Phase Ib study of telisotuzumab vedotin in combination with erlotinib in patients with c-Met protein-expressing non-small-cell lung cancer

PURPOSE: Overexpression of c-Met protein and epidermal growth factor receptor ( PATIENTS AND METHODS: This study evaluated Teliso-V (2.7 mg/kg once every 21 days) plus erlotinib (150 mg once daily) in adult patients (age ≥ 18 years) with c-Met+ NSCLC. Later enrollment required presence of an RESULTS: As of January 2020, 42 patients were enrolled (N = 36 efficacy-evaluable). Neuropathies were the most common any-grade adverse events reported, with 24 of 42 patients (57%) experiencing at least one event. The pharmacokinetic profile of Teliso-V plus erlotinib was similar to Teliso-V monotherapy. Median PFS for all efficacy-evaluable patients was 5.9 months (95% CI, 2.8 to not reached). ORR for CONCLUSION: Teliso-V plus erlotinib showed encouraging antitumor activity and acceptable toxicity in EGFR TKI-pretreated patients wit

PD-1/PD-L1 inhibitor activity in patients with gene-rearrangement positive non-small cell lung cancer-an IMMUNOTARGET case series.

BACKGROUND Prior IMMUNOTARGET registry data had suggested that responses to immune [anti PD(L)1] monotherapy in gene-arranged non-small cell lung cancer (NSCLC) were rare or absent, depending on the specific oncogene. METHODS IMMUNOTARGET sites reporting prior registry data or new individual cases of gene rearranged NSCLC seeming to benefit from immune monotherapy were explored in detail looking to both validate their diagnosis of a functional gene rearrangement and to look for features potentially differentiating them from other such cases associated with low response rates. RESULTS Five cases of NSCLC with a gene rearrangement with reported responses or prolonged stabilization from immune monotherapy were identified in total. All had little or no prior smoking history and had programmed death-ligand 1 (PD-L1) values ranging from zero to 100%. A confirmed rearrangement partner was reported in only 2 of the cases (CD74-ROS1 and KIF5B-RET), however in one of the other three cases [analplastic lymophoma kinase (ALK)], significant benefit from a relevant prior targeted therapy was noted, also consistent with the rearrangement status being correctly assigned. CONCLUSIONS Not all driver oncogene subtypes of NSCLC are equally responsive to immune monotherapy, however even among patients with well-validated gene rearranged NSCLC which has traditionally been considered immune hyporesponsive, objective responses can occur. Additional explorations of the features associated with and underlying the immune hypo-responsiveness of most, but not all, cases of gene-rearranged NSCLC are required

The patient experience with shared decision-making in lung cancer: A survey of patients, significant others or care givers

A survey (via SurveyMonkey) was sent to lung cancer patients, their caregivers or significant others asking about their experience in making difficult treatment decisions. Of the 198 respondents, 118 (69%) indicated that they had faced a difficult decision with respect to their lung cancer treatment. Of those, 73% indicated that they would have desired that the decision be made with their physician using a shared decision-making process, and 58% perceived that such a process had occurred. In addition, only 23% of respondents indicated that they had had the right amount of information when making the decision. Fortunately, only 9% of respondents expressed regret regarding the decision they ultimately made. A Patient Decision Aid (PDA) was made available to the respondents to view, and opinions were sought regarding the usefulness of this type of format for presenting information. This format was perceived as helpful, unsure if helpful, or not helpful by 62%, 36%, and 2% of respondents, respectively. In summary, the majority of lung cancer patients want to make difficult decisions using a shared decision-making process. The patient perception is that this is not occurring often enough. Even in this fairly well-educated group of respondents, many report that they are not sure that they have all the information necessary to make that difficult decision. Physicians may need help developing their communication and shared decision-making skills. Introducing PDAs into the oncology clinic may represent a way to present complex information and improve the patient experience

A Changing of the Guard: Immune Checkpoint Inhibitors With and Without Chemotherapy as First Line Treatment for Metastatic Non-small Cell Lung Cancer

Inhibitory antibodies targeting programmed death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) have resulted in improved outcomes for many patients with metastatic non-small cell lung cancer in (NSCLC) in the second-line setting due to their ability to lead to prolonged anti-tumor immune responses. Combining these immunotherapies with platinum-based chemotherapy as first-line treatment has resulted in improved response rates and increased survival when compared to platinum-based chemotherapy alone. Certain patient populations may even benefit from immune checkpoint inhibitors as monotherapy in the first-line setting. The PD-1 inhibitor pembrolizumab is approved as monotherapy or in combination with platinum + pemetrexed for most newly diagnosed patients with metastatic NSCLC, excluding those with a targetable oncogene such as ALK and EGFR. The PD-L1 inhibitor atezolizumab is also approved in combination with bevacizumab + carboplatin + paclitaxel for the same population, with some parts of the world also approving this regimen for patients with ALK rearrangements or EGFR activating mutations. However, there are many other chemo-immunotherapy regimens that have been evaluated as initial treatment in metastatic NSCLC. Additionally, combinations of PD-1 axis inhibitors with cytotoxic T lymphocyte antigen-4 inhibitors have been examined, although none are yet approved. Here we review the clinical data in support of the current first-line approaches across histologies and biomarker subtypes, as well as highlight future research directions revealed by the current data

