Abstract
Introduction
With the approval of G12C inhibitors as the second line of treatment for KRAS G12C-mutated NSCLC, and the expanding research regarding targeting KRAS, it is key to understand the prognostic implication of KRAS G12C in the current first line of treatment. We compared overall survival (OS) of patients with stage IV KRAS G12C-mutated NSCLC to those with a KRAS non-G12C mutation in a first-line setting of (chemo)immunotherapy.
Methods
This nationwide population-based study used real-world data from The Netherlands Cancer Registry. We selected patients with stage IV KRAS-mutated lung adenocarcinoma diagnosed in 2019 to 2020 who received first-line (chemo-)immunotherapy. Primary outcome was OS.
Results
From 28,120 registered patients with lung cancer, 1185 were selected with a KRAS mutation, of which 494 had a KRAS G12C mutation. Median OS was 15.5 months (95% confidence interval [CI]: 13.6–18.4) for KRAS G12C versus 14.0 months (95% CI:11.2–15.7) for KRAS non-G12C (p = 0.67). In multivariable analysis, KRAS subtype was not associated with OS (hazard ratio = 0.95, 95% CI: 0.82–1.10). For the subgroup with programmed death-ligand 1 at 0% to 49% who received chemoimmunotherapy, median OS was 13.3 months (95% CI: 10.5–15.2) for G12C and 9.8 months (95% CI: 8.6–11.3) for non-G12C (p = 0.48). For the subgroup with programmed death-ligand 1 more than or equal to 50% who received monoimmunotherapy, the median OS was 22.0 months (95% CI: 18.4–27.3) for G12C and 18.9 months (95% CI: 14.9–25.2) for non-G12C (p = 0.36).
Conclusions
There was no influence of KRAS subtype (G12C versus non-G12C) on OS in patients with KRAS-mutated stage IV NSCLC treated with first-line (chemo)immunotherapy.
Keywords: Non–small cell lung cancer, Kirsten rat sarcoma, KRAS G12C, (Chemo-)immunotherapy
Introduction
KRAS is the most common driver mutation in patients with NSCLC, occurring in 30% to 40% of all NSCLC adenocarcinomas in western populations.1, 2, 3, 4 Through downstream signaling, mutations in KRAS can lead to uncontrolled cell growth and proliferation.1,5,6
Of all KRAS mutations, the KRAS G12C mutation is found in approximately 40% to 45% of all patients with KRAS-mutated NSCLC.2,7, 8, 9, 10
In the past, KRAS was considered to be “undruggable,” as several attempts to target this driver mutation were unsuccessful.6,11, 12, 13, 14 Recently, small molecules such as sotorasib and adagrasib were successfully able to keep the KRAS G12C molecule in its inactive state preventing downstream signaling.15, 16, 17 In clinical phase 2 studies, sotorasib and adagrasib were found to have an overall response rate (ORR) of 41% and 42.9% and a median progression-free survival (PFS) of 6.3 and 6.5 months, respectively, in patients with progressive disease after at least one previous line of systemic therapy.18,19 In the subsequent CodeBreaK 200 phase 3 trial, sotorasib had a superior median PFS than docetaxel (5.6 mo for sotorasib versus 4.5 mo for docetaxel, hazard ratio [HR] = 0.66, p = 0.0017). The PFS rate at 12 months was 24.8% for sotorasib and 10.1% for docetaxel.20,21 Covalent inhibitors of KRAS G12C have now become available as a second line of therapy for KRAS G12C-mutated NSCLC.22,23
Considering the new benchmark for KRAS G12C in this second line and the expanding research efforts to move KRAS inhibitors to the first line, it is key to understand the prognostic implication of KRAS G12C in the current first-line setting of treatment with immune checkpoint inhibitors or combination chemoimmunotherapy according to the tumor programmed death-ligand 1 (PD-L1) status. The prognostic role of KRAS G12C is currently unknown, as large real-world series regarding outcomes of patients with KRAS G12C-mutated NSCLC treated with (chemo)immunotherapy in a first-line setting are lacking. Only for unspecified KRAS mutations it has been found that there was no prognostic value of the KRAS mutational status in patients with stage IV NSCLC treated with first-line pembrolizumab.24 Nevertheless, regarding the prognostic role of KRAS G12C, current available literature is inconclusive as these studies were performed in small, selected populations.9,25, 26, 27, 28, 29, 30, 31, 32, 33, 34
To assess this real-world prognostic implication of KRAS G12C in relation with other KRAS subtypes, a large cohort study is needed, preferably in a real-world population. Using a population-based study in a nationwide cohort with real-world data, we aim to describe overall survival (OS) and to evaluate the prognostic implication of KRAS G12C for treatment with first-line monoimmunotherapy and combination immuno-chemotherapy in patients with lung adenocarcinoma compared with those with a KRAS non-G12C mutation.
