Efficacy of immunotherapy in KRAS-mutant non-small-cell lung cancer with comutations

Immunotherapy ◽  
2021 ◽  
Author(s):  
Alexander P Davis ◽  
Wendy A Cooper ◽  
Michael Boyer ◽  
Jenny H Lee ◽  
Nick Pavlakis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Single Agent ◽  
Small Cell ◽  
Significant Heterogeneity ◽  
Small Cell Lung ◽  
Kras Mutations ◽  
First Line Therapy ◽  
Improved Outcomes

KRAS-mutant non-small-cell lung cancer is the most common molecular driver of lung adenocarcinoma in western populations. No  KRAS specific therapy has been approved by the FDA until 2021. Despite significant heterogeneity in comutations, patients typically receive single-agent immunotherapy or chemoimmunotherapy as standard first-line therapy. It is unclear whether KRAS mutations predict outcomes with immunotherapy; however, there is emerging data suggesting improved outcomes in patients with a  TP53 comutation and worse outcomes in patients with a  STK11/LKB1 or  KEAP1 comutation.

scholarly journals P2.01-043 PD-L1 Expression, EGFR and KRAS Mutations in First-Line Therapy (1L) for Non-Small Cell Lung Cancer (NSCLC) Patients

2017 ◽  
Vol 12 (11) ◽  
pp. S2085-S2086 ◽  
Author(s):  
D. Cronin-Fenton ◽  
T. Dalvi ◽  
E. Hedgeman ◽  
M. Norgaard ◽  
L. Petersen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Kras Mutations ◽  
First Line Therapy ◽  
Line Therapy ◽  
Nsclc Patients

Clinical responses and survival in Hispanic patients with non-small cell lung cancer treated with immunotherapy compared with non-Hispanic whites.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18109-e18109
Author(s):  
Luis E. Raez ◽  
Diana Saravia ◽  
Rossana Ruiz ◽  
Daniel Sumarriva ◽  
Teresita Munoz-Antonia ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Single Agent ◽  
Progression Free Survival ◽  
Small Cell ◽  
Second Line ◽  
Small Cell Lung ◽  
First Line ◽  
First Line Therapy

e18109 Background: The main immunotherapy (IMMUNO) trials that led to the approval of these agents for non-small cell lung cancer (NSCLC) accrued a minimum number of Hispanic (HISP) patients (pts) or, in some studies, no HISP pts at all. Additional data is thus needed to validate outcomes in HISP pts with NSCLC treated with IMMUNO. While it is known that genomic profiles and cancer survivals are different between HISP, Non-Hispanic Whites (NHW), and African-Americans; no study has yet looked at differences in IMMUNO outcomes between these populations. Methods: We present data in 436 NSCLC pts treated with IMMUNO at 5 large institutions (3 in the US, 2 in Latin America). The agents evaluated include: nivolumab, pembrolizumab and atezolizumab. 256 pts were HISP and 180 pts were NHW. Most of the pts were treated with single agent therapy as second line (or beyond) while a small group of pts were treated as first line. The primary endpoints of the study were: response rate (ORR), progression free survival (PFS) and overall survival (OS). Results: Among NHW pts, disease control rate (DCR) was 67% for Adenocarcinomas (Adeno) and 46% for squamous cell carcinomas (SQCC). In HISP pts there were no differences in DCR rates between both histologies: 68% for Adeno and 67% SQCC. There were no statistical significant differences among HISP and NHW pts regarding ORR, PFS, OS, and responses according to PD-L1 status. Conclusions: This is the largest publication and comparison of NSCLC immunotherapy outcomes in HISP vs NHW pts. No significant differences were found in the clinical outcomes between these 2 ethnic groups despite expected genomic differences. Pts with actionable mutations were excluded as they usually do not get IMMUNO as first or second line; an approach that might change after IMPOWER 150. These results are comparable to the ones seen in Checkmate and Keynote studies. As expected, higher response rates were seen in first line therapy and pts with PD-L1 (+) status. Further comparisons will be better addressed by a larger prospective study.[Table: see text]

scholarly journals Selective KRAS G12C inhibitors in non-small cell lung cancer: chemistry, concurrent pathway alterations, and clinical outcomes

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Gabriela Palma ◽  
Faisal Khurshid ◽  
Kevin Lu ◽  
Brian Woodward ◽  
Hatim Husain
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Single Agent ◽  
Small Cell ◽  
Small Cell Lung ◽  
Kras Mutations ◽  
Prior Therapy ◽  
Fda Approval ◽  
Us Fda

