The association of nutritional and inflammatory biomarkers with overall survival in patients with non-small-cell lung cancer treated with immune checkpoint inhibitors.

OBJECTIVES: Pretreatment biomarkers are needed to identify patients with non-small-cell lung cancer (NSCLC) likely to have worse survival. This ensures that only patients with a real chance of benefit receive immune checkpoint inhibitor (ICI) treatment. In this study, we examined the associations of baseline nutritional and inflammatory biomarkers with overall survival in a real-world cohort of NSCLC patients who received ICIs. MATERIALS AND METHODS: We used prospectively collected data from the OncoLifeS data biobank. The cohort included 500 advanced-stage NSCLC patients treated with ICIs from May 2015 to June 2021. Biomarkers were evaluated within 2 weeks before ICI treatment: neutrophil-to-lymphocyte ratio, C-reactive protein (CRP), Glasgow prognostic score, CRP/albumin ratio (CAR), prognostic nutritional index (PNI), and advanced lung cancer inflammation index. For each biomarker, low- and high-risk groups were defined using literature-based cut-offs. Adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were estimated using adjusted survival analysis. RESULTS: Most patients were male (60.8%), the mean baseline age was 65 ± 9 years, and 88% had stage IV disease. For each biomarker, low-risk patients had better overall survival (all, p < 0.001), with CAR and PNI showing the strongest associations. In multivariable analyses a combined CAR/PNI risk score had a stronger association with overall survival (aHR 3.09, 95% CI 2.36-4.06) than CAR alone (aHR 2.22, 95% CI 1.79-2.76) or PNI alone (aHR 2.09, 95% CI 1.66-2.61). CONCLUSION: These results highlight the potential value of nutritional and inflammatory biomarkers, in particular CAR and PNI, in identifying NSCLC patients with highest mortality risk before starting ICI treatment.

Reliability of panel-based mutational signatures for immune-checkpoint-inhibition efficacy prediction in non-small cell lung cancer.

OBJECTIVES: Mutational signatures (MS) are gaining traction for deriving therapeutic insights for immune checkpoint inhibition (ICI). We asked if MS attributions from comprehensive targeted sequencing assays are reliable enough for predicting ICI efficacy in non-small cell lung cancer (NSCLC). METHODS: Somatic mutations of m = 126 patients were assayed using panel-based sequencing of 523 cancer-related genes. In silico simulations of MS attributions for various panels were performed on a separate dataset of m = 101 whole genome sequenced patients. Non-synonymous mutations were deconvoluted using COSMIC v3.3 signatures and used to test a previously published machine learning classifier. RESULTS: The ICI efficacy predictor performed poorly with an accuracy of 0.51-0.09+0.09, average precision of 0.52-0.11+0.11, and an area under the receiver operating characteristic curve of 0.50-0.09+0.10. Theoretical arguments, experimental data, and in silico simulations pointed to false negative rates (FNR) related to panel size. A secondary effect was observed, where deconvolution of small ensembles of point mutations lead to reconstruction errors and misattributions. CONCLUSION: MS attributions from current targeted panel sequencing are not reliable enough to predict ICI efficacy. We suggest that, for downstream classification tasks in NSCLC, signature attributions be based on whole exome or genome sequencing instead.

Using genomic scars to select immunotherapy beneficiaries in advanced non-small cell lung cancer.

In advanced non-small cell lung cancer (NSCLC), response to immunotherapy is difficult to predict from pre-treatment information. Given the toxicity of immunotherapy and its financial burden on the healthcare system, we set out to identify patients for whom treatment is effective. To this end, we used mutational signatures from DNA mutations in pre-treatment tissue. Single base substitutions, doublet base substitutions, indels, and copy number alteration signatures were analysed in [Formula: see text] patients (the discovery set). We found that tobacco smoking signature (SBS4) and thiopurine chemotherapy exposure-associated signature (SBS87) were linked to durable benefit. Combining both signatures in a machine learning model separated patients with a progression-free survival hazard ratio of 0.40[Formula: see text] on the cross-validated discovery set and 0.24[Formula: see text] on an independent external validation set ([Formula: see text]). This paper demonstrates that the fingerprints of mutagenesis, codified through mutational signatures, select advanced NSCLC patients who may benefit from immunotherapy, thus potentially reducing unnecessary patient burden.

