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Luis E Raez
Moderator of
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MS 05 - Clinical Issues of Immune Checkpoint Inhibitors (ID 527)
- Event: WCLC 2017
- Type: Mini Symposium
- Track: Immunology and Immunotherapy
- Presentations: 6
- Moderators:Luis E Raez, Nico Van Zandwijk
- Coordinates: 10/16/2017, 15:45 - 17:30, Main Hall
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MS 05.01 - How to Evaluate the Efficacy of IO? (ID 7658)
15:45 - 16:00 | Presenting Author(s): Frances A Shepherd
- Abstract
- Presentation
Abstract not provided
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MS 05.02 - First-line versus Second-Line Anti-PD-(L)1 Therapy for Patients with Positive PD-L1 Expression (ID 7659)
16:00 - 16:15 | Presenting Author(s): Fabrice Barlesi
- Abstract
- Presentation
Abstract:
Lung cancer is the leading cause of cancer-related deaths in other Western countries, with more than 1.8 million new cases and 1.5 million deaths worldwide in 2012 (Globocan, 2012). Recent advances in the management of NSCLC have included use of therapies targeting oncogenes (EGFR, BRAF or HER2 mutations, ALK or ROS1 rearrangements) but molecular alteration is currently detected in only the half of the patients with non-squamous NSCLC (Barlesi et al., 2016). Immune check point inhibitors (ICI), the first of which targeted the lymphocyte cell surface inhibitory receptor PD-1 or its ligand PD-L1, have recently become available and have been shown to provide an overall survival advantage over standard second-line chemotherapy (Borghaei et al., 2015; Brahmer et al., 2015; Herbst R et al, Lancet 2016; Rittmeyer et al, 2016), and more recently over first-line standard chemotherapy in monotherapy for a small subgroup driven by PD-L1 expression (Reck et al., 2016) or in combination regardless of PD-L1 expression (Langer et al, Lancet Oncol 2016), for both squamous and non-squamous NSCLC. Unfortunately, the long-term overall survival benefit is driven by only about 20-25% of the patients. PD-L1 tumor expression has been proposed to guide the patients’ selection but remains controversial (Kerr K, 2016). However, PD-L1 tumor expression of more than 1% and 50% is mandatory for the use of pembrolizumab monotherapy in second and first-line, respectively. Therefore, how to choose the best way to use ICIs for advanced NSCLC patients? Many aspects may be considered and will be discussed during the session including the PD-L1 expression and other potential predictive biomarkers (as tumor mutational burden), the current contra-indications to ICIs, the potential suspected factors predicting a higher risk of rapid progression on ICIs, the potential synergy for the concomitant combination of ICIs with chemotherapy or conversely a sequential use, the side effects for monotherapies and combinations, and the recent data on ICIs combinations versus standard chemotherapy. In summary, the attendees will have the arguments to globally assess the risk/benefit balance in using ICIs first or at resistance to chemotherapy and discuss the chosen strategies with their patients.
