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Introduction Cabazitaxel multiple rechallenges may be a treatment option in heavily pretreated patients with metastatic castration‐resistant prostate cancer (mCRPC) who had a good initial response to cabazitaxel and who are still fit to receive it. Our objective was to assess the efficacy and toxicity of multiple rechallenges. Patients and methods We retrospectively identified 22 mCRPC patients previously treated with docetaxel and/or androgen receptor‐targeted agents who received multiple cabazitaxel rechallenges in 9 French centers. Cabazitaxel was initiated at a dose of 25 mg/m2 q3week. A reduced dose (20 mg/m2 q3w) or an alternative schedule (mainly 16 mg/m2 q2w) was increasingly used for subsequent rechallenges. Progression‐free survival, prostate‐specific antigen (PSA) response, best clinical response, and grade ≥3 toxicities were collected. Overall survival was calculated from various time points. Results Twenty‐two patients with an initial response to cabazitaxel were rechallenged at least twice. The median number of cabazitaxel cycles was 7 at first cabazitaxel treatment, 6 at first rechallenge, and 5 at subsequent rechallenges. Median progression‐free survival at first rechallenge was 9.6 months and 5.6 months at second rechallenge. Median overall survival was 50.9 months from the first cabazitaxel dose, 114.9 months from first life‐extending therapy initiation in mCRPC, and 105 months from mCRPC diagnosis. There was no cumulative grade ≥3 neuropathy or nail disorder and one case of febrile neutropenia. Conclusion Cabazitaxel multiple rechallenges may be a treatment option without cumulative toxicity in heavily pretreated patients having a good response to first cabazitaxel use and still fit to receive it. Novelty & Impact Statements Patients with metastatic castration‐resistant prostate cancer can be treated with Cabazitaxel after docetaxel and androgen receptor‐targeted agent. This chemotherapy can be used multiple times with efficacy and manageable toxicity., We assessed the efficacy and toxicity of multiple rechallenges with cabazitaxel for 22 patients with metastatic castration‐resistant prostate cancer (mCRPC). Median overall survival was 50.9 months from the first cabazitaxel dose, 114.9 months from first life‐extending therapy initiation in mCRPC, and 105 months from mCRPC diagnosis. Cabazitaxel rechallenge may be an effective option in heavily pretreated mCRPC patients with a good initial response to cabazitaxel and still fit to receive it, without cumulative grade ≥3 toxicity.

New anti-cancer therapeutics have been developed in the recent years and dramatically change prognosis and patient management. Either used alone or in combination, immune checkpoint inhibitors (ICI), such as anti-CTLA-4 and anti-PD1/PD-(L)1, act by removing T-cell inhibition to enhance their antitumor response. This change in therapeutic targets leads to a break in immune-tolerance and a unique toxicity profile resulting in immune complications. These side effects, called Immune-Related Adverse Events (IrAEs), can affect all organs, with a wide range of clinical and biological presentations and severity. Various rheumatic and musculoskeletal manifestations have been reported in the literature, ranging from mild arthralgia, polymyalgia rheumatica, to genuine serodefined rheumatoid arthritis and myositis. Tolerance studies suggest some correlations between IrAEs occurrence and tumor response. Assessment of patient musculoskeletal status prior to the start of the ICI is warranted. Management of rheumatic IrAEs does not usually request ICI discontinuation, exception for myositis or very severe forms where it should be discussed. Treatment relies on non-steroidal anti-inflammatory drugs (NSAIDs) or low dose glucocortioids (