Safety and tolerability of stereotactic radiotherapy combined with durvalumab with or without tremelimumab in advanced non-small cell lung cancer, the phase I SICI trial.

INTRODUCTION: This phase I study primarily addresses the safety and tolerability of Stereotactic radiotherapy on the primary tumor combined with double Immune Checkpoint Inhibition (SICI) in patients with non-small cell lung cancer (NSCLC). Increasing the release of neoantigens by radiotherapy might enhance response to immunotherapy. Especially, by targeting trunk mutations in the primary tumor. MATERIALS AND METHODS: In three sequential cohorts, immunotherapy regimes combined with stereotactic body radiotherapy (SBRT) on the primary tumor (1x20 Gy on 9 cc) were studied in stage IIIB/IV NSCLC patients progressing on chemotherapy. The first cohort (n = 3) received durvalumab. The second (n = 6) received a combination of tremelimumab and durvalumab followed by durvalumab monotherapy. The third cohort (n = 6) was similar except that the combination was reversed. Descriptive statistics were used to assess safety parameters and the exploratory outcomes of efficacy. Adverse events were reported using NCI CTCAE version 4.03. Exhaled breath was analyzed at baseline. RESULTS: Fifteen patients were included. Median irradiated volume was 9.13 cc, on a median primary tumor volume of 79 cc. There were seven patients with grade 1-2, and two patients with grade 3 treatment related adverse events. There was 1 dose limiting toxicity (colitis) with double immunotherapy. CONCLUSION: The combination of SBRT to the primary tumor and double immunotherapy in advanced NSCLC patients is safe and feasible.

Quality of life after treatment with immune checkpoint inhibitors for lung cancer; the impact of age.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have revolutionized lung cancer treatment. However, it remains unclear as to whether changes in Health-Related Quality-of-Life (HRQoL) are associated with the age of lung cancer patients treated using ICIs. This study aimed to evaluate this possible association and to compare ICI-treated patients' HRQoL scores with normative data of an age-matched non-cancer general population. METHODS: Lung cancer patients from the OncoLifeS data-biobank were included if they were treated with ICIs, irrespective of other treatments, at the University Medical Center Groningen between 2015 and 2021 and had completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30), both at the start of ICI treatment and after six months. Association of age as a continuous variable (per 10 years) and changes in HRQoL scores between baseline and 6 months was assessed using multivariable regression analyses. Clinical relevance of differences in HRQoL scores between OncoLifeS and the general population was classified into trivial, small, medium, and large, for three age groups (<60, 60-69 and ≥ 70 years). RESULTS: 151 patients were included with a mean age of 65.8 years. An increase in age per 10 years was associated with a larger decrease in the summary HRQoL score(ß = -3.28,CI95%-6.42;-0.14), physical(ß = -4.8, CI95% -8.71;-0.88), cognitive(ß = -4.51,CI95%-8.24;-0.78), role functioning(ß = -5.41,CI95%-10.78;-0.05), symptom burden(ß = -3.66,CI95%-6.6;-0.73), and smaller negative changes in financial difficulties(ß = 6.5 95 % CI 3.16; 9.85). OncoLifeS HRQoL scores were lower than those of the general population and differences were most often classified as large and medium. CONCLUSION: Older lung cancer patients experience larger deteriorations in most HRQoL domains after 6 months of ICI treatment. Also, these patients showed significantly lower HRQoL scores compared to the general population.

Safety and Efficacy of Extended Interval Dosing for Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer During the COVID-19 Pandemic.

INTRODUCTION: Extended interval (EI) dosing for immune checkpoint inhibitor (ICI) mono- or consolidation therapy initiated due to the COVID-19 pandemic led to a significant reduction in ICI-related site visits for patients with stage III and IV non-small cell lung cancer. Here we report the safety and efficacy compared to standard dose (SD) schedules. METHOD: In this retrospective analysis, patients who received ICI mono- or consolidation therapy, or adjuvant ICI therapy were assessed. Safety and efficacy of EI dosing with data of SD schedules were compared. RESULTS: One hundred seventeen patients received EI dosing for ICI and 88 patients SD. Patient characteristics were comparable. We observed 237 adverse events in the EI dosing cohort versus 118 in the SD group (P= .02). Overall, there was no difference in the occurrence of grade ≥3 adverse events (EI dosing: 21/237 [8.9%]; SD group: 20/118 [17.0%], P = .42), except for the pembrolizumab EI dosing cohort. Of all patients who received an EI dosing schedule, however, only 8 (6.8%) were reduced to SD because of toxicity. In 5 (4.3%) patients ICI was permanently stopped because of severe toxicity compared to 11 (12.5%) discontinuations in the SD group. Short-term treatment interruption occurred with similar frequencies in both groups. Progression-free survival and overall survival were comparable in patients receiving pembrolizumab and in those receiving adjuvant durvalumab. Progression-free survival and OS were better in the EI dosing cohort of nivolumab. CONCLUSION: EI dosing for ICI did not lead to an increase of clinically relevant toxicities resulting in dose reduction and/or treatment discontinuation. Efficacy of EI dosing of pembrolizumab and durvalumab were comparable to SD. Based on our safety and efficacy data EI dosing for ICI seems a safe and effective strategy.

