KRAS G12C-mutant non-small-cell lung cancer: the decisions you may face

Cancer page →Second-opinion finder →

3 treatment settings, 3 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.

Advanced, first line

4 optionsCompare side by side →

As for driver-negative disease: pembrolizumab plus platinum doublet, or pembrolizumab alone if PD-L1 is 50 percent or more; KRAS inhibitors are not yet approved first line.

Guideline

NCCN Guidelines: Non-Small Cell Lung Cancer

The options, in plain words

PembrolizumabApprovedMonoclonal antibody (anti-PD-1)

Pembrolizumab is a PD-1 blocking antibody approved in more than 40 settings, from melanoma and lung cancer to the first tumour-agnostic approval for mismatch-repair-deficient tumours in 2017, and before and after surgery in triple-negative breast cancer. A subcutaneous form arrived in 2025, and it is the backbone partner for ADCs and personalised neoantigen vaccines.

CarboplatinApprovedCytotoxic chemotherapy (platinum)

Carboplatin is a platinum chemotherapy that crosslinks DNA; it is part of the standard pre-surgery regimen for triple-negative breast cancer.

PemetrexedApprovedCytotoxic (antifolate)

Pemetrexed is the chemotherapy that, with a platinum drug, became the first approved treatment for mesothelioma in 2004, and is still the backbone today.

Paclitaxel / nab-paclitaxelApprovedCytotoxic chemotherapy (taxane)

A microtubule poison discovered in the Pacific yew tree, among the most used chemotherapies in breast, lung, and ovarian cancer.

Also referenced:Tumour proportion score (TPS)

The evidence behind it

KEYNOTE-024 & KEYNOTE-189 Phase 3 NCT02142738 2016921 peopleevidence 95
Tests Pembrolizumab
First-line metastatic NSCLC without EGFR/ALK: pembrolizumab alone (PD-L1 TPS ≥50%, KEYNOTE-024) or pembrolizumab + platinum-pemetrexed (any PD-L1, non-squamous, KEYNOTE-189)
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
5-year OS 31.9% vs 16.3% (024); 19.4% vs 11.3% (189).
KEYNOTE-024: overall survival at 5 years, PD-L1 ≥50% (%): Pembrolizumab 31.9 (n=154) vs Chemotherapy 16.3 (n=151) · HR 0.62 · source

The main trade-offs on record

Pembrolizumab all recorded rates →

Side effect	Any grade	Grade 3+
Hypothyroidism (immune-mediated) · Pooled monotherapy data, >2,800 patients	8%	-
Pneumonitis (immune-mediated) · Pooled monotherapy data, >2,800 patients	3.4%	-
Colitis (immune-mediated) · Pooled monotherapy data, >2,800 patients	1.7%	-
Hepatitis (immune-mediated) · Pooled monotherapy data, >2,800 patients	0.7%	-

No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Carboplatin all recorded rates →

Dose by Calvert formula using GFR (see the calculators).

Pemetrexed all recorded rates →

Not recommended for CrCl below 45.

Questions to ask about this decision

Between Pembrolizumab, Carboplatin, Pemetrexed and the other options, which do you recommend for me, and what about my case would make you choose differently?
Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
Why: The aim shapes how much side effect and disruption is worth accepting.
How closely do I match the people in KEYNOTE-024 & KEYNOTE-189, and does that change what the results mean for me?
Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
Which side effects of Pembrolizumab are most likely for me, which are reversible, and which would make us stop?
Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
What happens if I delay, or decline this step for now? Is the decision reversible?
Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
Does your recommendation follow the current guideline (NCCN Guidelines: Non-Small Cell Lung Cancer), and if it departs from it, why?
Why: Departures from guidelines are sometimes right for an individual; they should be explained.
For my situation (advanced, first line), which of the standard options do you recommend and why?
Why: Guideline options include: As for driver-negative disease: pembrolizumab plus platinum doublet, or pembrolizumab alone if PD-L1 is 50 percent or more; KRAS inhibitors are not yet approved first line.
Am I a candidate for Pembrolizumab, Carboplatin, Pemetrexed or related drugs, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of KEYNOTE-024 & KEYNOTE-189 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Add these to your appointment list, or take the full question set for this cancer.