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MS 05.03 - Rational IO/IO Combinations (ID 8120)
16:15 - 16:30 | Presenting Author(s): Tony SK Mok
- Abstract
- Presentation
Abstract not provided
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MS 05.04 - Practical Approach to Combination of Chemotherapy with IO (ID 7660)
16:30 - 16:45 | Presenting Author(s): Yuichiro Ohe
- Abstract
- Presentation
Abstract:
Combination of chemotherapy with immune-check point inhibitor is considered to be one of the most promising strategy to improve efficacy of immune-check point inhibitors. Several clinical trials of chemotherapy with immune-check point inhibitor are conducted and the results have been reported. KEYNOTE-021 cohort G is a randomised, open-label, phase 2 cohort of a multicohort study assessed whether the addition of pembrolizumab to carboplatin and pemetrexed improves efficacy in patients with advanced non-squamous NSCLC. Thirty-three (55%; 95% CI 42–68) of 60 patients in the pembrolizumab plus chemotherapy group achieved an objective response compared with 18 (29%; 18–41) of 63 patients in the chemotherapy alone group (p=0·0016). Progression-free survival (PFS) was significantly longer with pembrolizumab plus chemotherapy compared with chemotherapy alone (HR 0·53 [95% CI 0·31–0·91]; p=0·010). Median PFS was 13·0 months for pembrolizumab plus chemotherapy and 8·9 months for chemotherapy alone. The FDA has granted an accelerated approval to pembrolizumab for use in combination with pemetrexed plus carboplatin as a frontline treatment for patients with metastatic or advanced non-squamous NSCLC, regardless of PD-L1 expression. Antiangiogenic monoclonal antibodies, bevacizumab and ramucirumab that are currently approved for use in the treatment of NSCLC. Bevacizumab, in addition to platinum-based chemotherapy is widely used for the first-line treatment of advanced, metastatic, or recurrent NSCLC, excluding squamous cell carcinoma. VEGF influences lymphocyte trafficking across endothelia to the tumor by inhibiting lymphocyte adhesion and VEGF has a systemic effect on immune-regulatory cell function through multiple mechanisms, such as Tregulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs); suppression of dendritic cell maturation; and inhibition of T-cell development from hematopoietic progenitor cells. Thus, combination of antiangiogenic monoclonal antibody and immune-check point inhibitor is potentially synergistic. National Cancer Center Hospital conducted a single-center phase Ib study investigated the tolerability, safety, and pharmacokinetics of nivolumab combined with standard chemotherapy in patients with advanced NSCLC. In this trial, nivolumab with gemcitabine/cisplatin, pemetrexed/cisplatin, paclitaxel/carboplatin/bevacizumab, or docetaxel were evaluated for six patients each arm. Combination of nivolumab and chemotherapy showed an acceptable toxicity profile and encouraging antitumor activity in patients with advanced NSCLC. Although small number of patients, nivolumab with paclitaxel/carboplatin/bevacizumab seems to be most promising with higher response rate and longer PFS. Based on these data, phase III study of paclitaxel/carboplatin/bevacizumab with/without nivolumab for advanced non-squamous NSCLC is ongoing.
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MS 05.05 - Continuation of Immunotherapy in Post-Progressive Disease (ID 7661)
16:45 - 17:00 | Presenting Author(s): David R. Gandara
- Abstract
- Presentation
Abstract not provided
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MS 05.06 - Brain Metastasis: Rationale and Efficacy with IO (ID 7662)
17:00 - 17:15 | Presenting Author(s): Ignacio Gil-Bazo
- Abstract
- Presentation
Abstract:
The development of metastases from a primary tumor is the ultimate cause of death in most of patients with cancer. In a non-small cell lung cancer (NSCLC) series of 236 patients with advanced disease, brain metastasis appeared to be the second leading site of metastasis after bone (1). In fact, 31.8% of the patients presented brain metastasis at onset and a total of 42.8% of all patients included developed brain metastasis at any time point (1). Despite recent advances in the treatment of patients with NSCLC, CNS infiltration remains a frequent complication leading to impaired quality of life and shortened survival among NSCLC patients. In the era of personalized medicine for patients harboring oncogenic driver mutations, CNS infiltration has become an especially relevant clinical issue. In fact, an apparent higher incidence of brain metastasis at onset, among patients with molecular alterations, in particular for ALK + tumors has been reported (2). In addition, a higher cumulative incidence of CNS involvement overtime during treatment with targeted agents has been shown and CNS may be the only site of progression to first or second-line tailored therapies. Unfortunately however, most patients with advanced NSCLC present tumors lacking druggable oncogenic driver aberrations. In 2011, the tumors’ capacity of avoiding immune