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Every dated change on the records linked to Non-small-cell lung cancer, newest first: approvals and regulatory steps on its medicines, trials that reported, guideline versions, milestones, and when this page itself was checked. Dates come from the records; none is inferred. Orientation, not medical advice.
Untreated advanced EGFR mutation-positive non-small-cell lung cancer (exon 19 deletion or L858R), with lazertinib
Untreated advanced non-small-cell lung cancer with an activating EGFR exon 20 insertion, with carboplatin and pemetrexed
Aumseqa: first-line advanced NSCLC with EGFR exon 19 deletion or L858R; advanced EGFR T790M-positive NSCLC
Untreated locally advanced non-small-cell lung cancer unsuitable for definitive chemoradiation, or metastatic disease, with PD-L1 in 1 percent or more of tumour cells and no EGFR or ALK alteration, with platinum-based chemotherapy
Untreated advanced EGFR mutation-positive non-small-cell lung cancer (exon 19 deletion or L858R), with amivantamab
Resectable non-small-cell lung cancer at high risk of recurrence without an EGFR mutation or ALK rearrangement: neoadjuvant with platinum chemotherapy then adjuvant alone
Unresectable stage III EGFR mutation-positive non-small-cell lung cancer that has not progressed after platinum-based chemoradiotherapy
ROS1+ NSCLC (July 2026)
First-line HER2-mutant non-squamous NSCLC
Objective response 64 percent after platinum chemotherapy and 85 percent in previously untreated RET fusion-positive non-small-cell lung cancer; intracranial response 91 percent.
At the final analysis (median follow-up 38.
Interim PFS not statistically significant (May 2026); final readouts pending.
Superior PFS and OS vs approved G12C inhibitors (topline, July 2026).
Second-line daraxonrasib 300 mg in 26 patients with RAS G12-mutated pancreatic cancer: objective response 35 percent, median progression-free survival 8.
A milestone in how this cancer is treated.
EGFR-mutant NSCLC after TKI and platinum chemotherapy (accelerated) The confirmatory requirement was still open 1.2 years later, when the FDA's table was read.
Full approval in NSCLC (KRYSTAL-12)
Accelerated approval, previously treated c-MET-high non-squamous NSCLC (LUMINOSITY) The confirmatory requirement was still open 1.3 years later, when the FDA's table was read.
HER2-mutant NSCLC
Adjuvant treatment of resected non-small-cell lung cancer after platinum chemotherapy, where PD-L1 is on 50 percent or more of tumour cells and the tumour is not EGFR-mutant or ALK-positive
EGFR-mutant NSCLC after EGFR TKI and platinum chemotherapy
Resectable non-small-cell lung cancer (4 cm or more, or node positive) without an EGFR mutation or ALK rearrangement, neoadjuvant with platinum chemotherapy then adjuvant alone
1L EGFR-mutant NSCLC with amivantamab; 20 Jan 2025
ALK-positive advanced non-small-cell lung cancer not previously treated with an ALK inhibitor
Adjuvant treatment of stage IB to IIIA EGFR exon 19 deletion or L858R non-small-cell lung cancer after complete resection
Untreated advanced EGFR mutation-positive non-small-cell lung cancer, with pemetrexed and platinum-based chemotherapy
Adjuvant treatment of non-small-cell lung cancer at high risk of recurrence after complete resection and platinum chemotherapy
ROS1+ NSCLC; NTRK+ solid tumours; 13 Jan 2025 (conditional)
With osimertinib in EGFR-mutant NSCLC with MET amplification after EGFR TKI (SACHI)
Previously treated RET fusion-positive advanced non-small-cell lung cancer not previously treated with a RET inhibitor
HER2 TKD-mutant non-squamous NSCLC after prior systemic therapy (accelerated)
Locally advanced/metastatic NSCLC with EGFR exon 20 insertions after platinum
ROS1-positive NSCLC
Locally advanced or metastatic ROS1-positive NSCLC
c-MET-high non-squamous NSCLC, previously treated (accelerated)
HER2-mutant NSCLC after ≥1 systemic therapy (May 2025)
HER2-mutant NSCLC, previously treated (accelerated)
Objective response 30 percent across 158 evaluable NRG1 fusion-positive cancers, 42 percent (15 of 36) in pancreatic cancer; median duration of response 11.