Materials and Methods
Study Design
In this nationwide population-based study, real-world data from The Netherlands Cancer Registry (NCR) were used. The NCR is a population-based cancer registry that contains data of all individuals newly diagnosed with cancer in The Netherlands.35,36 Trained registration employees routinely collect data on patient and tumor characteristics (e.g., TNM classification of malignant tumors edition 8, WHO performance score [PS]), diagnostics, and treatments prescribed in the first line. For NSCLC, PD-L1 tumor proportion score and driver mutations are also reported. From patients diagnosed from 2019, information on KRAS subtype (G12C versus non-G12C) was collected. This retrospective, noninterventional study did not require approval from an accredited medical ethics committee or the Central Committee on Research involving Human Subjects. The study, however, has been reviewed and approved by the NCR’s Supervisory Committee and the multidisciplinary scientific committee regarding lung cancer (application number K22.135).
Study Population
From the NCR, we selected all adult patients (aged ≥18 y) newly diagnosed with stage IV (as defined by clinical TNM IVA–B, TNM classification of malignant tumors eighth edition) KRAS-mutated NSCLC between January 1, 2019, and December 31, 2020. In addition, we restricted the cohort to patients diagnosed with the adenocarcinoma subtype and patients who received first-line treatment with immunotherapy with or without chemotherapy within 90 days of stage IV diagnosis. We excluded patients who tested also positive for other molecular driver alterations. Patients with an unknown PD-L1 expression level were also excluded.
Statistical Analyses
Summary statistics were used to describe patient demographics, clinical characteristics, and tumor characteristics. OS was calculated from the start date of first-line systemic treatment to date of death from any cause. Patients without evidence of death were censored on February 1, 2022. The primary end point of this study was OS in which patients with KRAS G12C were compared with patients with KRAS non-G12C. OS was presented as 1-year and 2-year OS, and median survival time with corresponding 95% confidence intervals (CIs) using Kaplan-Meier curves. Log-rank tests were used to test for significant differences between the subgroups. Cox proportional hazards regression was used to assess HRs and 95% CIs in multivariable analysis including age, sex, WHO PS, number of organs with metastases, PD-L1 expression, year of diagnosis, and KRAS status. PD-L1 expression was included in potentially biological relevant cutoffs; therefore, next to the common cutoff values of 0% and 1% to 49%, we applied 50% to 89% and more than or equal to 90%. KRAS status was maintained in the final model, irrespective of prognostic significance. Other independent prognostic factors were determined using the backward selection method, where a p value of less than 0.05 was considered significant. Treatment type was not included in the multivariable model owing to collinearity with PD-L1. All analyses were performed using SAS, version 9.4 (SAS Institute, Cary, NC).
Results
The NCR included a total of 28,120 patients with lung cancer in the study period, of whom a total of 1185 patients were selected (Fig. 1) with stage IV KRAS-positive adenocarcinoma of the lung, being treated with first-line immunotherapy or combination chemoimmunotherapy. Patient characteristics are outlined in Table 1. Of these patients, 494 had KRAS G12C-mutated NSCLC (41.7%), and the other 691 (58.3%) had non-G12C KRAS-mutated NSCLC. Of all included patients, 55.5% were female. Most of the patients had a WHO PS of 0 or 1 (81.2%).
Figure 1.
Flowchart patient selection. PD-L1, programmed death-ligand 1.
Table 1.