The impact of immune-related adverse events (irAE) on survival outcomes after single-agent immune checkpoint inhibitors (ICIs) remains unclear. We aimed to evaluate the association between irAEs and ICI efficacy in various malignancies.All patients treated with a single-agent ICI for any advanced cancer were included in this retrospective multicentric series. The primary objective was to assess the impact of all type grade ≥II irAEs on progression-free survival (PFS) and overall survival (OS). IrAEs were first considered as a fixed covariate and included in Cox-regression models. In addition, as irAEs are time-related events and can occur at any point during follow-up, we analysed the occurrence of irAEs as a time-varying covariate.In this cohort of 410 patients, the majority of patients (70%) were treated for non-small cell lung cancer. The ICI was an anti-PD(L)1 for 356 patients (82%) and an anti-CTLA4 for 79 patients (18%). In total 126 (29%) of the patients presented at least one grade ≥II irAEs. The first occurrence of a grade ≥II irAE had a positive impact on PFS and OS when considered as a fixed or as a time-varying covariate (hazard ratio [HR] for PFS = 0.63, 95% confidence interval [CI] 0.50-0.81; P = 0.00022; HR for OS = 0.57, 95% CI 0.43-0.74, P 0.0001). This overall finding was confirmed in patients treated with an anti-PD(L)1 and among patients with lung cancer.In this pooled multi-institutional cohort, the incidence of irAEs was associated with better long-term survival across different malignancies treated with ICI monotherapy.

The immune checkpoint inhibitors (CPI) such as anti-PD(L)1 or anti-CTLA4 had improved long-term patients' outcomes in different malignancies. Thyroid disorders are the most frequent endocrine side effects from CPI reported in clinical trials and in clinical routine practice. The incidence of thyroid dysfunction is variable according to ICP used (more frequent under anti-programmed cell death 1 (PD1) or anti-programmed cell death-ligand 1 (PDL1)). Most thyroid dysfunctions have been reported to occur 2 to 4 courses after CPI initiation. The clinical symptoms are generally nonspecific (asthenia, weight change, rarely cardiac rhythm disorder). These thyroid dysfunctions are commonly painless thyroiditis with a biphasic evolution: thyrotoxicosis followed by a secondary hypothyroidism frequently definitive. Diagnosis is made on a thyroid test (TSH and FT4). In most cases, no further exam is necessary. Beta blockers therapy is recommended in symptomatic thyrotoxicosis with palpitations. Thyroid hormones therapy will be introduced quickly in case of hypothyroidism. Thyroid dysfunctions are not a contra-indication to the continuation of immunotherapy. Due to the high frequency of these complications, close monitoring of the thyroid status is recommended under CPI.

Platinum-based chemotherapy is commonly associated with toxic sensory neuropathies, but also, although rarely, with Guillain-Barré syndrome (GBS). We describe five patients who developed GBS while receiving platinum-based chemotherapy for a solid tumor and report the five cases published so far. Most patients had received cumulative platinum doses below known neurotoxic levels, and all of them had an optimal outcome after platinum discontinuation, associated in most cases with administration of intravenous immunoglobulin. Clinical presentation, electroneuromyography, and cerebrospinal fluid analysis help clinicians to differentiate GBS from toxic neuropathy. Platinum compounds are the only chemotherapeutic agents used for solid tumors that have been associated to GBS. Thus, we propose that GBS may constitute a non–dose-dependent side effect of platinum drugs and that awareness needs to be raised among oncologists on this rare but potentially life-threatening complication of platinum chemotherapy. Implications for Practice: Many patients on platinum-based chemotherapy for solid tumors develop sensory neuropathy, a common dose-dependent side effect. The authors propose that Guillain-Barré syndrome may constitute an immune-mediated, non-dose-related side effect of platinum-based chemotherapy. Prompt diagnosis of Guillain-Barré syndrome and distinction from classical toxic neuropathy are crucial for optimal treatment. Platinum discontinuation, associated if needed to intravenous immunoglobulin administration, radically changes the course of the disease and minimizes neurological sequelae.