ORR 31% in heavily pretreated ALK+ NSCLC; NDA under priority review.
Confirmed response rate 71% in 75 previously treated patients naive to HER2-directed therapy; 48% after a HER2 antibody-drug conjugate; FDA accelerated approval August 2025.
PFS HR 0.
ORR ~64%; accelerated approval Nov 2025.
261 lung cancers in 12,773 participants, 79.
PLCOm2012 at 1.
A milestone in how this cancer is treated.
Accelerated approval, NRG1-fusion NSCLC and pancreatic adenocarcinoma (eNRGy): first therapy for NRG1 fusions The confirmatory requirement was still open 1.8 years later, when the FDA's table was read.
Breakthrough Therapy designation, EGFR-mutant NSCLC after TKI
KRAS G12C NSCLC after ≥1 line; 5 Jan 2024 (conditional)
Adjuvant ALK+ NSCLC after resection (stage IB ≥4 cm to IIIA)
First-line EGFR-mutant NSCLC with lazertinib
ROS1-positive advanced non-small-cell lung cancer in patients who have not had a ROS1 inhibitor
ALK-positive locally advanced or metastatic NSCLC, ALK-inhibitor-naive
KRAS G12C-mutant advanced NSCLC after at least one systemic therapy
KRAS G12C-mutant advanced NSCLC after at least one systemic therapy
EGFR-mutant NSCLC after TKI (with chemotherapy); first-line PD-L1+ NSCLC
First-line EGFR exon 19 del / L858R NSCLC with amivantamab
Locally advanced or metastatic EGFR T790M-mutant non-small cell lung cancer after prior EGFR inhibitor therapy
Metastatic NSCLC after platinum with PD-1 or docetaxel
Resectable non-small-cell lung cancer at high risk of recurrence, neoadjuvant with platinum chemotherapy then adjuvant alone
Pretreated advanced TNBC; later EGFR-mutant NSCLC after TKI
First-line metastatic NSCLC with platinum chemotherapy, no sensitising EGFR, ALK, ROS1 or RET alterations
NRG1-fusion NSCLC and pancreatic adenocarcinoma
Eighteen-month event-free survival 70.
PFS HR 0.
PFS 7.
PFS HR 0.
PFS HR 0.
ORR 28.
Concurrent durvalumab with chemoradiotherapy did not significantly improve progression-free survival over chemoradiotherapy alone.
Placebo-adjusted weight gain 2.
A milestone in how this cancer is treated.
BRAF V600E metastatic NSCLC with encorafenib
BRAF V600 mutation-positive advanced non-small-cell lung cancer, first line only
ALK-positive non-small-cell lung cancer after crizotinib; first line from 2024
Neoadjuvant treatment of resectable non-small-cell lung cancer (4 cm or more, or node positive), with chemotherapy
ROS1+ locally advanced or metastatic NSCLC
Untreated RET fusion-positive advanced non-small-cell lung cancer
EGFR exon 20 insertion NSCLC after platinum
Perioperative durvalumab with neoadjuvant platinum chemotherapy improved event-free survival (hazard ratio 0.
DFS HR 0.
5-year disease-free survival 63.
Confirmed response rate 49.
PFS HR 0.
EFS HR 0.
PFS HR 0.
Weight gain over 5%: 60% vs 9%; appetite improvement 43% vs 13%.
PFS HR 0.
Response rate 75% (treatment-naive, n=59) and 46% (previously treated, n=39); FDA approval October 2023.
Copy-number heterogeneity predicted recurrence or death with a hazard ratio of 4.
PFS HR 0.
ORR 43.
A milestone in how this cancer is treated.
In the trials of pembrolizumab with chemotherapy, continuous tissue mutational burden predicts nothing in either histology, and neither do STK11, KEAP1 or KRAS status.
