...higher ORR was linked with KRAS/TP53 mutation, while longer PFS was merely associated with the mutation in TP53 (HR 0.72, 95%CI 0.55-0.95, P=0.019), but not KRAS (P=0.295). TP53 mutation brought improvement of ORR and PFS in patients with KRAS mutation (ORR, p=0.002; PFS, p<0.001), but not KRAS-WT population (ORR, p=0.104; PFS, p=0.566). KRAS mutation was associated with better ORR and PFS in TP53-mut (ORR, p=0.011; PFS, p=0.017), but not TP53-WT population (ORR, p=0.518; PFS, p=0.885). We further investigated the predictive efficacy of the co-mutation of TP53 and KRAS, and observed remarkably improved ORR (2.59-fold, P<0.001) and PFS (HR 0.47, 95%CI 0.32-0.68, P=0.001) in co-mutated patients. Co-mutation of KRAS and TP53 is identified as a potential immunotherapeutic predictor of better ORR and PFS in patients with EGFR/ALK WT non-squamous NSCLC.

Of these, 17 patients had a major pathological response, which was significantly higher than in the non-KRAS driver mutation group (60.7% vs. 31.6%, P = 0.049)….Our study suggests that NSCLC patients with KRAS driver mutations have a superior response to neoadjuvant immunotherapy...

69 patients received chemo or chemo/IO for resectable KRAS-mutated NSCLC….MPR was observed in 15 (22%) pts with 3 cases of pCR….Median EFS in all pts was 1.7 years (95% CI: 1.1-3.5). EFS was significantly longer in pts with MPR (p=0.002)….Our analysis demonstrated neoadjuvant chemo/IO was associated with higher MPR in KRAS-mutated NSCLC pts than chemo alone. Achieving MPR prolonged EFS and OS.

We compared the progression-free survival (PFS) of 324 advanced NSCLC patients who received ICI monotherapy (as over second-line therapy) by different AGAs....A total of 324 patients were included with the following AGAs: EGFR mutation (n = 149, 46.0%), ALK rearrangement, (n = 12, 3.7%), KRAS mutation (n = 72, 22.2%), HER2 mutation or amplification (n = 34, 10.5%), and MET ex14 skipping or amplification (n = 32, 9.9%), ROS1 rearrangement (n = 9, 2.8%), BRAF V600E (n = 9, 2.8%), and RET rearrangement (n = 7, 2.2%).....The 6-month PFS rate was 25.8% (19.5–34.3) in the group with KRAS/BRAF V600E/MET/HER2 and 12.8% (8.6–19.1) in the group with EGFR/ALK/ROS1/RET (P < 0.01)...the KRAS/BRAF V600E/MET/HER2 group had a favorable PFS compared with the EGFR/ALK/ROS1/RET group.

NSCLC patients with KRAS and/or TP53 mutations treated with ICIs showed significantly higher objective response rate, disease control rate, PFS, and OS compared to NSCLC patients with wild-type KRAS/TP53 (P < 0.05).

...KRAS patients could benefit from first-line immunotherapy (10.1 months, P < 0.05), patients with EGFR mutations have poor first-line immunotherapy outcomes, with a median PFS of only 3.0 months (P < 0.01)…

The study included 95 patients with KRAS-mutant advanced NSCLC. Patients treated with first-line ICIs plus platinum-containing chemotherapy had better progression-free survival (PFS) (7.4 vs 4.5 months, P = 0.035) and overall survival (OS) (24.1 vs 13.2 months, P = 0.007) than those receiving platinum-containing chemotherapy alone, and second-line ICI monotherapy was associated with better PFS (4.8 vs 3.0 months, P = 0.043) and OS (18.0 vs 13.8 months, P = 0.013) than chemotherapy monotherapy...patients with advanced NSCLC with KRAS mutations can benefit from ICIs, but no difference between KRAS mutant subtypes was observed.

Patients with advanced NSCLC without driver alterations who were treated with ICI and platinum-based chemotherapy (N=80) were identified....The OS and PFS of patients with KRAS mutations were significantly higher than those in the non-KRAS mutant group (P<0.05)....This work provides evidence that KRAS mutation in advanced NSCLC may be served as a potential predictive biomarker for immunotherapeutic efficacy.

We found that among patients received immunotherapy, KRAS-mutant patients were more sensitive to immunotherapy, with an objective response rate (ORR) of 65% and a disease control rate (DCR) of 80%.