[Background] There are limited data on toxicity and surgical safety associated with neoadjuvant programmed death ligand 1 (PD-L1) inhibitors prior to radical cystectomy (RC) in patients with muscle-invasive bladder cancer (MIBC)., [Objective] To present a comprehensive safety analysis of the largest neoadjuvant series, with focus on timing and severity of toxicity and surgical complications occurring after neoadjuvant atezolizumab in patients with MIBC enrolled in the ABACUS trial., [Design, setting, and participants] ABACUS (NCT02662309) is an open-label, multicenter, phase II trial for patients with histologically confirmed (T2-T4aN0M0) MIBC, awaiting RC. Patients either were ineligible or refused cisplatin-based neoadjuvant chemotherapy., [Intervention] Two cycles of neoadjuvant atezolizumab (1200 mg, every 3 wk) followed by RC., [Outcome measurements and statistical analysis] Description of atezolizumab toxicity profile in the neoadjuvant setting, impact on surgery, and delayed immune-mediated adverse events (AEs) were assessed., [Results and limitations] Ninety-five patients received treatment. Of them, 44% (42/95) had atezolizumab-related AEs during the neoadjuvant period (fatigue [20%], decreased appetite [6%], and transaminases increased [6%]). Treatment-related grade 3–5 AEs occurred in 11% (10/95) of patients during the study. Of the patients, 21% (20/95) received only one cycle of atezolizumab due to AEs; 92% (87/95) underwent RC. No surgery was delayed due to atezolizumab-related toxicities. Surgical complications occurred in 62% (54/87) of patients. Of these patients, 43% (37/87) and 20% (17/87) had minor (grade 1–2) and major (grade 3–5) complications, respectively. Thirteen of 87 (15%) patients had post-RC atezolizumab-related AEs, including adrenal insufficiency and transaminases increased. Three deaths occurred during the period of study-related interventions (one non–treatment-related aspiration pneumonia, one immune-related myocardial infarction, and one cardiogenic shock after RC). Not all surgical safety parameters were available., [Conclusions] Two cycles of neoadjuvant atezolizumab are well tolerated and do not seem to impact surgical complication rates. Owing to the long half-life, AEs may occur in the postoperative period, including endocrine abnormalities requiring attention and intervention., [Patient summary] Here, we report a comprehensive dataset of patients receiving neoadjuvant immune checkpoint inhibitors before radical cystectomy. Treatment with neoadjuvant atezolizumab is safe and does not seem to complicate surgery significantly., Queen Mary University of London was the Sponsor of the study. Roche granted QMUL funding for the study. J. Bull and M. Jacobson also provided financial support for aspects of the biomarker analysis. We acknowledge Cancer Research UK, the UK Experimental Cancer Medicine Network, and La Roche-Hoffmann for funding.

Acute Kidney Injury (AKI), induced by Checkpoint Inhibitors therapies (CPI-induced AKI), is an uncommon but severe Immune-Related Adverse Event (IRAE). The aim was to describe the epidemiology, risks factors, clinical, and laboratory characteristics of these renal adverse events (AEs) in a real-life cohort treatment.Consecutive patients undergoing a checkpoint inhibitor (CPI) therapy at the Hôpital Lyon Sud from January 2015 to July 2017 were included. A systematic retrospective analysis of medical files was performed, monthly serum creatinine levels, associated treatments, and occurrence of other IRAEs data were collected. AKI episodes explained by classic AKI aetiologies (prerenal, obstructive, septic) were excluded from the analysis.CPI-induced AKI incidence was 3.7% (13/352) and appeared to be time-dependent (7.7% (11/143) for patients with3 months of CPI exposure), ranging from 1 to 16 months. All cases with available histology were acute tubulointerstitial nephritis (ATIN), with poor urinary sediment. The severity of AKI was mild (stage 1 in 50% of cases), with no need for renal-replacement therapy. Although CPI-induced AKI patients had more frequently other IRAEs (77% versus 39%), this was not associated with a greater risk of AKI. Pre-existing chronic kidney disease (defined as an estimated glomerular filtration rate (eGFR)60 ml/min) was not associated with a greater risk of CPI-induced AKI. Treatments of CPI-induced AKI were heterogeneous, with discontinuation of CPIs, and inconstant systemic corticosteroid therapy.The monitoring of renal function and early identification of AKI during CPIs treatment is essential. The optimal management of CPI-induced AKI remains unclear and requires a close collaboration between the oncology and nephrology departments.Immune checkpoint inhibitors (CPIs) have dramatically improved patient outcomes in different malignant contexts such as melanoma, non-small cell lung cancers (NSCLC) and urologic cancers. Usually well-tolerated, CPIs are however associated with immune-related adverse events (IRAEs). Among them, acute kidney injury (AKI) is uncommon, and not well-described. Following the exponential increase in the prescription of CPIs, previously uncommon cases of IRAEs (such as AKI) have become common occurrence in referral centres. Data regarding the epidemiology, risk factors, or management of CPI-induced AKI are currently lacking or can be discordant. Data regarding CPI-induced AKI, in a large real-life cohort were reported herein.