Neoadjuvant NSCLC with chemotherapy (CheckMate 816)
Complete response letter for ORIENT-11 (first-line non-squamous NSCLC); ODAC voted 14 to 1 that additional data were needed for US applicability
KRAS G12C NSCLC (accelerated)
Locally advanced or metastatic non-small-cell lung cancer with an EGFR exon 20 insertion after platinum-based chemotherapy: not recommended
Locally advanced unresectable non-small-cell lung cancer with PD-L1 on 1 percent or more of cells that has not progressed after concurrent platinum-based chemoradiation
First-line EGFR exon 19 deletion or L858R NSCLC (FURLONG)
Untreated metastatic squamous non-small-cell lung cancer, with carboplatin and paclitaxel
RET fusion-positive advanced non-small-cell lung cancer in patients who have not had a RET inhibitor: not recommended
Companion diagnostic for adagrasib in KRAS G12C-mutant NSCLC (plasma)
KRAS G12C mutation-positive locally advanced or metastatic non-small-cell lung cancer that has progressed on, or after intolerance of, platinum-based chemotherapy or PD-1/PD-L1 immunotherapy
Unresectable stage III NSCLC without progression after chemoradiotherapy (GEMSTONE-301)
Advanced non-small-cell lung cancer with MET exon 14 skipping alterations
Advanced NSCLC with MET exon 14 skipping alterations after immunotherapy or platinum chemotherapy
HER2-low metastatic breast cancer; HER2-mutant NSCLC
Metastatic NSCLC without EGFR/ALK, with durvalumab and platinum chemotherapy; unresectable HCC with durvalumab
PFS 19.
EFS HR 0.
PFS HR 0.
High response rate with durable responses in HER2-mutant non-small-cell lung cancer; accelerated approval in August 2022.
PFS 20.
PFS 7.
Median overall survival 14.
Durvalumab with chemotherapy improved progression-free survival (5.
Physical function at five weeks 4.
A milestone in how this cancer is treated.
Accelerated approval, KRAS G12C NSCLC after ≥1 therapy: first KRAS inhibitor The confirmatory requirement was still open 5.3 years later, when the FDA's table was read.
Accelerated approval, EGFR exon 20 insertion NSCLC after platinum
EGFR exon 20 insertion NSCLC
Untreated metastatic non-small-cell lung cancer with PD-L1 on at least 50 percent of tumour cells or 10 percent of tumour-infiltrating immune cells and no EGFR or ALK alteration
First-line EGFR exon 19 deletion or L858R NSCLC (AENEAS)
ALK-positive advanced non-small-cell lung cancer not previously treated with an ALK inhibitor
EGFR T790M-positive locally advanced or metastatic NSCLC after EGFR TKI therapy
Adjuvant treatment of resected stage II to IIIA EGFR-mutant NSCLC (EVIDENCE)
Untreated metastatic non-small-cell lung cancer, with nivolumab and two cycles of platinum doublet chemotherapy: not recommended
First-line ALK+ NSCLC
EGFR exon 20 insertion NSCLC after platinum
Locally advanced or metastatic PD-L1-positive non-squamous non-small-cell lung cancer after chemotherapy
Untreated metastatic non-small-cell lung cancer without an EGFR or ALK alteration, with ipilimumab and two cycles of platinum doublet chemotherapy: not recommended
510(k) clearance: AI decision support for indeterminate pulmonary nodules
Untreated metastatic non-squamous non-small-cell lung cancer without an EGFR or ALK alteration, with pemetrexed and platinum chemotherapy
MET exon 14 skipping NSCLC after platinum chemotherapy or unfit for chemotherapy (conditional; later full)
First-line non-squamous NSCLC with pemetrexed and platinum (ORIENT-11); first-line squamous NSCLC with gemcitabine and platinum (ORIENT-12); first-line unresectable hepatocellular carcinoma with IBI305 (ORIENT-32)
KRAS G12C NSCLC, previously treated (accelerated)
First-line metastatic squamous and non-squamous NSCLC with platinum chemotherapy (GEMSTONE-302)
Metastatic NSCLC with MET exon 14 skipping alterations
Companion diagnostic for adjuvant atezolizumab in PD-L1 TC ≥1% resected NSCLC
ORR 71% (naive MTC), 89% (RET-fusion thyroid).