Advanced, first line

Advanced, after chemoimmunotherapy

5 optionsCompare side by side →

Sotorasib (CodeBreaK 200) or adagrasib (KRYSTAL-12), preferred to docetaxel; adagrasib for active brain metastases; docetaxel with or without ramucirumab afterwards.

Guideline

NCCN Guidelines: Non-Small Cell Lung Cancer

The options, in plain words

SotorasibApprovedSmall-molecule inhibitor (KRAS G12C)

Sotorasib (Lumakras) was the first drug to hit KRAS, approved in 2021 after four decades of failure.

AdagrasibApprovedSmall-molecule inhibitor (KRAS G12C)

Adagrasib was the second KRAS G12C inhibitor, with a long half-life and brain penetration, and is approved in lung and colorectal cancer.

DocetaxelApprovedCytotoxic chemotherapy (taxane)

The first chemotherapy to extend life in prostate cancer (2004), now part of triplet therapy at first metastatic diagnosis.

RamucirumabApprovedMonoclonal antibody (anti-VEGFR2)

An antibody that blocks the VEGF receptor, approved in liver cancer only for patients with a high AFP blood level, the first biomarker-selected HCC drug.

KRAS & RAS inhibitorsApproved

Drugs against the most common cancer gene, considered impossible to target until sotorasib in 2021.

First drugs for a 40-year-old target

The evidence behind it

CodeBreaK 200 Phase 3 NCT04303780 2022345 peopleevidence 87
Tests Sotorasib
Previously treated KRAS G12C NSCLC: sotorasib vs docetaxel
PFS HR 0.66; OS HR 1.01.
Progression-free survival (BICR) (months): Sotorasib 5.6 (n=171) vs Docetaxel 4.5 (n=174) · HR 0.66 · source
KRYSTAL-12 Phase 3 NCT04685135 2024453 peopleevidence 87
Tests Adagrasib
Previously treated KRAS G12C NSCLC: adagrasib vs docetaxel
PFS HR 0.58.
Progression-free survival (BICR) (months): Adagrasib 5.5 (n=301) vs Docetaxel 3.8 (n=152) · HR 0.58 · source

The main trade-offs on record

Sotorasib all recorded rates →

Side effect	Any grade	Grade 3+
Hepatotoxicity · CodeBreaK 100	25%	12%
Interstitial lung disease · CodeBreaK 100	2.2%	1.1%
Diarrhoea · CodeBreaK 100	42%	-
Musculoskeletal pain · CodeBreaK 100	35%	-

No adjustment for mild impairment; hepatotoxicity is common and worse after recent immunotherapy.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Adagrasib all recorded rates →

Side effect	Any grade	Grade 3+
Hepatotoxicity · KRYSTAL-1 NSCLC	37%	10%
Dyspnoea · KRYSTAL-1 NSCLC	35%	10%
Fatigue · KRYSTAL-1 NSCLC	59%	7%
Musculoskeletal pain · KRYSTAL-1 NSCLC	41%	7%

Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Docetaxel all recorded rates →

Do not give if bilirubin above ULN, or AST/ALT above 1.5 x ULN with alkaline phosphatase above 2.5 x ULN (treatment-related deaths).

KRAS & RAS inhibitors

Modest durability as monotherapy
Adaptive RTK feedback requires combinations

Questions to ask about this decision

Between Sotorasib, Adagrasib, Docetaxel and the other options, which do you recommend for me, and what about my case would make you choose differently?
Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
Why: The aim shapes how much side effect and disruption is worth accepting.
How closely do I match the people in CodeBreaK 200 and KRYSTAL-12, and does that change what the results mean for me?
Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
Which side effects of Sotorasib or Adagrasib are most likely for me, which are reversible, and which would make us stop?
Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
What happens if I delay, or decline this step for now? Is the decision reversible?
Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
Does your recommendation follow the current guideline (NCCN Guidelines: Non-Small Cell Lung Cancer), and if it departs from it, why?
Why: Departures from guidelines are sometimes right for an individual; they should be explained.
For my situation (advanced, after chemoimmunotherapy), which of the standard options do you recommend and why?
Why: Guideline options include: Sotorasib (CodeBreaK 200) or adagrasib (KRYSTAL-12), preferred to docetaxel; adagrasib for active brain metastases; docetaxel with or without ramucirumab afterwards.
Am I a candidate for Sotorasib, Adagrasib, Docetaxel or related drugs, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of CodeBreaK 200 and KRYSTAL-12 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Add these to your appointment list, or take the full question set for this cancer.