destruction was recognized as a new emerging hallmark of cancer. More recently, the constellation of interactions between tumor cells and the immune environment around them has definitely emerged as a potential and valuable source of innumerable novel anti-cancer targets. From the clinical perspective, treatment with immune checkpoint inhibitors targeting programmed-cell death 1 (PD-1) and its ligand (PDL-1) represent the best treatment option for many patients with advanced NSCLC in first-line (3) and most of them in second-line (4-6) due to an improved quality of life and a significant survival benefit. Unfortunately, most phase II randomized/phase III clinical trials assessing the efficacy of monoclonal antibodies against PD-1 (3,4,6) and PDL-1 (5) immune checkpoints in second or first-line settings excluded patients with active or untreated brain metastasis. Additionally, no data on the evolution of previously locally treated CNS lesions during immunotherapy have been provided, nor information revealing the sites of distant progression in patients on the study arm experiencing progression disease to the treatment. The only available results in this regard are reflected in KEYNOTE-024 trial in which the subgroup analysis showed a statistically significant benefit in terms of progression-free survival for patients without baseline brain metastasis on pembrolizumab compared to non-significant differences among patients with brain involvement receiving the PD-1 blocker (3). More interestingly, Goldberg et al. reported the only direct evidence on the potential activity of an immune checkpoint inhibitor against brain metastasis from NSCLC in a non-randomized, open label, phase II clinical trial (7). The study enrolled 36 patients with untreated brain metastases from melanoma (18 patients) or NSCLC (18 patients) receiving pembrolizumab monotherapy. Patients were given 10 mg/kg pembrolizumab every 2 weeks until progression and the primary endpoint was brain metastasis response assessed in all treated patients. In the preliminary results reported, a brain metastasis response was achieved in four (22%; 95% CI 7–48) of 18 patients with melanoma and six (33%; 14–59) of 18 patients with NSCLC. Despite the low number of patients included, this remarkable activity shown by pembrolizumab among brain metastases in patients with NSCLC warrants further investigation in larger series and prompt the analysis of the anatomic, molecular and immune factors involved in those responses. Other studies have focused their attention in the immune microenvironment of the brain in an attempt to unravel the theoretical activity of an immune-directed therapeutic approach. Berghoff at al. investigated tumor-infiltrating lymphocytes (TIL) subsets and their prognostic impact in 116 brain metastases (BM) from different tumor type’s specimens using immunohistochemistry for CD3, CD8, CD45RO, FOXP3, PD1 and PD-L1 (8). Interestingly enough, they found TIL infiltration in 115/116 (99.1%) BM specimens. PD-L1 expression was evident in 19/67 (28.4%) BM specimens and showed no correlation with TIL density (p > 0.05). High infiltration was most frequently observed for CD3+ TILs (95/116; 81.9%) and least frequently for PD1+ TILs (18/116; 15.5%; p < 0.001). Highest TIL density was observed in melanoma, followed by renal cell cancer and lung cancer BM (p < 0.001). More importantly, the density of CD3+, CD8+, and CD45RO+ TILs showed a positive and significant correlation with favorable median overall survival (OS) times. The same group has found TIL infiltration and PD-L1 expression as a common feature in Small-cell Lung Cancer (SCLC) BM. In addition, the presence of CD45RO+ memory T-cells and PD-L1+ TILs in SCLC BM seemed to be associated with favorable survival times suggesting an active immune microenvironment in SCLC BM (9). Takamori et al., evaluated the discordance in PD-L1 expression between primary and metastatic lesions and analyzed the association between the discordance and other clinical factors in 21 NSCLC patients (10). Remarkably, among the 16 patients with brain metastases, in three of them there was a good correlation in PDL-1 expression between the primary tumor and the brain metastasis. In other two patients however, positive PDL-1 primary lesions produced PDL-1 brain metastases. Interestingly enough, in two patients with PDL-1 negative NSCLC undergoing radiation therapy for brain metastases followed by surgical resection of BM, irradiated lesions turned to be positive for PDL-1 expression suggesting a potential capacity of radiotherapy to induce PDL-1 expression in BM (10). In fact, these observations along with several preclinical findings have paved the way for the design of clinical trials combining radiation therapy and immune checkpoint inhibitors against brain metastases. In summary, here we present and discuss the most relevant evidences about the particular immune microenvironment of the brain, the clinical activity of immune checkpoint inhibitors against NSCLC brain metastasis as well as their potential combination with local radiation therapy and the hypothetical use of TIL infiltrates and PDL-1 expression as predictive biomarkers for response of brain metastases to immunotherapy. Several clinical cases illustrating these evidences will be also presented and discussed. References 1. Castanon E, Rolfo C, Vinal D, Lopez I, Fusco JP, Santisteban M, et al. Impact of epidermal growth factor receptor (EGFR) activating mutations and their targeted treatment in the prognosis of stage IV non-small cell lung cancer (NSCLC) patients harboring liver metastasis. J Transl Med. 2015;13:257. 