The advent of immune checkpoint-inhibitors (CPI) has transformed treatment for several cancer types. This review was performed to assess the rate of adverse events (AEs) associated with the use of CPI, alone or in combinations. A review of AEs reporting quality was also performed. All publications of Randomized Clinical Trials (RCTs) assessing CPI published before December 2017 were included. To investigate the quality of AEs reporting, a set of items was defined based on the 2004 CONSORT harms extension statement. Rates of Grade 5, serious, and study-withdrawal related AEs were collected in each treatment category. Specific immune related AEs (irAEs) were also collected when available. Pooled estimates of adverse event rates were calculated by using generalized linear mixed model. A total of 35 RCTs including 16,485 patients were included. The overall quality of AEs reporting was satisfactory, but items pertaining to methods of data collection and analysis were infrequently reported. Grade ≥ 3 AEs were reported for 14% (95% CI 12-16) of patients treated with PD(L)-1 inhibitors, 34% (95% CI 27-42) of patients treated with CTLA-4 inhibitors, 55% (95% CI 51-59) of patients on CPI combinations and 46% (95% CI 40-53) of patients on immunotherapy-chemotherapy combination. The profile of irAEs was different among the treatment categories. The use of CPI, especially in combination, is associated with significant rates of Grade ≥ 3 AEs. Healthcare planning should anticipate the expected high number of patients presenting with irAEs in the future.

The majority of patients with prostate cancer who later develop lethal metastatic disease have high-risk localized disease at presentation, emphasizing the importance of effective treatment strategies at this stage. Multimodal treatment approaches that combine systemic and local therapies offer a promising strategy for improving the clinical outcomes of patients with high-risk localized prostate cancer. Combinations of neoadjuvant and adjuvant chemotherapy, hormonal therapy, or chemohormonal therapy are considered to be the standard of care in most solid tumours and should be investigated in the future for the treatment of prostate cancer to improve patient outcomes. However, although the combination of androgen deprivation therapy and radiotherapy is a standard of care in high-risk localized or locally advanced prostate cancer, the benefit of chemotherapy or chemohormonal therapy has yet to be demonstrated outside of the metastatic setting. Moreover, the benefit of neoadjuvant and/or adjuvant systemic therapies in combination with radical prostatectomy has not been proved. The development of next-generation hormonal agents, which have been approved for the treatment of castration-resistant prostate cancer, offers further therapeutic possibilities that are being assessed in early-phase clinical trials.