Patient Characteristics
| Overall (N = 1185), |
KRAS G12C (n = 494), |
KRAS Non-G12c (n = 691), |
|
|---|---|---|---|
| Characteristic | n (%) | n (%) | n (%) |
| Age | |||
| 18–59 | 317 (26.8) | 128 (25.9) | 189 (27.4) |
| 60–69 | 477 (40.3) | 206 (41.7) | 271 (39.2) |
| ≥70 | 391 (33.0) | 160 (32.4) | 231 (33.4) |
| Sex | |||
| Men | 527 (44.5) | 216 (43.7) | 311 (45.0) |
| Women | 658 (55.5) | 278 (56.3) | 380 (55.0) |
| WHO performance score | |||
| 0 | 444 (37.5) | 195 (39.5) | 249 (36.0) |
| 1 | 518 (43.7) | 207 (41.9) | 311 (45.0) |
| ≥2 | 99 (8.4) | 42 (8.5) | 57 (8.2) |
| Unknown | 124 (10.5) | 50 (10.1) | 74 (10.7) |
| Number of metastatic organs | |||
| 1 | 501 (42.3) | 202 (40.9) | 299 (43.3) |
| 2 | 341 (28.8) | 145 (29.4) | 196 (28.4) |
| ≥3 | 343 (28.9) | 147 (29.8) | 196 (28.4) |
| PD-L1 | |||
| 0% | 317 (26.8) | 132 (26.7) | 185 (26.8) |
| 1%–49% | 292 (24.6) | 121 (24.5) | 171 (24.7) |
| 50%–89% | 378 (31.9) | 158 (32.0) | 220 (31.8) |
| ≥90% | 198 (16.7) | 83 (16.8) | 115 (16.6) |
| Year | |||
| 2019 | 572 (48.3) | 224 (45.3) | 348 (50.4) |
| 2020 | 613 (51.7) | 270 (54.7) | 343 (49.6) |
| Treatment | |||
| Chemoimmunotherapy | 735 (62.0) | 302 (61.1) | 433 (62.7) |
| Monoimmunotherapy | 450 (38.0) | 192 (38.9) | 258 (37.3) |
PD-L1, programmed death-ligand 1.
The percentage of patients with KRAS G12C was slightly lower in 2019 compared with 2020. Distinction between the KRAS subtypes was introduced at the NCR in 2019, and some miscoding may have taken place. Nevertheless, similar results were obtained in sensitivity analyses stratifying for period of diagnosis.
Of all patients, 62% were treated with chemoimmunotherapy and 38% with monoimmunotherapy. In addition, of all patients with a PD-L1 expression more than or equal to 50%, 77% received monoimmunotherapy and the other 23% combination chemoimmunotherapy. From all patients with a tumor PD-L1 expression less than 50%, 99% received combination chemoimmunotherapy (Supplementary Table A.1). Monoimmunotherapy comprised pembrolizumab in all the patients.
The median OS, regardless of treatment type, of the patients with a KRAS G12C NSCLC was 15.5 months (95% CI: 13.6–18.4) versus 14.0 months (95% CI: 11.2–15.7) for KRAS non-G12C (p = 0.67; Fig. 2). In univariable analysis, sex was a significant prognostic factor for OS, as women had a superior survival compared with men (p < 0.0001). Associated with poorer survival were poorer WHO PS (p < 0.0001), higher number of metastatic organs (p < 0.0001), and lower PD-L1 expression (p < 0.0001). Type of treatment was also a significant prognostic factor for survival, as monoimmunotherapy was associated with a higher survival (p < 0.0001; Table 2).
Figure 2.
Kaplan-Meier overall survival KRAS non-G12C versus KRAS G12C.
Table 2.