PFS 11.
Amivantamab produced durable responses in EGFR exon 20 insertion non-small-cell lung cancer after platinum chemotherapy; accelerated approval in May 2021.
Median overall survival not reached vs 14.
Median progression-free survival 25.
Nivolumab plus ipilimumab did not improve survival over nivolumab alone; the trial closed for futility.
IMpower010: adjuvant atezolizumab after platinum chemotherapy improved disease-free survival in resected stage II to IIIA non-small-cell lung cancer, most in tumours with PD-L1 on 1 percent or more of tumour cells (hazard ratio 0.
42 cancers in 1,994 people scanned, 85.
Whole genomes of 232 never-smoker lung cancers find no tobacco signature and three copy-number subtypes, one of them slow-growing with driver progenitor cells dating back many years.
A milestone in how this cancer is treated.
EGFR T790M-positive locally advanced or metastatic NSCLC after EGFR TKI therapy
First-line ALK-positive metastatic NSCLC
MET exon 14 skipping NSCLC (capmatinib; tepotinib 2021)
Metastatic NSCLC with a MET exon 14 skipping mutation (accelerated approval)
ALK-positive NSCLC after crizotinib
ROS1-positive advanced non-small-cell lung cancer in patients who have not had a ROS1 inhibitor
Companion diagnostic for osimertinib (EGFR) in NSCLC; first liquid comprehensive genomic profiling test
ALK-positive advanced non-small-cell lung cancer progressing after alectinib or ceritinib as the first ALK inhibitor, or after crizotinib and at least one other ALK inhibitor
Locally advanced or metastatic squamous non-small-cell lung cancer after chemotherapy
CE mark
Untreated locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer
EGFR T790M mutation-positive locally advanced or metastatic non-small-cell lung cancer after a first-line EGFR inhibitor
Adjuvant EGFR-mutant NSCLC
RET-fusion metastatic NSCLC (full approval 2023)
RET-fusion NSCLC and thyroid; RET-mutant MTC
Unresectable advanced or recurrent NSCLC with MET exon 14 skipping
OS HR 0.
Median overall survival 14.
5-year PFS 60% vs 8%, HR 0.
PFS 16 vs 8 months (HR 0.
Response rate 68% (treatment-naive, n=28) and 41% (previously treated, n=69) in MET exon 14 skipping disease; about a third in high-level MET amplification.
In the PD-L1-highest subgroup, median overall survival 20.
Genotype-matched targeted arms (taselisib, palbociclib, AZD4547) closed for futility; nivolumab plus ipilimumab did not beat nivolumab (S1400I); ramucirumab plus pembrolizumab improved overall survival against standard care (S1800A).
Most of the 22 biomarker-drug cohorts did not meet their pre-set efficacy thresholds; the trial demonstrated national molecular screening and the limits of single-agent matching.
PFS 8.
Continuous cohort reporting: positive signals for pembrolizumab in high tumour mutational burden cancers and trastuzumab plus pertuzumab in ERBB2-amplified colorectal cancer; palbociclib in CDKN2A-altered lung cancer and several other matches were negative.
Independent-review objective response 46% (95% CI 36 to 57) among 99 patients with at least nine months of follow-up; median duration of response 11.
A milestone in how this cancer is treated.
Metastatic non-squamous non-small-cell lung cancer, with bevacizumab, carboplatin and paclitaxel
ALK-positive advanced non-small-cell lung cancer after crizotinib
Classical Hodgkin lymphoma; subsequently HCC, NSCLC, ESCC (second line 2020, first line with chemotherapy 2021), nasopharyngeal
Untreated locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer
ROS1-positive metastatic NSCLC; NTRK fusion solid tumours (≥12 years, extended to ≥1 month 2023)
Multi-gene companion diagnostic system for NSCLC
Classical Hodgkin lymphoma (first); subsequently urothelial, NSCLC, HCC, ESCC, gastric, nasopharyngeal
Nivolumab plus ipilimumab improved overall survival over chemotherapy in PD-L1-positive advanced non-small-cell lung cancer; approved in the United States in May 2020.