2. Kang HJ, Lim HJ, Park JS, Cho YJ, Yoon HI, Chung JH, et al. Comparison of clinical characteristics between patients with ALK-positive and EGFR-positive lung adenocarcinoma. Respir Med. 2014;108(2):388-94. 3. Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016;375(19):1823-33. 4. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015;373(17):1627-39. 5. Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, et al. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016;387(10030):1837-46. 6. Herbst RS, Baas P, Kim DW, Felip E, Perez-Gracia JL, Han JY, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540-50. 7. Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, et al. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. Lancet Oncol. 2016;17(7):976-83. 8. Berghoff AS, Fuchs E, Ricken G, Mlecnik B, Bindea G, Spanberger T, et al. Density of tumor-infiltrating lymphocytes correlates with extent of brain edema and overall survival time in patients with brain metastases. Oncoimmunology. 2016;5(1):e1057388. 9. Berghoff AS, Ricken G, Wilhelm D, Rajky O, Widhalm G, Dieckmann K, et al. Tumor infiltrating lymphocytes and PD-L1 expression in brain metastases of small cell lung cancer (SCLC). J Neurooncol. 2016;130(1):19-29. 10. Takamori S, Toyokawa G, Okamoto I, Takada K, Kozuma Y, Matsubara T, et al. Discrepancy in Programmed Cell Death-Ligand 1 Between Primary and Metastatic Non-small Cell Lung Cancer. Anticancer Res. 2017;37(8):4223-8.
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Author of
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MA 15 - Lung Cancer Biology II (ID 670)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Biology/Pathology
- Presentations: 1
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MA 15.02 - Plasma CfDNA next Generation Sequencing in Non-Small Cell Lung Cancer: Clinical Outcomes and Comparison to Tissue (ID 9502)
15:50 - 15:55 | Presenting Author(s): Luis E Raez
- Abstract
- Presentation
Background:
Next-generation sequencing (NGS) of cell-free DNA (cfDNA) in plasma can be an alternative or complement to tissue biopsy for genomic analysis of non-small cell lung cancer (NSCLC), particularly for identifying driver and resistance alterations. We presented preliminary data in 67 patients comparing NGS in plasma vs. tissue (Santos et al. JTO; 11:10, S199-200) and found EGFR mutation agreement of 68% between plasma and tissue. We now present an expanded patient cohort with more extensive concordance analysis, longer follow-up, and clinical outcomes.
Method:
We analyzed data from advanced (stage III/IV) NSCLC patients seen at three cancer centers in Florida (US; Memorial Cancer Institute, Florida Hospital Cancer Center, Mount Sinai Cancer Center) that had alterations detected on Guardant360 (G360) testing through January 2017. G360 is a plasma cfDNA NGS assay that detects single nucleotide variations, amplifications, fusions, and indels in targeted genes using massively parallel digital sequencing; panel composition expanded from 54 to 73 genes over the course of the cohort. NGS performed on solid tumor biopsies from each subject were reviewed for comparison where available but may not have been collected contemporaneously to the plasma samples. Treatment information and clinical outcomes were collected for those patients with actionable mutations per NCCN guidelines (v3.2017).
Result:
A total of 190 G360 test results on 171 unique patients were identified (some patients underwent serial testing at multiple clinical timepoints, e.g. progression). Forty percent of patients were male; the median age was 65 (32-94). Excluding variants of uncertain significance, patients were most likely to have cfDNA alterations in TP53 (44%), EGFR (21%), KRAS (19%), BRAF (8%), and MET (8%). Forty-seven patients (28%) had at least one actionable mutation identified on G360, including SNVs, indels, fusions, and amplifications. Preliminary clinical outcomes data include durable (³10 months) partial responses on targeted therapy based on multiple plasma-detected alterations in EGFR and BRAF V600E; complete analysis will be presented at the meeting.
Conclusion:
Liquid biopsy plays an important role in genomic analysis of NSCLC, offering reliable information to guide therapeutic decision-making. Results in our cohort include a noteworthy proportion of patients with highly actionable mutations, like EGFR drivers and targetable resistance mutations, and G360 offers an alternative to tissue biopsy in these patients.