We assessed the association of clinical or molecular factors with the efficacy of ICI given either alone (ICI alone) or combined with other treatments (ICI-based combination treatments)….ICI had significantly lower efficacy in EGFR-mutated NSCLC while KRAS-mutated NSCLC showed higher efficacy.

We conducted this retrospective cohort study on patients with NSCLC harboring oncogenic driver alterations and treated with an immune checkpoint inhibitor combined with chemotherapy....In patients with KRAS mutations (n = 10) or PD-L1 expression of 50% or greater (n = 10), the disease control rate was 100%.

This retrospective, pooled analysis suggests that patients with KRAS-mutated NSCLC benefit from 1L chemo-ICI similarly to those with KRAS wild-type NSCLC, and should receive combination therapy upfront. Patients with KRAS-mutated NSCLC derived the greatest benefit from the combination of chemo-ICI as compared to ICI or chemo alone.

Patients with KRAS mutations showed the greatest survival benefit from Immune checkpoint inhibitors (ICIs) with the PFS of 9.7 (4.8-14.6) months and OS of 31.2 (19.4-50.6) months. They mostly received the first-line (34.6%, 18/52) and second-line (38.5%, 20/52) ICIs....KRAS mutant NSCLC patients mostly receive ICIs at the front line, and have best survival benefits from immunotherapy.

We conducted a retrospective case-control study using information abstracted from a Johns Hopkins IRB-approved database of NSCLC patients treated with an ICI-containing regimen. We defined long-term responders (LR) as patients who have achieved an overall survival (OS) of at least 3 years....KRAS mutation was assessed in 34 patients (LR=16, C=18) and was associated with LR status versus C (Fisher’s exact test value p=0.0386).

In our cohort, patients with KRAS mutations were found to have better OS (26.94 vs. 12.02 months, HR 0.63, 95% CI 0.42-0.93, p=0.02) and PFS (6.76 vs. 3.84 months, HR 0.68, 95% CI 0.47-0.98, p=0.04) compared with patients without KRAS mutations….KRAS mutations are associated with prolonged survival in patients with NSCLC treated with ICI monotherapy, with no differences according to mutation subtypes.

Most of the patients (21/24) received induction immunotherapy plus chemotherapy...For KRAS mutations, MPR rate was 50.0% (3/6) and pCR rate was 16.7% (1/6).

However, in patients with a KRAS mutation, ICI-90 led to a one-year survival of 60.4% vs 34.1% (p = 0.004). Patients with NSCLCBM who received ICI-90 had improved OS compared to no-ICI patients....Finally, our data suggests the greatest benefit of ICIs are seen in patients with KRAS mutations in their tumors, which should be considered in future trials.

We conducted a retrospective study including all consenting patients with NSCLC treated with ICIs...When the presence of a KRAS mutation was compounded with STK11 and KEAP1, KRASMut (vs KRASWT) trended to a better prognosis in STK11+KEAP1WT tumors (median OS of 21.1 for KRASMut vs 15.8 for KRASWT, p = 0.15), but not in STK11+/-KEAP1Mut tumors (7.4 for KRASMut vs 7.0 for KRASWT)....In STK11-KEAP1WT tumors, KRAS mutations seems to be associated with improved survival in NSCLC patient treated with ICIs.

...we conducted a systematic review and meta-analysis to compare efficacy of immune checkpoint inhibitors for NSCLC patients with different genes mutation….Meanwhile, they prolonged the OS (HR, 0.61; 95% CI, 0.39-0.94) in NSCLC patients with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation.

CONTRADICTING EVIDENCE: KRAS-mutated patients did not seem to benefit more from ICI than chemotherapy.

CONTRADICTING EVIDENCE: mPFS in patients harboring KRAS mutations was 4.9 m ( vs 10.1 m in patients without KRASmut, logrank test p-value = 0.031) and 4.1 m in those patients with STK11 mutations (vs 9.5 m in patients without STK11mut, logrank test p-value = 0.034). Additionally, mutations in both genes were also associated to statistically significant shorter mPFS 3.9 m vs 9.5 m (logrank test p-value < 0.01).

ICI has inconstant efficacy in NSCLC harboring activating mutation. KRAS, BRAF and MET-exon 14 patients derive a greater benefit than EGFR, ALK and RET patients