Univariable Analysis of Overall Survival
| Variable | n | 1-y, % | 95% CI | 2-y, % | 95% CI | p Value |
|---|---|---|---|---|---|---|
| Age | ||||||
| 18–59 | 317 | 58 | (53–64) | 42 | (36–48) | 0.0044 |
| 60–69 | 477 | 57 | (52–61) | 37 | (32–42) | |
| ≥70 | 391 | 49 | (44–54) | 32 | (27–37) | |
| Sex | ||||||
| Men | 527 | 49 | (44–53) | 31 | (27–35) | <0.0001 |
| Women | 658 | 60 | (56–63) | 42 | (37–46) | |
| WHO performance score | ||||||
| 0 | 444 | 65 | (61–70) | 46 | (41–51) | <0.0001 |
| 1 | 518 | 50 | (46–54) | 32 | (28–37) | |
| ≥2 | 99 | 39 | (30–49) | 32 | (23–42) | |
| Unknown | 124 | 48 | (39–56) | 25 | (16–34) | |
| Number of metastatic organs | ||||||
| 1 | 501 | 64 | (59–68) | 46 | (41–51) | <0.0001 |
| 2 | 341 | 55 | (50–60) | 35 | (29–41) | |
| ≥3 | 343 | 41 | (36–46) | 25 | (21–31) | |
| PD-L1 | ||||||
| 0% | 317 | 41 | (36–46) | 20 | (16–26) | <0.0001 |
| 1%–49% | 292 | 55 | (49–61) | 35 | (29–41) | |
| 50%–89% | 378 | 59 | (54–64) | 45 | (39–50) | |
| ≥90% | 198 | 67 | (60–73) | 50 | (42–58) | |
| Year | ||||||
| 2019 | 572 | 57 | (52–61) | 38 | (34–42) | 0.3329 |
| 2020 | 613 | 53 | (49–57) | - | (-) | |
| KRAS | ||||||
| KRAS G12C | 494 | 57 | (53–62) | 35 | (30–40) | 0.6683 |
| KRAS non-G12C | 691 | 53 | (49–56) | 38 | (34–42) | |
| Treatment | ||||||
| Chemoimmunotherapy | 735 | 50 | (47–54) | 31 | (28–35) | <0.0001 |
| Monoimmunotherapy | 450 | 62 | (57–66) | 46 | (41–51) | |
CI, confidence interval; PD-L1, programmed death-ligand 1.
Sex, WHO PS, number of metastatic organs, and PD-L1 status remained significant prognostic factors in multivariable analysis (Table 3). KRAS mutation status (i.e., G12C versus non-G12C) was in this multivariable analysis not significantly associated with OS (HR = 0.95, 95% CI: 0.82–1.10).
Table 3.
Multivariable Analysis of Overall Survival
| Variable | Hazard Ratio | 95% CI |
|---|---|---|
| Age | ||
| 18–59 | 1 | |
| 60–69 | 1.17 | (0.97–1.41) |
| ≥70 | 1.39 | (1.14–1.70) |
| Sex | ||
| Men | 1 | |
| Women | 0.83 | (0.71–0.96) |
| WHO performance score | ||
| 0 | 1 | |
| 1 | 1.44 | (1.22–1.71) |
| ≥2 | 1.85 | (1.41–2.44) |
| Unknown | 1.75 | (1.36–2.25) |
| Number of metastatic organs | ||
| 1 | 1 | |
| 2 | 1.30 | (1.08–1.56) |
| ≥3 | 2.02 | (1.70–2.41) |
| PD-L1 | ||
| 0% | 1 | |
| 1%–49% | 0.63 | (0.51–0.76) |
| 50%–89% | 0.53 | (0.44–0.64) |
| ≥90% | 0.38 | (0.30–0.49) |
| Year | ||
| 2019 | - | |
| 2020 | ||
| KRAS | ||
| KRAS non-G12C | 1 | |
| KRAS G12C | 0.95 | (0.82–1.10) |
CI, confidence interval; PD-L1, programmed death-ligand 1.
For the subgroup with PD-L1 at 0% to 49% who received combination chemoimmunotherapy, median OS was 13.3 months (95% CI: 10.5–15.2) for G12C and 9.8 months (95% CI: 8.6–11.3) for non-G12C (p = 0.48; Supplementary Fig. A.1A). No differences were observed in the subgroup with a tumor PD-L1 expression of 0% (median OS for G12C at 10.0 mo [95% CI: 6.6–13.3] versus median OS for non-G12C at 8.8 mo [95% CI: 6.8–9.8]; p = 0.80; Supplementary Fig. A.1B) and in the subgroup with PD-L1 at 1% to 49% (median OS for G12C at 16.0 mo [95% CI: 13.1–21.3] versus median OS for non-G12C at 12.2 mo [95% CI: 10.0–19.4], p = 0.43; Supplementary Fig. A.1C).
Different treatment strategies were used in patients with a PD-L1 expression more than or equal to 50% (Supplementary Table A.1). The median OS of patients with a PD-L1 expression more than or equal to 50% who were treated with monoimmunotherapy was 22.0 months (95% CI: 18.4–27.3) for G12C and 18.9 months (95% CI: 14.9–25.2) for non-G12C (p = 0.36; Supplementary Fig. A.2). Patients with a PD-L1 expression more than or equal to 50% who received combination chemoimmunotherapy had a median OS of 13.2 months (95% CI: 6.9–not evaluable) for those with KRAS G12C-mutated NSCLC and 30.5 months (95% CI:14.0–not evaluable) for those with KRAS non–G12C-mutated NSCLC (Fig. 3).