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OA 11 - Reducing Burden: Patient-Centered Care (ID 682)
- Event: WCLC 2017
- Type: Oral
- Track: Nursing/Palliative Care/Ethics
- Presentations: 1
- Moderators:Beth Ivimey, E. Bernicker
- Coordinates: 10/18/2017, 11:00 - 12:30, Room 313 + 314
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OA 11.07 - Enhancing Lung Cancer (LC) Care in the Community Setting Through a Patient Advocacy 'Centers of Excellence' (COE) Program (ID 10423)
12:05 - 12:15 | Author(s): Luis E Raez
- Abstract
- Presentation
Background:
The Addario Lung Cancer Foundation’s community hospital COE Program seeks to improve LC outcomes by catalyzing the dissemination of coordinated, evidence-based multidisciplinary care incorporating institutional performance benchmarks across the LC care continuum. The COE program is a network of community-level institutions committed to objectively-measured quality improvement through annual cycles of data collection, comparative analysis and feedback. We analyzed 2016 benchmarks, comparing COE and non-COE programs.
Method:
The annual COE Impact Survey instrument includes an 81-item questionnaire administered by ZoomRx, an independent survey company. Respondents were key institutional representatives of COE- and community-level non-COE institutions. The survey measured the care continuum from screening to end-of-life care. Patient- and institutional-level data for 2016 were analyzed.
Result:
Cohort- 15 COE v 15 non-COE, mean number of annual patients per site 264 v 279; % stage III/IV patients 62 v 74; Medicare-enrolled patients, 54% v 40%; patients 61-80 years 61% v 46%; % patients who encountered financial difficulty in 2016, 42% v 34%. Institutional screening/nodule management programs: 71% of COE v 60% of non-COE programs had a low-dose CT (LDCT) screening program; 86% v 80% used a standard protocol to follow patients with suspicious nodules; 35% v 28% LDCT patients were requested to follow up on suspicious findings; 76% v 67% patients actually followed up. Diagnostic biopsy of LC was by minimally invasive endobronchial approaches in 47% v 15%. Programmatic management of patients with stage III/IV disease: 75% v 49% of patients with stage III/IV disease were reviewed at a Tumor Board and 74% v 62% had a palliative care discussion. Molecular testing was used in 51% v 81%. In patients undergoing molecular testing, institutional use of blood-based ‘liquid biopsies’ was 86% v 18% and next generation sequencing of tissue 67% v 58%. Clinical trials enrollment rates were 20% v 13%, but 18% v 31% of patients were not screened for clinical trials. In weighting factors driving treatment selection on a 100-point relative scale, COE programs weighted ‘quality of life’ (39% v 26%) and ‘patient expense’ (22% v 11%) more than non-COE programs. Non-COE programs weighted ‘product attributes’ (efficacy and safety) 48% (v 14% in COE) more.
Conclusion:
Differences exist in the approach to LC care between COE and non-COE programs. Future iterations of the COE Impact Survey will enable a data-driven approach to disseminating high quality LC care at community-level institutions, where the majority of patients seek care for lung cancer.
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P2.01 - Advanced NSCLC (ID 618)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:00 - 16:00, Exhibit Hall (Hall B + C)
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P2.01-056 - Use of Cell-Free Circulating RNA (cfRNA) Expression of PD-L1 and ERCC1 in Plasma to Monitor Response to Therapy in NSCLC (ID 9038)
09:00 - 09:00 | Presenting Author(s): Luis E Raez
- Abstract
Background:
There is an unmet need to evaluate tumor response by other means than radiology tests. Cell-free circulating tumor RNA (cfRNA) can be extracted from plasma of cancer patients (pts); measuring dynamic changes in gene expression and levels of b-actin; cfRNA (per ml of plasma) as a proxy for total cfRNA in metastatic patients has shown great potential for evaluating disease status and predicting outcome to anti-tumoral therapy in advance of imaging. We have previously shown that high levels of PD-L1 cfRNA expression correlates well with positive response to immunotherapies including nivolumab in pts with NSCLC.