Local failure hazard ratio 0.
Median overall survival 20.
No clear stage shift (54.
5-year OS 42.
Transcription factor expression splits small-cell disease into four subtypes; in parallel, cell-free DNA is shown to be non-inferior to tissue genotyping at diagnosis and six days faster.
Untreated ALK-positive advanced non-small-cell lung cancer
Advanced NSCLC after at least two lines of systemic therapy (ALTER 0303)
Locally advanced or metastatic non-small-cell lung cancer after chemotherapy
ALK-positive NSCLC
Untreated ALK-positive advanced non-small-cell lung cancer
First-line metastatic NSCLC with EGFR exon 19 del or L858R
Unresectable stage III NSCLC after chemoradiation
BRAF V600E-mutant metastatic colorectal cancer, with cetuximab
ALK+ NSCLC after prior ALK TKI
First-line EGFR-mutant NSCLC
Untreated PD-L1-positive metastatic non-small-cell lung cancer with a tumour proportion score of 50 percent or more and no EGFR or ALK alteration
Median progression-free survival 24.
OS 9.
Median progression-free survival 18.
Median progression-free survival 8.
Pembrolizumab plus carboplatin and a taxane improved overall and progression-free survival over chemotherapy alone across PD-L1 levels; approved in October 2018.
STK11 and KEAP1 are tied to poor immunotherapy outcomes in KRAS-mutant disease; the College of American Pathologists, the International Association for the Study of Lung Cancer and the Association for Molecular Pathology require ROS1 testing for all adenocarcinomas and allow plasma to rule a mutation in but not out.
A milestone in how this cancer is treated.
First-line ALK+ NSCLC
ALK-positive metastatic NSCLC after crizotinib
First-line ALK-positive metastatic NSCLC
BRAF V600E metastatic NSCLC
Companion diagnostic for BRAF, ROS1 and EGFR-directed therapies in NSCLC
Locally advanced or metastatic PD-L1-positive non-small-cell lung cancer after at least one chemotherapy
Median progression-free survival 34.
Confirmed objective response rate 45% (90 mg) and 54% (180 mg after a 7-day 90 mg lead-in); median progression-free survival 9.
Median total hospital days 10.
Median progression-free survival 14.
Median progression-free survival 16.
Median progression-free survival 4.
OS HR 0.
The Blueprint comparison shows three PD-L1 assays agree on tumour cells and SP142 does not. Of 860 patients with metastatic lung adenocarcinoma sequenced prospectively, 37.1% received a matched therapy, and the limiting factor was the evidence behind each alteration rather than detection; transformation to small-cell carcinoma is shown to branch from the adenocarcinoma clone before treatment begins.
A milestone in how this cancer is treated.
Squamous NSCLC after platinum
Urothelial carcinoma (later withdrawn); NSCLC
v2: T790M for osimertinib; plasma testing (first liquid biopsy companion diagnostic)
ROS1-positive metastatic NSCLC
EGFR-expressing locally advanced or metastatic squamous NSCLC with gemcitabine and cisplatin
Locally advanced or metastatic non-small-cell lung cancer progressing after platinum-based chemotherapy, with docetaxel: not recommended
PD-L1 expression to inform atezolizumab treatment in urothelial carcinoma (later NSCLC)
Median overall survival 10.
5-year OS 31.
Median overall survival 13.
Quality-adjusted life-years 46.
Lean body mass increased (about +1 to +1.
Across 103 repeat biopsies, each ALK inhibitor is shown to select its own spectrum of resistance mutations, with G1202R rising after second-generation treatment and the presence of a mutation predicting benefit from the third generation.