Emerging evidence from population-based and retrospective series suggests a potential improvement of clinical outcomes in metastatic prostate cancer. Moreover, metastasis-directed treatment has shown encouraging results in this setting. There is an increasing interest in exploring the potential of local therapies in advanced prostate cancer, but this has rarely been specifically addressed in the castration-resistant state, whether non-metastatic or metastatic. A review of relevant articles was performed on the oncologic benefit of local treatment of the primary tumor or metastasis-targeted treatment in castration-resistant prostate cancer patients. The main goal of this strategy is to delay introduction of a new systemic agent to maintain quality of life and potentially to limit resistance. Further investigation is required to provide high-level evidence for the oncologic benefit of this treatment modality.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Resume Les indications des inhibiteurs de checkpoint (ICP) immunitaire sont maintenant tres etendues et ont fait emerger des complications endocriniennes specifiques avec lesquelles les oncologues ont du se familiariser. L’hypophysite en est un exemple typique, devenue une complication non rare des ICPs, touchant jusqu’a 10 % des patients traites par anti-CTLA4. Elle survient classiquement deux a trois mois apres l’initiation du traitement. Le tableau associe typiquement cephalees et alteration de l’etat general, associees a une hyponatremie. Les atteintes hormonales les plus frequentes touchent les secteurs thyreotropes, gonadotrope et corticotrope. L’atteinte corticotrope fait la gravite de cette pathologie, necessitant la mise en place urgente d’une supplementation, sans attendre la confirmation biologique dans les cas severes. L’IRM doit etre systematiquement realisee, essentiellement pour eliminer les diagnostics differentiels, dont les metastases hypophysaires. L’hypophysite induite par les ICPs de type anti-PD1/PDL1 est une entite a part, de survenue retardee, pauci-symptomatique, mais caracterisee par une insuffisance corticotrope systematique et definitive, le plus souvent isolee au vu des premieres donnees publiees. Le traitement repose sur la corticotherapie a forte dose uniquement en cas de cephalees resistantes ou d’insuffisance corticotrope decompensee, et sur la supplementation hormonale systematique des deficits antehypophysaires. Les patients necessiteront une supplementation hormonale a vie, et doivent etre pris en charge et eduques en endocrinologie. Une fois l’episode aigu resolu, l’immunotherapie peut etre poursuivie si le patient en a un benefice. Compte tenu du caractere peu symptomatique et de la gravite potentielle de ces hypophysites, une surveillance biologique systematique est necessaire pendant le traitement par ICPs.

Antibodies targeting PD-1 or its ligand 1 PD-L1 such as atezolizumab, have great efficacy in a proportion of metastatic urothelial cancers1,2. Biomarkers may facilitate identification of these responding tumors3. Neoadjuvant use of these agents is associated with pathological complete response in a spectrum of tumors, including urothelial cancer4-7. Sequential tissue sampling from these studies allowed for detailed on-treatment biomarker analysis. Here, we present a single-arm phase 2 study, investigating two cycles of atezolizumab before cystectomy in 95 patients with muscle-invasive urothelial cancer (ClinicalTrials. gov identifier: NCT02662309). Pathological complete response was the primary endpoint. Secondary endpoints focused on safety, relapse-free survival and biomarker analysis. The pathological complete response rate was 31% (95% confidence interval: 21-41%), achieving the primary efficacy endpoint. Baseline biomarkers showed that the presence of preexisting activated T cells was more prominent than expected and correlated with outcome. Other established biomarkers, such as tumor mutational burden, did not predict outcome, differentiating this from the metastatic setting. Dynamic changes to gene expression signatures and protein biomarkers occurred with therapy, whereas changes in DNA alterations with treatment were uncommon. Responding tumors showed predominant expression of genes related to tissue repair after treatment, making tumor biomarker interpretation challenging in this group. Stromal factors such as transforming growth factor-beta and fibroblast activation protein were linked to resistance, as was high expression of cell cycle gene signatures after treatment.

