Abstract 1064P
Background
Development of new therapies for lung cancer treatment has improved survival rates in aNSCLC pts. Certain pts subgroups do not benefit from these treatments and there is lacking evidence on why these show different survival outcomes. We aimed to identify an association between non-driver mutational patterns and pts subgroups of special interest.
Methods
Flatiron Clinico-Genomic and FoundationCORE® databases (US-based) were used to analyse non-driver mutations prevalence with prognostic value significantly associated with efficacy outcomes in a previous study with aNSCLC pts. Multivariable logistic regression models adjusted for key co-variates were used to evaluate the presence of non-driver mutation in four subgroups described in literature: fast progressors (FP, median progression free survival [mPFS]< 3 months), long term survivors (LTS, mPFS > 12 months), females and never-smokers.
Results
FP showed a significantly higher prevalence of STK11, KEAP1 and CDKN2A/B mutations compared with non-FP (OR > 1, Table). We observed a significantly lower prevalence of STK11, KEAP1, CDKN2A/B, and FGFR mutations (OR < 1, Table), and a higher prevalence of KRAS mutations in LTS (OR 1.43). APC (OR 0.53) and FGFR (OR 0.58) mutations were less frequent in women, while KRAS mutations were more frequent (OR 1.98). STK11 and KEAP1 mutations were significantly more prevalent in smokers (OR > 1, Table). There was a trend towards lower prevalence of FGFR and higher prevalence of HRAS in non-smokers. See table. Table: 1064P
Prevalence of selected non-driver mutations in all patients
| STK11 | KEAP1 | CDKN2A/B | ||||||||||||||||
| Mutated | % | Not mutated | % | OR | p | Mutated | % | Not mutated | % | OR | p | Mutated | % | Not mutated | % | OR | p | |
| Non-FP | 294 | 1385 | 78.7 | 1.7 | <0.001 | 180 | 13.1 | 1499 | 86.9 | 1.6 | <0.001 | 482 | 31 | 1197 | 69 | 1.28 | 0.002 | |
| FP | 338 | 21.3 | 945 | 207 | 1076 | 436 | 847 | |||||||||||
| Non-LTS | 586 | 1919 | 78.7 | 0.4 | <0.001 | 346 | 13.1 | 2159 | 86.9 | 0.6 | 0.004 | 803 | 31 | 1702 | 69 | 0.71 | 0.003 | |
| LTS | 46 | 21.3 | 411 | 41 | 416 | 115 | 342 | |||||||||||
| Male | 333 | 1267 | 78.7 | 1.1 | 0.48 | 222 | 13.1 | 1378 | 86.9 | 0.9 | 0.15 | 525 | 31.3 | 1075 | 68.7 | 0.86 | 0.05 | |
| Female | 306 | 21.3 | 1093 | 169 | 1230 | 413 | 986 | |||||||||||
| Non-smoker | 16 | 132 | 78.7 | 2.3 | 0.001 | 5 | 13.1 | 143 | 86.9 | 4.5 | <0.001 | 53 | 31.3 | 95 | 68.7 | 0.81 | 0.22 | |
| Smoker | 623 | 21.3 | 2228 | 386 | 2465 | 885 | 1966 |
Conclusions
STK11, KEAP1 and CDKN2A/B mutations were significantly associated with fast progression. Along with FGFR mutations, these were significantly associated with a shorter survival. Women were less likely to harbour mutations in these genes, while smokers showed a higher prevalence. Our results may assist in identifying aNSCLC pts who respond better to treatment.
Clinical trial identification
Editorial acknowledgement
The authors would like to thank Dr. Víctor Latorre, at Medical Statistics Consulting, for medical writing services.
Legal entity responsible for the study
Roche Farma, S.A.
Funding
Roche Farma, S.A.
Disclosure
M. Provencio Pulla: Financial Interests, Advisory Board: Roche, Merck, BMS, AstraZeneca, Lilly, Pfizer, Bayer, Amgen, Janssen, Takeda, Sanofi; Financial Interests, Invited Speaker: Roche, Merck, BMS, Takeda; Financial Interests, Research Grant, Funding self: Roche, BMS, Takeda; Financial Interests, Research Grant, Funding institution: Roche, BMS. D. Perez Parente: Financial Interests, Full or part-time Employment: Roche. B. Campos Balea: Financial Interests, Invited Speaker: Roche, Merck, BMS, AstraZeneca, Sanofi; Financial Interests, Other, Travel/Accommodation/Expenses: Roche, BMS, Pfizer, Boehringer; Financial Interests, Invited Speaker, Travel/Accommodation/Expenses: Lilly. D. Rodriguez Abreu: Financial Interests, Advisory Board: Roche, Merck, BMS, AstraZeneca, Pfizer, Boehringer, Takeda; Financial Interests, Invited Speaker: Roche, Merck, BMS, AstraZeneca, Boehringer, Takeda; Financial Interests, Other, Travel/Accommodation/Expenses: Roche, Merck, BMS, AstraZeneca. H. Hasan: Financial Interests, Full or part-time Employment: Genentech. S. Olson: Financial Interests, Full or part-time Employment: Roche. N. Pal: Financial Interests, Full or part-time Employment: Genentech. S. Wilkinson: Financial Interests, Full or part-time Employment: Roche. F. De Oro Pulido: Financial Interests, Full or part-time Employment: Roche. P. Ruiz Gracia: Financial Interests, Full or part-time Employment: Roche. M. Cobo Dols: Financial Interests, Advisory Board: Roche, BMS, AstraZeneca, Pfizer, Boehringer; Financial Interests, Other, Travel/Accommodation/Expenses: Roche, BMS, AstraZeneca.