Advanced, first line

Advanced, clinical trials

3 optionsCompare side by side →

Divarasib versus sotorasib or adagrasib (Krascendo 1); olomorasib or adagrasib with pembrolizumab first line (SUNRAY-01, KRYSTAL-7); pan-RAS inhibitors.

Guideline

NCCN Guidelines: Non-Small Cell Lung Cancer

The options, in plain words

DivarasibPhase 3Small-molecule inhibitor (KRAS G12C)

Divarasib is Roche's KRAS G12C pill, the first to beat the two approved KRAS drugs head-to-head (July 2026).

OlomorasibPhase 3Small-molecule inhibitor (KRAS G12C)

Olomorasib is Lilly's KRAS G12C pill, designed to combine safely with immunotherapy in first-line lung cancer.

DaraxonrasibApprovedSmall-molecule pan-RAS(ON) inhibitor

The first drug that blocks all active RAS variants, approved by the FDA in August 2026 for metastatic pancreatic cancer, where KRAS drives 90% of tumours.

The evidence behind it

Krascendo 1 Phase 3 NCT06497556 2026338 peopleevidence 87
Tests Divarasib
Previously treated KRAS G12C NSCLC: divarasib vs sotorasib or adagrasib
Superior PFS and OS vs approved G12C inhibitors (topline, July 2026).
A Study of First-Line Olomorasib (LY3537982) and Pembrolizumab With or Without Chemotherapy in Patients With Advanced KRAS G12C-Mutant Non-small Cell Lung Cancer Phase 3 NCT061195811,264 peopleevidence 51
Tests Olomorasib
SUNRAY-01, A Global Pivotal Study in Participants With KRAS G12C-Mutant, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Comparing First-Line Treatment of LY3537982 and Pembrolizumab vs Placebo and Pembrolizumab in Those With PD-L1 Expression ≥50% or LY3537982 and Pembrolizumab, Pemetrexed, Platinum vs Placebo and Pembrolizumab, Pemetrexed, Platinum Regardless of PD-L1 Expression
No headline result recorded yet.
Phase 2 Trial of Adagrasib Monotherapy and in Combination With Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination in Patients With a KRAS G Phase 2/3 NCT04613596626 peopleevidence 41
A Phase 2 Trial of Adagrasib Monotherapy and in Combination With Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination With Pembrolizumab Versus Pembrolizumab in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation
No headline result recorded yet.

The main trade-offs on record

No side-effect rates or interaction flags are recorded for these options yet. The side-effect lookup and interaction checker cover the products that have them.

Questions to ask about this decision

Between Divarasib, Olomorasib and Daraxonrasib, which do you recommend for me, and what about my case would make you choose differently?
Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
Why: The aim shapes how much side effect and disruption is worth accepting.
How closely do I match the people in Krascendo 1 and A Study of First-Line Olomorasib (LY3537982) and Pembrolizumab With or Without Chemotherapy in Patients With Advanced KRAS G12C-Mutant Non-small Cell Lung Cancer, and does that change what the results mean for me?
Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
What happens if I delay, or decline this step for now? Is the decision reversible?
Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
Does your recommendation follow the current guideline (NCCN Guidelines: Non-Small Cell Lung Cancer), and if it departs from it, why?
Why: Departures from guidelines are sometimes right for an individual; they should be explained.
For my situation (advanced, clinical trials), which of the standard options do you recommend and why?
Why: Guideline options include: Divarasib versus sotorasib or adagrasib (Krascendo 1); olomorasib or adagrasib with pembrolizumab first line (SUNRAY-01, KRYSTAL-7); pan-RAS inhibitors.
Am I a candidate for Divarasib, Olomorasib, Daraxonrasib, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of Krascendo 1 and A Study of First-Line Olomorasib (LY3537982) and Pembrolizumab With or Without Chemotherapy in Patients With Advanced KRAS G12C-Mutant Non-small Cell Lung Cancer apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Add these to your appointment list, or take the full question set for this cancer.

How to read this page. Options and results come from OnCo records with their sources; the settings are the standard-of-care rows on the cancer page, and the lines of therapy are on the sequencing grid. Where a setting names one path, the choice is usually about timing, trials and where to be treated: see expert centres. OnCo is orientation, not medical advice.