Method:
Blood was drawn from pts at approximately 6-week intervals under various therapies, with CT scans at 3-month intervals. Total cfRNA was extracted from patient plasma and reverse transcribed to cDNA. Levels of b-actin, ERCC1 and PD-L1 were quantitated across multiple blood draws by RT-qPCR and correlated with pt response (PR/SD/PD), as determined by CT scans.
Result:
A total of 24 NSCLC patients were enrolled in a 1-year clinical study. Non-SCC comprised 87% (21/24). 19 pts completed the first two cycles of therapy. 1 pt with PR had decreasing levels of cfRNA, 10 pts achieved SD with decreasing or no change while 6/8 pts with PD had increasing levels of cfRNA. CfRNA levels were predictive of disease status about 4 weeks in advance of imaging in 6/19 pts and matched with disease status in 8/19 pts (74% ). Dynamic changes in PD-L1 expression correlated with response to nivolumab in 3/4 pts. In 2/4 pts with SD, PD-L1 remained undetected after therapy, whereas 1 patient continued to have PD despite loss of PD-L1. PD-L1 was undetectable in a pt initially with PD on nivolumab who achieved SD after one cycle of nivolumab plus radiation. Changing ERCC1 expression correlated with platinum-based therapy outcome in 8/8 patients. 4/4 patients with PD on pemetrexed/carboplatin had an increase in ERCC1. 4/4 patients with lower or decreasing levels of ERCC1 achieved PR or SD. In the only patient achieving PR, ERCC1 became undetectable during treatment.
Conclusion:
We found significant concordance between clinical response and changes in plasma cfRNA levels in NSCLC pts (74%). Levels of PD-L1 expression correlated with response in 3/4 pts treated with nivolumab . ERCC1 levels were predictive of outcome to platinum based therapy for 8/8 patients. ERCC1 and PD-L1 expression in cfRNA can be used to monitor response to platinum-based and immuno-therapy.
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P2.07 - Immunology and Immunotherapy (ID 708)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.07-052 - Detection of KRAS Mutation in Blood Predicts Favorable Response to Immunotherapy in NSCLC (ID 10469)
09:30 - 09:30 | Author(s): Luis E Raez
- Abstract
Background:
Immunotherapy has brought new therapeutic options to non-small cell lung cancer. PD-L1 has been established as the primary clinical biomarker for PD-1/PD-L1 targeting antibodies, with higher expression correlation with superior therapy responses. Tumor mutational burden and other biomarkers have been similarly implicated in prediction of immunotherapy responses. These markers are obtained from tumor tissue based on immuno-histochemistry or next generation sequencing. Availability of tissue has remained a significant clinical challenge. Mutations in KRAS have been reported to correlate with improved survival. We interrogated our data base to investigate whether KRAS detected in blood could serve as a surrogate marker for immunotherapy selection.
Method:
We screened a total of 239 cases of non-small cell lung cancer with positive tissue evaluation. 89/239 cases tested positive for presence of a KRAS mutation. 56 KRAS mutant cases of NSCLC, matched tissue (NGS and PD-L1) and blood (NGS) analyses were available. 17 cases had PD-L1 expression of greater than 50% on IHC. 39 cases had PD-L1 expression of less than 50%, defined as low expression. 34 patients had received single agent, PD-1 targeting immunotherapy (nivolumab or pembrolizumab). We reviewed these cases with low PD-L1 expression treated with immunotherapy in a retrospective analysis for clinical outcomes.
Result:
In the cohort with low PD-L1 low/KRAS mutant status, a response rate (PR+CR) of 53% (n=18) was observed, including 13% (n=5) complete responses. The average progression-free survival in this subset was 11.1 month. KRAS status correlated expectedly with prior or current smoking history (97%), and elevated tumor mutational load (16 mutations per megabase).
Conclusion:
Selection of appropriate candidates for immunotherapy has remained a clinical challenge. In our analysis, liquid biopsy was obtained without complication and correlated strongly between blood and tissue. Compared to historical controls, KRAS mutant status appears to have a higher response rate and prolonged progression-free survival independent of PD-L1 status. In addition to previously established PD-L1 and TML markers, our data supports a role of KRAS as a surrogate marker for immunotherapy response that should be investigated in prospective clinical trials.
