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

Intracranial and extracranial efficacy of lorlatinib in patients with ALK-positive non-small-cell lung cancer previously treated with second-generation ALK TKIs

Lorlatinib; Càncer de pulmó de cèl·lules no petites; ALK TKI de segona generacióLorlatinib; Cáncer de pulmón de células no pequeñas; ALK TKI de segunda generaciónLorlatinib; Non-small-cell lung cancer; Second-generation ALK TKIsBackground Lorlatinib, a potent, brain-penetrant, third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), has substantial activity against ALK-positive non-small-cell lung cancer (NSCLC). This study assessed the overall, intracranial, and extracranial efficacy of lorlatinib in ALK-positive NSCLC that progressed on second-generation ALK TKIs. Patients and methods In the ongoing phase II study (NCT01970865), patients with ALK-positive advanced NSCLC treated with ≥1 prior second-generation ALK TKI ± chemotherapy were enrolled in expansion cohorts (EXP) based on treatment history. Overall, intracranial and extracranial antitumor activity were assessed independently per modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Results Of the 139 patients with ≥1 prior second-generation ALK TKI (EXP3B-5), 28 received one prior second-generation ALK TKI (EXP3B), 65 two prior ALK TKIs (EXP4), and 46 three prior ALK TKIs (EXP5). In EXP3B-5, the objective response rate (ORR) [95% confidence intervals] was 39.6% (31.4-48.2), intracranial ORR (IC-ORR) was 56.1% (42.4-69.3), extracranial ORR (EC-ORR) was 36.7% (28.7-45.3), median duration of response (DOR) was 9.6 months [5.6-16.7; IC-DOR, 12.4 (6.0-37.1); EC-DOR, 9.7 (6.1-33.3)], median progression-free survival was 6.6 (5.4-7.4) months, and median overall survival was 20.7 months (16.1-30.3). In EXP3B, the ORR was 42.9% (24.5-62.8), the IC-ORR was 66.7% (29.9-92.5), and the EC-ORR was 32.1% (15.9-52.4). In EXP4 and EXP5, the ORR was 38.7% (29.6-48.5), the IC-ORR was 54.2% (39.2-68.6), and the EC-ORR was 37.8% (28.8-47.5). Conclusions Lorlatinib had clinically meaningful intracranial and extracranial antitumor activity in the post-second-generation ALK TKI setting, with elevated intracranial versus extracranial ORR, particularly in patients with fewer lines of therapy.This work was supported by Pfizer Inc. (no grant number)

Hospital admissions and deaths relating to deliberate self-harm and accidents within 5 years of a cancer diagnosis: a national study in Scotland, UK

The risk of suicide in cancer patients has been reported as elevated in several countries. These patients are exposed to many medicines that may confuse or provide a means for harm, potentially also increasing their risk from accidents. Ratios of observed/expected numbers of hospital admission and death events relating to deliberate self-harm (DSH) and accidents were calculated in the 5 years from a cancer diagnosis in Scotland 1981–1995, compared to the matched general population. The relative risk (RR) of suicide was 1.51 (95% confidence interval (CI): 1.29–1.76). The RR of hospital admissions for DSH was not significantly increased, suggesting a strong suicidal intent in DSH acts in cancer patients. Accidental poisonings and all other accidents were both increased (RR death=3.69, 95% CI: 2.10–6.00; and 1.58, 95% CI: 1.48–1.69, respectively) (RR hospital admissions=1.32, 95% CI: 1.19–1.47; and 1.55, 95% CI: 1.53–1.57, respectively). The association of only certain tumour types (e.g. respiratory) with suicide and accidental poisoning, and a broad range of tumour types with an elevated risk of all other accidents, suggests accidental poisoning categories may be a common destination for code shifting of some DSH events. A previous history of DSH or accidents, significantly increased the RR of suicide or fatal accidents, respectively (RR suicide=14.86 (95% CI: 4.69–34.97) vs 1.16 (95% CI: 0.84–1.55)) (RR accidental death=3.37 (95% CI: 2.53–4.41) vs 1.29 (95% CI: 1.12–1.49)). Within 5 years of a cancer diagnosis, Scottish patients are at increased RR of suicide and fatal accidents, and increased RR of hospital admissions for accidents. Some of these accidents, particularly accidental poisonings, may contain hidden deliberate acts. Previous DSH or accidents are potential markers for those most at risk, in whom to target interventional techniques

Women with a low satiety phenotype show impaired appetite control and greater resistance to weight loss.

AbstractThis trial compared weight loss outcomes over 14-weeks in women showing low or high satiety responsiveness [low or high satiety phenotype (LSP, HSP)] measured by a standardized protocol. Food preferences and energy intake after low and high energy density (LED, HED) meals were also assessed. Ninety-six women (n = 52 analysed; 41.24 ± 12.54 years; 34.02 ± 3.58 kg/m2) engaged in one of two weight loss programs underwent LED and HED laboratory-test days during weeks 3 and 12. Preferences for LED and HED-foods (Leeds Food Preference Questionnaire) and ad libitum evening meal and snack energy intake (EI) were assessed in response to equi-caloric LED- and HED-breakfasts and lunches. Weekly questionnaires assessed control over eating and ease of adherence to the program. Satiety quotients based on subjective fullness ratings post-LED and HED breakfasts determined LSP (n=26) and HSP (n=26) by tertile splits. Results showed that the LSP lost less weight and had smaller reductions in waist circumference compared to HSP. The LSP showed greater preferences for HED-foods, and under HED-conditions, consumed more snacks (kcal) compared to HSP. Snack EI did not differ under LED-conditions. LSP reported less control over eating and reported more difficulty with program adherence. In conclusion, low satiety responsiveness is detrimental for weight loss. LED meals can improve self-regulation of EI in the LSP, which may be beneficial for longer-term weight control.</jats:p