Figure 3.
Kaplan-Meier subgroup with PD-L1 more than or equal to 50% by treatment for KRAS non-G12C versus KRAS G12C. PD-L1, programmed death-ligand 1.
We observed no significant difference in OS between the two treatment strategies for patients with PD-L1 expression more than or equal to 50% in regard to treatment type (monoimmunotherapy or combination chemoimmunotherapy) and KRAS mutational status (KRAS G12C or KRAS non-G12C) (p = 0.32; Fig. 3).
Discussion
In this nationwide population-based study using real-world data, the OS of patients with stage IV NSCLC with a KRAS G12C versus a non-G12C mutation was similar, when treated with first-line monoimmunotherapy or combination chemoimmunotherapy. Unspecified KRAS mutational status was already known to have no prognostic impact on OS in patients with stage IV lung adenocarcinoma.24,34 This study established that the G12C subtype neither influences survival.
In the KEYNOTE-042 study, patients with KRAS G12C-positive NSCLC had similar ORR, PFS, and OS compared with the overall cohort of patients with unspecified KRAS-mutated NSCLC while being treated with pembrolizumab monotherapy.37,38 In the KEYNOTE-189, it was found that patients with KRAS G12C-positive NSCLC had similar ORR compared with all patients with unspecified KRAS-mutated NSCLC after treatment with pembrolizumab plus chemotherapy.39,40 Nevertheless, these were post hoc analyses with a relatively small number of patients.
Justeau et al.34 found in a smaller and more selected KRAS-positive stage IV NSCLC cohort (with only PD-L1 ≥50%, treated with first-line immunotherapy) an OS of 18.4 months versus 20.6 months for KRAS G12C (n = 86) versus non-G12C (n = 141), respectively. These results are similar to the OS reported in the current study. Other previous studies lacked conclusive evidence regarding the real-world prognostic value of KRAS G12C, mainly owing to limited sample sizes, and these studies were rarely performed in a first-line setting.9,25,27, 28, 29, 30, 31
In our cohort, 55.5% of all patients with a KRAS mutation were female. This contrasts with two large cohorts from France and Germany10,41 but corresponds with other studies.2,8,9,42 In our study, sex was a significant prognostic factor for OS, as women had a better survival than men which was not explained by differences in patient and tumor characteristics (p < 0.0001). This was not found in other larger KRAS cohorts, but in these cohorts, patients with stages I to IV NSCLC with different treatment modalities were included,42,43 and our study included only those with stage IV treated with systemic therapy. This could mean that there are sex-specific influences in patients with stage IV NSCLC with a KRAS mutation.
Strengths of this study are that it is a nationwide population-based study using real-world data and, to our knowledge, the largest cohort to evaluate the prognostic implication of KRAS G12C in the setting of first-line (chemo)immunotherapy.
As this study used NCR data, no data were available regarding PFS, compliance to treatment, comorbidity, or cause of death. In addition, data containing co-mutations were not included in the data set. KRAS can have co-occurring mutations in TP53, STK11, and KEAP1, with a prevalence of 39% to 48%, 12% to 30%, and 8% to 27%, respectively.9,43, 44, 45, 46 In a large study, the frequencies of TP53, STK11, and KEAP1 were similar in KRAS G12C and non–G12C-mutated lung cancer.9 In literature, patients with a KRAS G12C and co-occurring STK11 mutation had a significant shorter time to next treatment and shorter OS with immunotherapy or combination chemoimmunotherapy than patients without the co-occurring STK11 mutation.47 Patients with KRAS and co-occurring KEAP1 mutation had a shorter OS with platinum-based chemotherapy and immunotherapy.44,48 In the sotorasib phase 2 study, patients with KRAS G12C-mutated NSCLC who had STK11 wild type but had a KEAP1 alteration seemed to have the lowest response rate, although this was not sufficiently powered for statistical analysis.18 A similar effect was found with adagrasib, suggesting that this KEAP1 co-occurring mutation has an impact on treatment response.19
In this real-world study, 77% of the patients with a PD-L1 expression of more than or equal to 50% were treated with monoimmunotherapy. The other 23% was treated with combination chemoimmunotherapy and could possibly reflect a population with a higher tumor burden and more rapid progressive disease. To prevent bias due to this, separate survival analysis was performed in the subgroup with PD-L1 more than or equal to 50%, for those treated with monoimmunotherapy and those with combination chemoimmunotherapy.