89Zr-pembrolizumab imaging as a non-invasive approach to assess clinical response to PD-1 blockade in cancer.

BACKGROUND: Programmed cell death protein 1 (PD-1) antibody treatment is standard of care for melanoma and non-small-cell lung cancer (NSCLC). Accurately predicting which patients will benefit is currently not possible. Tumor uptake and biodistribution of the PD-1 antibody might play a role. Therefore, we carried out a positron emission tomography (PET) imaging study with zirconium-89 (89Zr)-labeled pembrolizumab before PD-1 antibody treatment. PATIENTS AND METHODS: Patients with advanced or metastatic melanoma or NSCLC received 37 MBq (1 mCi) 89Zr-pembrolizumab (∼2.5 mg antibody) intravenously plus 2.5 or 7.5 mg unlabeled pembrolizumab. After that, up to three PET scans were carried out on days 2, 4, and 7. Next, PD-1 antibody treatment was initiated. 89Zr-pembrolizumab tumor uptake was calculated as maximum standardized uptake value (SUVmax) and expressed as geometric mean. Normal organ uptake was calculated as SUVmean and expressed as a mean. Tumor response was assessed according to (i)RECIST v1.1. RESULTS: Eighteen patients, 11 with melanoma and 7 with NSCLC, were included. The optimal dose was 5 mg pembrolizumab, and the optimal time point for PET scanning was day 7. The tumor SUVmax did not differ between melanoma and NSCLC (4.9 and 6.5, P = 0.49). Tumor 89Zr-pembrolizumab uptake correlated with tumor response (P trend = 0.014) and progression-free (P = 0.0025) and overall survival (P = 0.026). 89Zr-pembrolizumab uptake at 5 mg was highest in the spleen with a mean SUVmean of 5.8 (standard deviation ±1.8). There was also 89Zr-pembrolizumab uptake in Waldeyer's ring, in normal lymph nodes, and at sites of inflammation. CONCLUSION: 89Zr-pembrolizumab uptake in tumor lesions correlated with treatment response and patient survival. 89Zr-pembrolizumab also showed uptake in lymphoid tissues and at sites of inflammation.

Risk factors for adverse events induced by immune checkpoint inhibitors in patients with non-small-cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause serious immune-related adverse events (irAEs). This study aimed to identify risk factors for all types of irAEs induced by ICIs in patients with non-small-cell lung cancer (NSCLC), by systematic review and meta-analyses. METHODS: A systematic search was performed in Pubmed, Embase and Web of Science by two independent reviewers. Studies were selected that included patients with NSCLC and evaluated characteristics of patients with and without irAEs induced by ICIs. Quality and risk of bias of the selected studies were assessed. Random effects meta-analyses were conducted to estimate pooled odds ratios (ORs) for risk factors of developing all type of irAEs, and separately for pneumonitis, interstitial lung disease and severe irAEs. With the objective of exploring sources of heterogeneity, stratified analyses were performed by quality and region. RESULTS: 25 studies met the inclusion criteria. In total, the data of 6696 patients were pooled. 33 different risk factors for irAEs were reported. irAEs of interest were reported for 1653 (25%) of the patients. Risk factors related to the development of irAEs were: C-reactive protein, neutrophil lymphocyte ratio (NLR), use of PD-1 inhibitor, high PD-L1 expression, an active or former smoking status, ground glass attenuation, and a better treatment response. CONCLUSION: The identified risk factors for the development of these irAEs are mostly related to the alteration of the immune system, proinflammatory states and loss of immunological self-tolerance. Patients identified as having a higher risk for irAEs should be monitored more closely.

