phase I and II study (JapicCTI-101264) of alectinib (CH5424802), 46 patients with advanced or metastatic ALK-rearranged non small cell lung cancer (NSCLC) were a… (full text at CIViC) PMID 23639470 · Seto et al., 2013 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID1273In this case study of a critically ill 29 year old male nonsmoker with advanced metastatic ALK-positive NSCLC, alectinib (CH5424802), was administered as first line treatment. Where most clinical tria… (full text at CIViC) PMID 26938871 · Yoshida et al., 2016 · Open in CIViC | civic |
| Brigatinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID11121The phase III ALTA-1L open-label randomized trial examined 275 NSCLC patients given brigatinib (137 patients) vs crizotinib (138 patients). Patients were ALK fusion positive by an FDA-approved diagno… (full text at CIViC) PMID 32780660 · Camidge et al., 2020 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | rejected | EID1323Development of second generation ALK inhibitors has been underway in order to address resistance to first line treatments such as crizotinib in ALK-rearranged NSCLC. Brigatinib is a potent dual inhib… (full text at CIViC) PMID 26951079 · Wu et al., 2016 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID4835In a phase II randomized trial we evaluated two regimens of Brigatinib in Crizotinib-refractory ALK-pos. NSCLC. They were randomly assigned (1:1) to oral Brigatinib 90 mg once daily (arm A) or 180 mg … (full text at CIViC) PMID 28475456 · Kim et al., 2017 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID7053A single-arm, open-label, phase 1/2 trial showed that 51 (72% [60-82]) out of 71 patients with crizotinib-treated and crizotinib-naive ALK-rearranged NSCLC responded to the ALK inhibitor, Brigatinib. PMID 27836716 · Gettinger et al., 2016 · Open in CIViC | civic |
| Ceritinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID7285In a phase 3 trial, patients with previously treatmented NSCLC with ALK fusion were randomly assigned to ceritinib or chemotherapy. Ceritinib showed a significant improvement in median PFS compared w… (full text at CIViC) PMID 28602779 · Shaw et al., 2017 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID11190In a phase 3 trial (ASCEND-4, NCT01828099), a comparison of the selective ALK inhibitor ceritinib (750 mg daily) to chemotherapy (cisplatin or carboplatin plus pemetrexed) in 376 untreated ALK-fusion… (full text at CIViC) PMID 28126333 · Soria et al., 2017 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1175Updated results from ASCEND-1 trial assessing safety and activity of ceritinib in ALK rearranged locally advanced or metastatic NSCLC. 255 patients were enrolled and received at least one dose of ceri… (full text at CIViC) PMID 26973324 · Kim et al., 2016 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID7535This dose escalation phase 1 study examined the safety and efficacy of ceritinib in 122 NSCLC patients harboring ALK rearrangements (determined by break-apart FISH). Maximum tolerated dose (MTD) was d… (full text at CIViC) PMID 24670165 · Shaw et al., 2014 · Open in CIViC | civic |
| Crizotinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID1187In the Phase I study PROFILE 1001 (NCT00585195), a recommended crizotinib dose of 250 mg twice daily for 28 day cycles was established. Among 1,500 advanced NSCLC patients who were screened for ALK-re… (full text at CIViC) PMID 20979469 · Kwak et al., 2010 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID1198This two arm Phase III study named PROFILE 1007 (NCT00932893) was performed to assess crizotinib vs. established chemotherapy in non-small cell lung cancer patients positive for ALK rearrangement (ass… (full text at CIViC) PMID 23724913 · Shaw et al., 2013 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 5 | accepted | EID1199This phase 3 trial named PROFILE 1014 (NCT01154140) compared crizotinib to established chemotherapy in first-line treatment for this disease. The study consisted of 343 patients with advanced or metas… (full text at CIViC) PMID 25470694 · Solomon et al., 2014 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1200This retrospective study of patients from the PROFILE 1001 and 1005 studies of crizotinib in advanced ALK-rearranged NSCLC assessed the potential benefit of crizotinib beyond progressive disease (CBPD… (full text at CIViC) PMID 24478318 · Ou et al., 2014 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID1201This prospective Phase III study named Profile 1014 on NSCLC ALK-rearranged patients assessed intracranial disease control rate (IC-DCR) in the subset of patients entering the study with preexisting t… (full text at CIViC) PMID 27022118 · Solomon et al., 2016 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1419In a retrospective study comparing survival outcomes in a subgroup of 82 ALK-positive crizotinib-treated patients enrolled in a phase 1 clinical trial (NCT00585195), crizotinib therapy was associated … (full text at CIViC) PMID 21933749 · Shaw et al., 2011 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1577A phase-3 clinical trial evaluated 347 patients with ALK-positive lung cancer. The study compared crizotinib treatment (n=173) with chemotherapy treatment of either pemetrexed or docetaxel (n=174). … (full text at CIViC) PMID 26466010 · 2015 · Open in CIViC | civic |
| 〃 | Lung Adenocarcinoma | Predictive | C | Supports Sensitivity Response | 3 | accepted | EID1691In an evaluation of a patient with crizotinib-sensitive lung adenocarcinoma, an EML4-ALK-E13;A20 rearrangement was identified using CGP. The patient attained a reduction in the target lesions by 14.2… (full text at CIViC) PMID 25922291 · Le et al., 2015 · Open in CIViC | civic |
| Alectinib + CrizotinibSubstitutes | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 5 | accepted | EID4858In a randomized, open-label phase 3 trial 303 patients with ALK-positive, previously untreated NSCLC (including asympt. CNS disease) were randomized to reiceive either Alectinib or Crizotinib. During … (full text at CIViC) PMID 28586279 · Peters et al., 2017 · Open in CIViC | civic |
| Lorlatinib | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID11191In a phase 3 trial (CROWN, NCT03052608), a comparison of the selective third generation ALK inhibitor lorlatinib to the first generation ALK inhibitor crizotinib in 296 untreated ALK-fusion positive… (full text at CIViC) PMID 33207094 · Shaw et al., 2020 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID7286In a phase 2 trial, patients with NSCLC with ALK fusion received lorlatinib. In treatment-naive patients, ORR was 90.0% In patients with at least one previous ALK tyrosine kinase inhibitor, ORR were a… (full text at CIViC) PMID 30413378 · Solomon et al., 2018 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID7590A phase 2 trial of 228 ALK-positive NSCLC with or without previous chemotherapy treatment found lorlatinib to be effective in ALK inhibitor treatment-naive NSCLC as well as following treatment with on… (full text at CIViC) PMID 30413378 · Solomon et al., 2018 · Open in CIViC | civic |
| 〃 | Lung Non-Small Cell CarcinomaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID11192In a post hoc analysis of the phase 3 trial (CROWN, NCT03052608) comparing the selective third generation ALK inhibitor lorlatinib to the first generation ALK inhibitor crizotinib in ALK-fusion posit… (full text at CIViC) PMID 35605188 · Solomon et al., 2022 · Open in CIViC | civic |
| 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 |
| 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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