Furthermore, it is important to notice that this study was performed in a predominantly white population. In western populations, KRAS mutations are more frequently reported than in populations from Asian descent.49 The G12C mutation is observed more often in white and black women than in white and black men, but more often in Asian men than in Asian women.50
A subject for future research is whether co-occurring alterations with KRAS G12C have a predictive role on survival. Furthermore, one could hypothesize if there is a subgroup that could possibly benefit from G12C inhibitors instead of (chemo-)immunotherapy or in combination strategies in the first line of therapy. Further research should therefore focus on these topics, now that G12C inhibitors have become available in the therapeutic landscape. Although we did not find survival differences between KRAS non-G12C and KRAS G12C within the 2-year follow-up period, survival differences might emerge over time, because a considerable number of patients were still alive at the end of the follow-up. The relatively lower OS observed in the subgroup with PD-L1 at 0% to 49% who received combination chemoimmunotherapy highlights the need for further research on how to optimize treatment strategies for this subgroup.
In conclusion, we established that the KRAS G12C mutational status was not associated with OS in the first-line setting of patients with stage IV KRAS-mutated NSCLC treated with (chemo-)immunotherapy. For now, PD-L1 status is the most important prognostic biomarker currently available for KRAS-mutant NSCLC. Furthermore, no survival differences were found for the different treatment strategies (monoimmunotherapy versus combination chemoimmunotherapy) used in the subgroup with PD-L1 more than or equal to 50%.
CRediT Authorship Contribution Statement
Anneloes L. Noordhof: Conceptualization, Writing—original draft, Visualization, Project administration.
Esther M. Swart: Conceptualization, Methodology, Formal analysis, Writing—review and editing.
Ronald A. M. Damhuis: Methodology, Writing—review and editing.
Lizza E. L. Hendriks: Writing—review and editing.
Peter W. A. Kunst: Writing—review and editing.
Mieke J. Aarts: Conceptualization, Methodology, Formal analysis, Writing—review and editing, Supervision.
Wouter H. van Geffen: Conceptualization, Methodology, Writing—review and editing, Supervision.
Footnotes
Disclosure: Dr. Swart reports receiving funding from Amgen, outside the submitted work. Funding for additional data collection was paid to the institution. Dr. Hendriks has received grants or contracts from Roche Genentech, AstraZeneca, Boehringer Ingelheim, Takeda, Merck, Pfizer, and Novartis (under negotiation) (paid to the institution) outside of the submitted work; speaker’s fee from Merck Sharp & Dohme and Eli Lilly (paid to the institution); fees for educational webinars from Benecke, Medtalks, VJOncology (self), and high5oncology (paid to the institution) outside of the submitted work; support for attending meetings from Roche Genentech; advisory boards from Bristol-Myers Squibb, Eli Lilly, Roche Genentech, Pfizer, Takeda, Merck Sharp & Dohme, Merck, Novartis, Boehringer Ingelheim, Amgen, and Janssen (except Roche, all paid to the institution) outside of the submitted work; mentorship program funded by AstraZeneca and interview sessions funded by Roche Genentech, Bayer, and Eli Lilly (all paid to the institution) outside of the submitted work; served as a local principal investigator of clinical trials for AstraZeneca, Novartis, Bristol-Myers Squibb, Merck Sharp & Dohme, Merck, GlaxoSmithKline, Takeda, Blueprint Medicines, Roche Genentech, Janssen Pharmaceuticals, Mirati, AbbVie, and Gilead. Dr. Aarts reports receiving funding from Amgen that was paid to the institution, outside the submitted work. Dr. van Geffen has unpaid roles for ERS and NVALT outside of the submitted work; and there have been trials run by his department funded by Roche, Merck Sharp & Dohme, and Amgen. The remaining authors declare no conflict of interest.
Cite this article as: Noordhof AL, Swart EM, Damhuis RAM, et al. Prognostic implication of KRAS G12C mutation in a real-world KRAS-mutated stage IV NSCLC cohort treated with immunotherapy in The Netherlands. JTO Clin Res Rep. 2023;4:100543.
Note: To access the supplementary material accompanying this article, visit the online version of the JTO Clinical and Research Reports at www.jtocrr.org and at 10.1016/j.jtocrr.2023.100543.
Supplementary Data
References
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