Treatment goals and changes over time in older patients with non-curable cancer.

PURPOSE: To investigate the treatment goals of older patients with non-curable cancer, whether those goals changed over time, and if so, what triggered those changes. METHODS: We performed a descriptive and qualitative analysis using the Outcome Prioritization Tool (OPT) to assess patient goals across four conversations with general practitioners (GPs) over 6 months. Text entries from electronic patient records (hospital and general practice) were then analyzed qualitatively for this period. RESULTS: Of the 29 included patients, 10 (34%) rated extending life and 9 (31%) rated maintaining independence as their most important goals. Patients in the last year before death (late phase) prioritized extending life less often (3 patients; 21%) than those in the early phase (7 patients; 47%). Goals changed for 16 patients during follow-up (12 in the late phase). Qualitative analysis revealed three themes that explained the baseline OPT scores (prioritizing a specific goal, rating a goal as unimportant, and treatment choices related to goals). Another three themes related to changes in OPT scores (symptoms, disease course, and life events) and stability of OPT scores (stable situation, disease-unrelated motivation, and stability despite symptoms). CONCLUSION: Patients most often prioritized extending life as the most important goal. However, priorities differed in the late phase of the disease, leading to changed goals. Triggers for change related to both the disease (e.g., symptoms and course) and to other life events. We therefore recommend that goals should be discussed repeatedly, especially near the end of life. TRIAL REGISTRATION: OPTion study: NTR5419.

Effects of checkpoint inhibitors in advanced non-small cell lung cancer at population level from the National Immunotherapy Registry.

OBJECTIVE: Phase III studies of checkpoint inhibitors changed the therapeutic landscape for lung cancer. In 2015 the Dutch Society of Chest Physicians (NVALT) introduced a national immunotherapy registry for patients with lung cancer; quality standards for hospitals were implemented. At population level we studied clinical benefit in daily practice and in patients who are underrepresented in phase III trials. MATERIALS AND METHODS: From the initial introduction of checkpoint inhibitors in the Netherlands patients were centrally registered. Educational programs and quality control were provided under supervision of NVALT. The largest immunotherapy providing hospitals were compared to hospitals who provided less checkpoint inhibitors as marker of experience. Patients characteristics, treatment and side effects, response rate and survival were studied. RESULTS: A total of 2676 patients were registered, 2302 with follow up data were evaluated. Between October 2015 and December 2017 a gradual increase from 12 to 30 qualified hospitals showed no major toxicity differences. Toxicity led to a hospital admission rate of 9.1 with an average duration of 10.4 days. Overall tumor response was 21.8 % and median overall survival 12.6 months. Overall survival was not significantly different for patients aged ≥ 75 years, those having brain metastases or selected auto-immune diseases before start checkpoint inhibitors compared to younger patients or those without, respectively. Survival outcomes were worse in patients with PS 2+, non-smokers, and patients who received any palliative radiotherapy (HR 2.1, 95 % CI 1.7-2.7; 1.3, 95 % CI 1.0-1.6 and 1.2, 95 % CI 1.1-1.4, respectively). CONCLUSIONS: Changes in the therapeutic landscape did not lead to major differences in quality of care between hospitals. Elderly patients, those with brain metastases or selected auto-immune disease underrepresented in clinical trials did not do worse on checkpoint inhibitors, except for those with PS 2 + .

EPAC-lung: pooled analysis of circulating tumour cells in advanced non-small cell lung cancer.

INTRODUCTION: We assessed the clinical validity of circulating tumour cell (CTC) quantification for prognostication of patients with advanced non-small cell lung cancer (NSCLC) by undertaking a pooled analysis of individual patient data. METHODS: Nine European NSCLC CTC centres were asked to provide reported/unreported pseudo-anonymised data for patients with advanced NSCLC who participated in CellSearch CTC studies from January 2003 to March 2017. We used Cox regression models, stratified by centres, to establish the association between CTC count and survival. We assessed the added value of CTCs to prognostic clinicopathological models using likelihood ratio (LR) statistics and c-indices. RESULTS: Seven out of nine eligible centres provided data for 550 patients with prognostic information for overall survival. CTC counts of ≥2 and ≥ 5 per 7·5 mL were associated with reduced progression-free survival (≥2 CTCs: hazard ratio [HR] = 1.72, p < 0·001; ≥5 CTCs: HR = 2.21, p < 0·001) and overall survival (≥2 CTCs: HR = 2·18, p < 0·001; ≥5 CTCs: HR = 2·75, p < 0·001), respectively. Survival prediction was significantly improved by addition of baseline CTC count to LR clinicopathological models (log-transformed CTCs p < 0·001; ≥2 CTCs p < 0·001; ≥5 CTCs p ≤ 0·001 for both survival end-points), whereas moderate improvements were observed with the use of c-index models. There was some evidence of between-centre heterogeneity, especially when examining continuous counts of CTCs. CONCLUSIONS: These data confirm CTCs as an independent prognostic indicator of progression-free survival and overall survival in advanced NSCLC and also reveal some evidence of between-centre heterogeneity. CTC count improves prognostication when added to full clinicopathological predictive models.