ALK+ NSCLC after crizotinib
First-line NSCLC with EGFR exon 19 del or L858R
First-line metastatic squamous NSCLC with gemcitabine and cisplatin
CE mark (GBM); pancreatic and NSCLC CE marks 2024-26
EGFR T790M NSCLC
Companion diagnostic for pembrolizumab in NSCLC (TPS)
Median overall survival 9.
Median overall survival 12.
3-year overall survival 76.
Median overall survival 28.
Overall survival significantly longer with necitumumab added to gemcitabine and cisplatin, by roughly six weeks at the median; hypomagnesaemia, rash and thromboembolism were the added toxicities.
CheckMate 017/057; pembrolizumab first line for PD-L1 ≥50% follows (KEYNOTE-024, 2016).
Biallelic TP53 and RB1 loss in nearly all of 110 small-cell genomes, with NOTCH inactivation in 25%; in the same year, non-synonymous mutation burden is shown to predict response to PD-1 blockade in lung cancer, and KRAS-mutant disease is split into immune-poor and inflamed subsets by its co-mutations.
ALK-positive metastatic NSCLC after crizotinib
With trametinib: BRAF V600E/K metastatic melanoma; later adjuvant melanoma, BRAF V600E NSCLC, anaplastic thyroid cancer, tumour-agnostic solid tumours and paediatric low-grade glioma
First-line EGFR-mutant NSCLC
Gastric cancer; NSCLC
BRAF V600 melanoma alone or with dabrafenib; later NSCLC and adjuvant melanoma
With dabrafenib: metastatic melanoma; later adjuvant melanoma, NSCLC, anaplastic thyroid cancer, tumour-agnostic BRAF V600E solid tumours, paediatric low-grade glioma
Median progression-free survival 3.
Median overall survival 10.
Two hundred and thirty adenocarcinomas profiled on every platform add RIT1 and MGA to the driver list and show that NF1, MET, ERBB2 and RIT1 drive the tumours with no other oncogene; the Lung Cancer Mutation Consortium finds a driver in 64% of 733 patients and longer survival where treatment matched it.
First-line metastatic NSCLC with EGFR exon 19 del or L858R
EGFR exon 19 deletion / L858R companion diagnostic for erlotinib (v1)
BRAF V600 melanoma; later NSCLC and adjuvant melanoma with trametinib
First-line NSCLC with EGFR exon 19 del or L858R
therascreen EGFR: afatinib in EGFR-mutant NSCLC
Rebiopsy of 155 patients: T790M in 63%, MET amplification in 5%, HER2 amplification in 13% and small-cell transformation in 3%, making rebiopsy at progression standard.
No significant difference in breathlessness over 42 days (24.
TP53 mutated in nearly all of 178 squamous tumours, with the NFE2L2 and KEAP1 pathway altered in 34%, squamous differentiation genes in 44% and CDKN2A with RB1 in 72%; ROS1 rearrangements are defined as a class in 1,073 screened patients.
ALK-positive metastatic NSCLC
Advanced NSCLC after failure of at least one chemotherapy regimen (ICOGEN)
Lung cancer mortality reduced 20% (NLST) and 24% in men (NELSON).
A milestone in how this cancer is treated.
Soda et al.; crizotinib approved 2011.
MET amplification restores the growth signal through ERBB3 in 4 of 18 lung cancers resistant to an EGFR inhibitor, defining bypass resistance as a category.
NSCLC; later ovarian, cervical, RCC, glioblastoma, HCC
Median survival 7.
Advanced non-small-cell lung cancer, with vinorelbine and cisplatin
EGFR T790M is found in a patient relapsing after two years on gefitinib, and independently in progressing tumours that had not carried it before treatment. It becomes the most studied resistance mutation in cancer.
Locally advanced/metastatic NSCLC after chemotherapy
In advanced disease, chemotherapy gave a hazard ratio for death of 0.
Pain response to initial treatment 71 percent after a single 8 Gy fraction against 73 percent after 24 Gy in multiple fractions (p=0.
Lynch, Paez, and Pao identify activating EGFR mutations; the birth of lung cancer precision medicine.