Brigatinib Versus Crizotinib in ALK Inhibitor–Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial

ALK tyrosine kinase inhibitor; Brigatinib; Non–small cell lung cancerInhibidor de la tirosina quinasa ALK; Brigatinib; Cáncer de pulmón de células no pequeñasInhibidor de la tirosina cinasa ALK; Brigatinib; Càncer de pulmó de cèl·lules no petitesIntroduction In the phase 3 study entitled ALK in Lung cancer Trial of brigAtinib in 1st Line (ALTA-1L), which is a study of brigatinib in ALK inhibitor–naive advanced ALK-positive NSCLC, brigatinib exhibited superior progression-free survival (PFS) versus crizotinib in the two planned interim analyses. Here, we report the final efficacy, safety, and exploratory results. Methods Patients were randomized to brigatinib 180 mg once daily (7-d lead-in at 90 mg once daily) or crizotinib 250 mg twice daily. The primary end point was a blinded independent review committee–assessed PFS. Genetic alterations in plasma cell-free DNA were assessed in relation to clinical efficacy. Results A total of 275 patients were enrolled (brigatinib, n = 137; crizotinib, n = 138). At study end, (brigatinib median follow-up = 40.4 mo), the 3-year PFS by blinded independent review committee was 43% (brigatinib) versus 19% (crizotinib; median = 24.0 versus 11.1 mo, hazard ratio [HR] = 0.48, 95% confidence interval [CI]: 0.35–0.66). The median overall survival was not reached in either group (HR = 0.81, 95% CI: 0.53–1.22). Posthoc analyses suggested an overall survival benefit for brigatinib in patients with baseline brain metastases (HR = 0.43, 95% CI: 0.21–0.89). Detectable baseline EML4-ALK fusion variant 3 and TP53 mutation in plasma were associated with poor PFS. Brigatinib exhibited superior efficacy compared with crizotinib regardless of EML4-ALK variant and TP53 mutation. Emerging secondary ALK mutations were rare in patients progressing on brigatinib. No new safety signals were observed. Conclusions In the ALTA-1L final analysis, with longer follow-up, brigatinib continued to exhibit superior efficacy and tolerability versus crizotinib in patients with or without poor prognostic biomarkers. The suggested survival benefit with brigatinib in patients with brain metastases warrants future study

A phase 1 study evaluating rovalpituzumab tesirine in frontline treatment of patients with extensive-stage SCLC

INTRODUCTION: Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate targeting DLL3, a Notch pathway ligand highly expressed on SCLC cells. Rova-T was evaluated alone or in combination with platinum-based chemotherapy (cisplatin or carboplatin combined with etoposide [CE]) in frontline treatment of extensive-stage SCLC. METHODS: One cycle of CE pre-enrollment was permitted (later mandated). The following four cohorts were enrolled: Rova-T monotherapy (0.3 mg/kg, every 6 [q6] wk × 2; cohort 1; n = 4); Rova-T induction (0.3 mg/kg, q6 wk × 2) followed by CE every 21 days (q21) × 4 (cohort 2; n = 5); Rova-T (0.1 or 0.2 mg/kg, q6 wk × 2) overlapping with CE q21 × 4 (cohort 3; n = 14); and Rova-T maintenance (0.3 mg/kg, q6 wk × 2) after CE q21 × 4 (cohort 4; n = 3). RESULTS: A total of 26 patients were dosed (cohort 3: 14; cohorts 1, 2, and 4 combined: 12). Median age was 66 years, and 73% had Eastern Cooperative Oncology Group performance status of 1. In cohort 3, seven patients (50%) had confirmed objective responses, with a median progression-free survival of 5.2 months and median overall survival of 10.3 months. Compared with cohorts 1, 2, and 4 combined, cohort 3 had lower frequency of some Rova-T-related adverse events of special interest, such as pleural effusion (0 versus 33%), pericardial effusion (0 versus 17%), ascites (0 versus 8%), peripheral edema (36% versus 42%), generalized edema (0 versus 8%), pneumonia (7% versus 25%), and hypoalbuminemia (0 versus 17%). CONCLUSIONS: Lower Rova-T doses may be associated with lower incidence of some Rova-T-related adverse events of special interest. Rova-T 0.2 mg/kg plus CE (cohort 3) was tolerable; however, there was no clear efficacy benefit of adding Rova-T to CE

Updates in the management of brain metastases

The clinical management/understanding of brain metastases (BM) has changed substantially in the last 5 years, with key advances and clinical trials highlighted in this review. Several of these changes stem from improvements in systemic therapy, which have led to better systemic control and longer overall patient survival, associated with increased time at risk for developing BM. Development of systemic therapies capable of preventing BM and controlling both intracranial and extracranial disease once BM are diagnosed is paramount. The increase in use of stereotactic radiosurgery alone for many patients with multiple BM is an outgrowth of the desire to employ treatments focused on local control while minimizing cognitive effects associated with whole brain radiotherapy. Complications from BM and their treatment must be considered in comprehensive patient management, especially with greater awareness that the majority of patients do not die from their BM. Being aware of significant heterogeneity in prognosis and therapeutic options for patients with BM is crucial for appropriate management, with greater attention to developing individual patient treatment plans based on predicted outcomes; in this context, recent prognostic models of survival have been extensively revised to incorporate molecular markers unique to different primary cancers