The distress thermometer as a prognostic tool for one-year survival among patients with lung cancer.

INTRODUCTION: The use of patient-reported outcome measures is increasingly advocated to support high-quality cancer care. We therefore investigated the added value of the Distress Thermometer (DT) when combined with known predictors to assess one-year survival in patients with lung cancer. METHODS: All patients had newly diagnosed or recurrent lung cancer, started systemic treatment, and participated in the intervention arm of a previously published randomised controlled trial. A Cox proportional hazards model was fitted based on five selected known predictors for survival. The DT-score was added to this model and contrasted to models including the EORTC-QLQ-C30 global QoL score (quality of life) or the HADS total score (symptoms of anxiety and depression). Model performance was evaluated through improvement in the -2 log likelihood, Harrell's C-statistic, and a risk classification. RESULTS: In total, 110 patients were included in the analysis of whom 97 patients accurately completed the DT. Patients with a DT score ≥5 (N = 51) had a lower QoL, more symptoms of anxiety and depression, and a shorter median survival time (7.6 months vs 10.0 months; P = 0.02) than patients with a DT score <5 (N = 46). Addition of the DT resulted in a significant improvement in the accuracy of the model to predict one-year survival (P < 0.001) and the discriminatory value (C-statistic) marginally improved from 0.69 to 0.71. The proportion of patients correctly classified as high risk (≥85% risk of dying within one year) increased from 8% to 28%. Similar model performance was observed when combining the selected predictors with QoL and symptoms of anxiety or depression. CONCLUSIONS: Use of the DT allows clinicians to better identify patients with lung cancer at risk for poor outcomes, to further explore sources of distress, and subsequently personalize care accordingly.

Correspondence between primary and secondary care about patients with cancer: a Delphi consensus study.

INTRODUCTION: To provide optimal care for patients with cancer, timely and efficient communication between healthcare providers is essential. In this study, we aimed to achieve consensus regarding the desired content of communication between general practitioners (GPs) and oncology specialists before and during the initial treatment of cancer. METHODS: In a two-round Delphi procedure, three expert panels reviewed items recommended for inclusion on referral and specialist letters. RESULTS: The three panels comprised 39 GPs (42%), 42 oncology specialists (41%) (i.e. oncologists, radiotherapists, urologists and surgeons) and 18 patients or patient representatives (69%). Final agreement was by consensus, with 12 and 35 items included in the GP referral and the specialist letters, respectively. The key requirements of GP referral letters were that they should be limited to medical facts, a short summary of symptoms and abnormal findings, and the reason for referral. There was a similar requirement for letters from specialists to include these same medical facts, but detailed information was also required about the diagnosis, treatment options and chosen treatment. After two rounds, the overall content validity index (CVI) for both letters was 71%, indicating that a third round was not necessary. DISCUSSION: This is the first study to differentiate between essential and redundant information in GP referral and specialist letters, and the findings could be used to improve communication between primary and secondary care.

Overall survival in EGFR mutated non-small-cell lung cancer patients treated with afatinib after EGFR TKI and resistant mechanisms upon disease progression.

