CodeBreaK 200: Sotorasib Offers Improved Quality of Life for Patients With Previously Treated NSCLC

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The latest research on sotorasib, a targeted therapy for KRAS G12C–mutated non–small cell lung cancer (NSCLC), reveals that patients may experience better quality of life while benefiting from improved clinical outcomes. Analysis of patient-reported outcomes presented during the European Lung Cancer Congress 2023 showed significantly improved symptom severity and quality of life with sotorasib vs docetaxel in patients with KRAS G12C–mutated locally advanced or metastatic NSCLC who had received at least one prior systemic therapy.1

The first-in-class KRAS G12C inhibitor sotorasib already had accelerated or full approval in nearly 50 countries, including the United States and the European Union, based on the phase III global randomized CodeBreaK 200 study, which demonstrated significantly improved progression-free survival in this setting with sotorasib vs docetaxel.2 According to the study authors, however, these updated findings should provide reassurance that the improved outcomes do not come at the expense of symptom severity or interference in daily life.

“Sotorasib significantly improved quality of life compared to docetaxel, suggesting this treatment may be a more tolerable treatment option for patients with previously treated non–small cell lung cancer who have the KRAS G12C mutation,” said lead study author David M. Waterhouse, MD, a hematology/oncology specialist at Dana-Farber Cancer Institute, Boston.

David M. Waterhouse, MD

David M. Waterhouse, MD

As Dr. Waterhouse reported, several treatment options are available for patients with NSCLC, but conventional therapies often come with significant side effects and may not provide substantial benefits in terms of survival or quality of life. Targeted therapies, such as KRAS G12C inhibitors like sotorasib, aim to provide more effective and tolerable treatment options for patients with specific genetic mutations.

CodeBreaK 200: Study Methods

CodeBreaK 200 was a phase III, multinational, multisite clinical study designed to assess the efficacy and safety of sotorasib in comparison with the standard of care, docetaxel, in patients with KRAS G12C–mutated advanced NSCLC who had previously been treated with chemotherapy and immunotherapy. The primary endpoint of the study was progression-free survival, with secondary endpoints including overall response rate, disease control rate, time to response, and duration of response.

Patients were randomly assigned to receive either oral sotorasib at 960 mg daily or standard-of-care docetaxel at a conventional 75 mg/m2 every 3 weeks. Previously reported outcomes demonstrated significantly improved progression-free survival with sotorasib vs docetaxel.

In addition to the primary endpoint, patient-reported outcomes were assessed as secondary endpoints. These outcomes were measured using multiple questionnaires, including the Functional Assessment of Cancer Therapy–General form (FACT-G), Patient-Reported Outcome–Common Terminology Criteria for Adverse Events (PRO-CTCAE), and EuroQoL–5 Dimension (EQ-5D).

Less Symptom Severity

Compared with patients receiving docetaxel, those receiving sotorasib were less bothered by their side effects (odds ratio [OR] = 5.71) and experienced symptoms at a lower severity at week 12.

“Throughout most of these different domains, we saw that toxicity had a greater impact in the docetaxel arm and that patients on the sotorasib arm tended to fare better and were less severely bothered by their side effects over time,” Dr. Waterhouse reported. Other domains, including global pain severity, muscle aching severity, and joint pain severity, also favored the sotorasib arm with respect to severity.

In addition to symptom severity, analysis of patient-reported outcomes showed that patients treated with sotorasib experienced less interference in their daily activities compared with those treated with docetaxel. Patients on the sotorasib arm also demonstrated improved mobility, self-care, and ability to perform usual activities.


  • Earlier reports from the phase II CodeBreaK 200 study demonstrated significantly improved progression-free survival with sotorasib vs docetaxel in patients with previously treated KRAS G12C–mutated NSCLC.
  • A new analysis of patient-reported outcomes from the study showed less symptom severity and improved quality of life with sotorasib vs docetaxel.

The safety profile of sotorasib was generally favorable compared with docetaxel. Although the frequency of side effects was similar between the two treatment groups, said Dr. Waterhouse, patients on the sotorasib arm were less bothered by the side effects and experienced less severe symptoms. The most common adverse events reported in the sotorasib arm were diarrhea, nausea, and fatigue, whereas the docetaxel arm reported more neutropenia, fatigue, and hair loss.

“We knew sotorasib improved progression-free survival as well as secondary endpoints, including response rates, disease control rate, and duration of response, but we were not sure how that translated into the patient experience,” said Dr. Waterhouse, who emphasized that the use of multiple questionnaires allowed for a comprehensive assessment. “This analysis clearly shows improved quality of life with sotorasib vs docetaxel.”

“Being patient-centric and patient-focused is important,” added Dr. Waterhouse, regarding the importance of incorporating patient-reported outcomes into clinical trials. “We should be doing more of it.” 

DISCLOSURE: Dr. Waterhouse reported financial relationships with BMS, AstraZeneca, Amgen, Janssen, EMD, Serono, Merck, Jazz Pharmaceuticals, Exelixis, Eisai, Pfizer, Mirati, Regeneron/Sanofi, Fresenius Kabi, Eli Lilly, Sanofi, Astellas, and Gilead Sciences.


1. Waterhouse DM: Sotorasib shows improved quality of life over docetaxel in NSCLC patients. European Lung Cancer Congress 2023. Abstract 40. Presented March 29, 2023.

2. de Langen AJ, Johnson ML, Mazieres J, et al: Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRASG12C mutation: A randomised, open-label, phase 3 trial. Lancet 401:733-746, 2023.

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