Background Determining the optimal biological dose (OBD) has been described as an alternative strategy to the maximum tolerated doses (MTDs) for identifying the recommended phase II trial doses (RP2Ds) of phase I anti-cancer therapies. However, the clinical relevance is still unknown. An extensive review was performed to assess if the OBDs defined in early-phase trials were useful for subsequent drug development and approvals. Methods All the molecular targeted therapies approved by the Food and Drug Administration (FDA) in solid oncology or in haematological malignancies before July 2018 were listed through the National Cancer Institute Database. The early-phase trial publications investigating these drugs as single agents were retrieved and analysed to identify the drugs for which OBDs were reported. The publications of subsequent pivotal efficacy clinical trials leading to the approvals were retrieved, and OBDs compared with the final labelled doses and dosing schedules. Results A total of 87 early-phase trial publications were analysed, corresponding to 81 FDA-approved targeted therapies. OBDs were reported for 40% (32/81) of these drugs (19 small molecules, 13 monoclonal antibodies). MTDs were not identified for 59% (19/32) of molecules. When the OBDs were selected as the RP2Ds (18/32 molecules), the final FDA-approved doses were consistent with the OBDs for 83% of the drugs, which is much higher than the previously reported 58% rate when MTDs were chosen as the RP2Ds. Conclusion Although still poorly investigated, the OBD may be a relevant and complementary end-point for early-phase trials of targeted therapies.

Background In metastatic castration-resistant prostate cancer (mCRPC), androgen receptor splice variant 7 (AR-V7) expression is associated with a low response to androgen receptor signaling (ARS) inhibitors such as abiraterone or enzalutamide. Objective To perform a highly sensitive assay for detecting AR-V7 (hsAR-V7) in circulating tumor cells (CTCs) and evaluate its ability to predict response to ARS inhibitors. Design, setting, and participants From 41 mCRPC patients, CTCs were prospectively enriched using AdnaTest platform and analyzed for AR-V7 with and without the highly sensitive assay. Outcome measurements and statistical analysis The first objective of the study was to compare AR-V7 detection rates with and without the highly sensitive assay. Next, we investigated how AR-V7 (detected without the highly sensitive assay) and hsAR-V7 status influenced prostate-specific antigen (PSA) response and long-term clinical outcomes (PSA progression-free survival [PFS] and radiological PFS) after ARS-inhibitor treatment. Finally, discriminatory abilities of the assays were assessed by C-index to compare their impact on long-term clinical outcomes. Results and limitations AR-V7 detection rates increased from 22% to 56% when the highly sensitive assay was used. The discriminatory abilities of hsAR-V7 for PSA PFS (C-index, 0.74; 95% confidence interval [CI], 0.60–0.88) and radiological PFS (0.70; 95% CI, 0.55–0.85) were higher than those of AR-V7 detected without the highly sensitive assay (0.60, 0.51–0.72, and 0.56, 0.44–0.67, respectively). After ARS-inhibitor treatment, PSA response was lower in hsAR-V7+ (53%) than in hsAR-V7– (93%) patients (p = 0.016). AR-V7+ patients had shorter median PSA PFS (3.0 vs 10.6 mo, p = 0.032) and nonsignificantly shorter median radiological PFS (6.0 vs 14.8 mo, p = 0.24) compared with AR-V7– patients. The hsAR-V7+ status was associated with shorter median PSA PFS (3.0 mo vs not reached, p = 0.0001) and radiological PFS (median, 6.0 mo vs not reached, p = 0.0026). Conclusions The hsAR-V7 assay achieved the highest AR-V7 detection rates among those reported in mCRPC. Discriminatory abilities for long-term clinical outcomes were better with hsAR-V7 assay. Patient summary We prospectively analyzed circulating tumor cells from men with metastatic castration-resistant prostate cancer for androgen receptor splice variant 7 (AR-V7) status using a highly sensitive assay. It yielded higher AR-V7 detection rates and predicted resistance to androgen receptor signaling inhibitors with better discriminatory abilities for long-term clinical outcomes.