PURPOSE: To determine survival in afatinib-treated patients after treatment with first-generation EGFR tyrosine kinase inhibitors (TKIs) and to study resistance mechanisms in afatinib-resistant tumors. METHODS: Characteristics and survival of patients treated with afatinib after resistance to erlotinib or gefitinib in two large Dutch centers were collected. Whole exome sequencing (WES) and pathway analysis was performed on available pre- and post-afatinib tumor biopsies and normal tissue. RESULTS: A total of 38 patients were treated with afatinib. T790M mutations were identified in 22/29 (76%) pre-afatinib treatment tumor samples. No difference in median progression-free-survival (2.8 months (95% CI 2.3-3.3) and 2.7 months (95% CI 0.9-4.6), p = 0.55) and median overall-survival (8.8 months (95% CI 4.2-13.4) and 3.6 months (95% CI 2.3-5.0), p = 0.14) were observed in T790M+ patients compared to T790M- mutations. Somatic mutations in TP53, ADAMTS2, CNN2 and multiple genes in the Wnt and PI3K-AKT pathway were observed in post-afatinib tumors of six afatinib-responding and in one non-responding patient. No new EGFR mutations were found in the post-afatinib samples of the six responding patients. Further analyses of post-afatinib progressive tumors revealed 28 resistant specific mutations in six genes (HLA-DRB1, AQP7, FAM198A, SEC31A, CNTLN, and ESX1) in three afatinib responding patients. No known EGFR-TKI resistant-associated copy number gains were acquired in the post-afatinib samples. CONCLUSION: No differences in survival were observed in patients with EGFR-T790M treated with afatinib compared to those without T790M. Tumors from patients who had progressive disease during afatinib treatment were enriched for mutations in genes involved in Wnt and PI3K-AKT pathways.

A randomized controlled trial comparing indwelling pleural catheters with talc pleurodesis (NVALT-14).

BACKGROUND: Symptomatic malignant pleural effusion (MPE) occurs frequently in patients with metastatic cancer. The associated prognosis is poor and the success rate of talc pleurodesis (TP) is low. Indwelling pleural catheters (IPCs) are commonly inserted when TP has been unsuccessful. METHODS: We compared talc pleurodesis with the use of an indwelling pleural catheter in patients with recurrent MPE in a multicenter randomized controlled trial (superiority design). The primary endpoint was improvement from baseline in Modified Borg Score (MBS) 6weeks after randomized treatment. Secondary endpoints were hospitalization days, re-interventions, and adverse events. RESULTS: Dyspnea improved significantly (p<0.01) after either treatment, but the magnitude of this improvement did not differ significantly between arms (median 3 and 1 for TP:IPC respectively in rest, p=0.16, (TP 13:IPC 16) and 3 and 1 during exercise, p=0.72 (TP 13:IPC 17)). There was no difference in dyspnea during exercise between TP and IPC at week 6 following treatment, while at rest TP patients (n=13) reported less dyspnea than IPC patients (n=18) (median 0 vs 1, p=0.002). Compared to TP, patients with an IPC had significantly less hospital days during randomized treatment (median: 0 vs 5, p<0.0001), and total hospitalizations for all causes (median: 1.6 vs 1.0, p=0.0035). Fewer IPC patients underwent more than one re-intervention (7/45 vs 15/43, p=0.09). The mean number of re-interventions was lower following IPC (0.21 vs 0.53, p=0.05). Equal number of adverse events occurred. CONCLUSIONS: IPC was not superior in the primary endpoint, improvement of the modified Borg scale (MBS). However, IPC patients had lower hospital stay, fewer admissions and fewer re-interventions. The IPC is an effective treatment modality in patients with symptomatic malignant pleural effusion.

Transient thyrotoxicosis during nivolumab treatment.

Two patients presented with transient thyrotoxicosis within 2-4 weeks after starting treatment with nivolumab. This thyrotoxicosis turned into hypothyroidism within 6-8 weeks. Temporary treatment with a beta blocker may be sufficient.

[New biopsy at lung cancer progression: rational treatment of resistant lung cancer]. / Opnieuw biopteren bij progressie van longkanker.

Nowadays, patients with advanced non-small cell lung cancer harbouring a driver mutation undergo targeted treatment. This results in profound tumour responses but inevitably induces resistance after approximately 9 to 12 months. In this article we consider the importance and clinical implications of taking new biopsies to retrieve information regarding resistance mechanisms. There is a shift in the use of other modalities such as radiotherapy and surgery in patients with oligometastatic disease, producing long-lasting responses. This is illustrated by three different patient cases: one with an EGFR exon 21 mutation, obtaining a T790M mutation upon treatment; another with a BRAF V600 mutation initially treated with chemotherapy and later with targeted therapy; and, finally, a patient with an ALK translocation with progression on crizotinib treatment, responding to subsequent alectinib therapy. The latter developed oligometastatic disease that was treated with radiotherapy, resulting in a complete response for at least 2 years.