AbstractCancers harboring mutations in the Kirsten rat sarcoma homolog (KRAS) gene have been associated with poor prognosis and lack of targeted therapies. KRAS mutations occur in approximately one in four patients diagnosed with non-small cell lung cancer (NSCLC) with KRAS G12C mutations harbored at approximately 11–16%. Research into KRAS-driven tumors and analytical chemistry have borne a new class of selective small molecules against the KRAS G12C isoform. Phase II data for sotorasib (AMG510) has demonstrated a 37.1% overall response rate (ORR). Adagrasib (MRTX849) has demonstrated a 45% ORR in an early study. While single agent efficacy has been seen, initial data suggest combination approaches are an opportunity to improve outcomes. Here, we present perspectives on the initial progress in targeting KRAS G12C, examine co-mutations evident in KRAS G12C NSCLC, and comment on potential future combinatorial approaches including SHP2, SOS1, MEK, EGFR, mTOR, CDK, and checkpoint blockade which are currently being evaluated in clinical trials. As of May 28, 2021, sotorasib has achieved US FDA approval for patients with KRAS G12C mutant lung cancer after one line of a prior therapy.

scholarly journals Sequencing Therapy for Patients With Lung Cancer

2020 ◽  
Vol 18 (7.5) ◽  
pp. 945-948
Author(s):  
Gregory J. Riely
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Single Agent ◽  
Initial Therapy ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line Therapy ◽  
Platinum Based Chemotherapy ◽  
Biomarker Evaluation

Non–small cell lung cancer (NSCLC) can no longer be considered as one disease, nor can it be treated as one. Understanding tumor histology in NSCLC is critical to understanding optimal biomarker evaluation and initial therapy. Proper biomarker evaluation includes both evaluation of PD-L1 status, as well as testing for actionable oncogenic drivers such as EGFR, ALK, ROS1, BRAF, Met Exon 14, RET, and NTRK. For patients with NSCLC and a driver oncogene, preferred treatment is targeted therapy. Conversely, for those without an oncogenic driver, preferred initial treatment is pembrolizumab in combination with chemotherapy for patients with low PD-L1 expression (1%–49%) or as a single-agent for high PD-L1 expression (≥50%). For small cell lung cancer (SCLC), the first major NCCN Guideline changes occurred in 2019, with the addition of either atezolizumab or durvalumab to platinum-based chemotherapy and etoposide as first-line therapy for patients with extensive-stage SCLC.

scholarly journals P01.09 Improved Outcomes With Ramucirumab & Docetaxel in Metastatic Non-Small Cell Lung Cancer After Failure of Immunotherapy

2021 ◽  
Vol 16 (3) ◽  
pp. S239-S240
Author(s):  
R. Dawar ◽  
K. Gawri ◽  
E. Rodriguez ◽  
V. Thammineni ◽  
E. Saul ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Improved Outcomes

Randomized Phase II Study of Bevacizumab in Combination With Chemotherapy in Previously Untreated Extensive-Stage Small-Cell Lung Cancer: Results From the SALUTE Trial

2011 ◽  
Vol 29 (16) ◽  
pp. 2215-2222 ◽  
Author(s):  
David R. Spigel ◽  
Peter M. Townley ◽  
David M. Waterhouse ◽  
Liang Fang ◽  
Ibrahim Adiguzel ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Placebo Group ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Single Agent ◽  
Small Cell ◽  
Small Cell Lung ◽  
Randomized Phase Ii ◽  
Extensive Stage

PurposeBecause of promising efficacy signals in single-arm studies, a placebo-controlled, double-blind, randomized phase II trial was designed to assess the efficacy and safety of adding bevacizumab to first-line standard chemotherapy for treatment of extensive-stage small-cell lung cancer (SCLC).Patients and MethodsPatients with SCLC were randomly assigned to receive bevacizumab or placebo, with cisplatin or carboplatin plus etoposide, for four cycles followed by single-agent bevacizumab or placebo until progression or unacceptable toxicity. The primary end point was progression-free survival (PFS).ResultsFifty-two patients were randomly assigned to the bevacizumab group and 50 to the placebo group; 69% versus 66%, respectively, completed four cycles of therapy. Median PFS was higher in the bevacizumab group (5.5 months) than in the placebo group (4.4 months; hazard ratio [HR], 0.53; 95% CI, 0.32 to 0.86). Median overall survival (OS) was similar for both groups (9.4 v 10.9 months for bevacizumab and placebo groups, respectively), with an HR of 1.16 (95% CI, 0.66 to 2.04). Overall response rates were 58% (95% CI, 43% to 71%) for the bevacizumab group and 48% (95% CI, 34% to 62%) for the placebo group. Median duration of response was 4.7 months for the bevacizumab group and 3.2 months for the placebo group. In the bevacizumab and placebo groups, 75% versus 60% of patients, respectively, experienced one or more grade 3 or higher adverse events. No new or unexpected safety signals for bevacizumab were observed.ConclusionThe addition of bevacizumab to cisplatin or carboplatin plus etoposide for treatment of extensive-stage SCLC improved PFS, with an acceptable toxicity profile. However, no improvement in OS was observed.

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