Updated CodeBreak 200 analyses boost sotorasib role in KRASG12C-mutant NSCLC

Audrey Abella
19 Jun 2023
Updated CodeBreak 200 analyses boost sotorasib role in KRASG12C-mutant NSCLC

In the PRO analyses of the phase III CodeBreak 200 trial, the first-in-class KRASG12C inhibitor sotorasib improved quality of life (QoL) of patients with pretreated KRASG12C-mutated advanced non-small-cell lung cancer (NSCLC) compared with docetaxel.

“Patients treated with sotorasib vs docetaxel were less bothered by their side effects, experienced less symptom severity, and less interference in daily activities,” said Dr David Waterhouse from Dana Farber Cancer Center, Boston, Massachusetts, US, at ELCC 2023. “They also had significantly improved mobility, self-care, and ability to perform usual activities.”

In the Forrest plot looking at different domains that could affect QoL, sotorasib recipients appeared to fare better over time. At week 12, sotorasib side effects were less bothersome than those reported with docetaxel (odds ratio [OR], 5.71; p<0.001).

Patients also favoured sotorasib over docetaxel in terms of severity of pain (OR, 2.94; p=0.014), aching muscles (OR, 4.40; p=0.005), aching joints (OR, 4.17; p=0.009), and mouth or throat sores (OR, 4.26; p=0.004). [ELCC 2023, abstract 4O]

Symptoms of pain (OR, 3.18; p=0.018), aching muscles (OR, 3.90; p=0.033), and aching joints (OR, 10.68; p<0.001) interfered less with the performance of usual/daily activities in sotorasib recipients compared with those on docetaxel.

“From these data, the message is somewhat consistent that there seemed to be a favouring of sotorasib over docetaxel,” said Waterhouse.


Treatment impact on QoL, health status

QoL worsened with docetaxel, whereas with sotorasib, it remained stable, noted Waterhouse. These were reflected in the changes in Visual Analogue Scale scores from baseline, both during day 5 of cycle 1 (+1.5 [sotorasib] vs –8.4 [docetaxel]) and day 1 of cycle 5 (+2.2 vs –5.8).

Compared with docetaxel, sotorasib was associated with improvements in mobility (OR, 2.76), self-care (OR, 2.93), usual activities (OR, 1.93), and pain/discomfort (OR, 1.62).


PROs: Critical assessment tools

A total of 345 participants (median age 64 years, 59 percent male) were randomized 1:1 to receive oral sotorasib 960 mg daily or IV docetaxel 75 mg/m2 Q3W. Patients completed multiple* PRO questionnaires to capture their perceptions of QoL and symptom burden.

“Being patient-centric is important … The impact of a symptom needs to be reported by patients,” underscored Waterhouse, noting that symptoms such as pain cannot be accurately assessed by the investigator.

Discussant Professor Jarushka Naidoo from the Beaumont RCSI Cancer Centre, Dublin, Ireland, couldn’t have agreed more. “[PROs] may have more accurate associations with their experience compared with clinician-only reporting. PROs play a critical role in the evaluation of certain treatments … Therefore, our ability to accurately depict symptom burden and QoL of patients is increasingly important and has implications for drug approval,” she said.

Professor Massimo Di Maio from the University of Turin, Italy, echoed similar sentiments in a press release. “QoL is a really important endpoint in the setting of patients receiving second-line treatment for lung cancer, who have limited life expectancy and whose overall condition after the failure of first-line treatment can be quite poor … PROs are particularly important in helping to determine the value of one treatment over another.”


A more tolerable treatment option

The trial met its primary endpoint of improved progression-free survival, and this was supported by other secondary endpoints such as objective response rate, disease control rate, time to response, and duration of response. [Lancet 2023;401:733-746]

“[The current results show that] sotorasib improved QoL compared with docetaxel, suggesting that sotorasib may be a more tolerable treatment option for patients with previously treated NSCLC who have the KRASG12C mutation,” said Waterhouse.

“[These data show that] docetaxel with or without antiangiogenic therapy is a current and fair comparator but a low bar when it comes to QoL. Patients were indeed living better as a result of sotorasib [treatment]. CodeBreak 200 has established sotorasib as a standard therapy for KRASG12C NSCLC,” Naidoo said.


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