International audience

It remains unclear whether immune-related adverse events (irAEs) and glucocorticoid use could impact long-term outcomes in patients treated for solid tumors with immune checkpoint inhibitors (ICI). All patients treated with a single-agent ICI for any advanced cancer were included in this retrospective unicentric study. The objectives were to assess the impact of grade ≥3 irAEs, glucocorticoid use and the interruption of immunotherapy on progression-free survival (PFS) and overall survival (OS). In this 828-patient cohort, the first occurrence of grade ≥3 irAEs had no significant impact on PFS or OS. Glucocorticoid administration for the irAEs was associated with a significantly shorter PFS (adjusted HR 3.0, p = 0.00040) and a trend toward shorter OS. ICI interruption was associated with a significantly shorter PFS (adjusted HR 3.5, p &lt, 0.00043) and shorter OS (HR 4.5, p = 0.0027). Glucocorticoid administration and ICI interruption were correlated. In our population of patients treated with single agent ICI, grade ≥3 irAEs did not impact long-term outcomes. However, the need for glucocorticoids and the interruption of immunotherapy resulted in poorer long-term outcomes. The impact of grade ≥3 irAEs reported in other studies might then be explained by the management of the irAEs.

97 Background: Cabazitaxel rechallenge could be a more efficient therapy with an acceptable toxicity than docetaxel in the treatment of patients with a metastatic castration resistant prostate cancer (mCRPC). The aim of this study was to assess the feasibility and efficacy of cabazitaxel multiple rechallenge. Methods: This is a multicenter, retrospective cohort study including patients from 9 centers in France who received 3 lines or more of cabazitaxel from February 2012 to July 2020. Cabazitaxel schedule differed between patients: 25 mg/m2 q3w, 20 mg/m2 q3w, 16 mg/m2 q2w or 10 mg/m2 weekly. Efficacy was assessed by overall survival (OS) and progression-free survival (PFS) from each cabazitaxel line start. Only toxicities grade ≥ 3 were reported. Results: Twenty-two patients were included. The median follow-up from mCRPC was 94.7 months, median age at initial diagnosis was 59.5 years old, median ISUP score at diagnosis was 4 and median PSA at diagnosis was 55 ng/ml. Median number of cabazitaxel cycles was 7 at first-line, 6 at first rechallenge, and 5 for subsequent rechallenges. Median OS from mCRPC diagnosis was 105 months. Median PFS from cabazitaxel line start was 11.8 months at first use, 9.6 for first rechallenge and 5.6 in second rechallenge (table). Only one case of febrile neutropenia and 6 events of grade ≥ 3 toxicity were reported. Conclusions: Cabazitaxel multiple rechallenge could efficiently extend OS with manageable toxicities for patients. Even if anti-PARP therapy and immunotherapy are promising treatments, cabazitaxel rechallenge could be also a relevant therapeutic option for long responder patients. Specific biomarkers should be explored to predict the efficacy of cabazitaxel rechallenge. [Table: see text]

Objectives: Defining the optimal doses & dosing schedules of combined targeted drugs is a challenge. Blocking both the PI3K-AKT-mTor and RAS-RAF-ERK pathways is a rationale therapeutic strategy in solid tumors. However, the phase 1 trials of everolimus (EVE) and sorafenib (SOR) failed to define the recommended phase II trial doses (RP2D) of both drugs, due to the toxicity when given continuously; and the combination was abandoned. The academic multi-parameter EVESOR trial (NCT01932177) was designed to assess alternative doses & dosing schedules of EVE & SOR, and to provide data that would be used to define the optimal doses & dosing schedules of both drugs associated with the best efficacy/toxicity ratio by modeling/simulation. Methods: EVESOR is an open dose-escalation phase 1 trial assessing the combination of EVE and SOR in patients with multi-treated advanced solid tumors. Enrolled patients were allocated to 1 of the 4 arms: A) EVE 5 mg QD for 2 weeks followed by continuous EVE + SOR 200 mg BID; B) SOR 200 mg BID for 2 weeks followed by continuous EVE 5 mg QD + SOR; C) alternating EVE 5-10 mg QD with SOR 200-400 mg BID every week; D) continuous EVE 5-10 mg QD + SOR 200-400 mg BID for 3 days on-4 days off. Multiple tumor & blood pharmacokinetic (PK) and pharmacodynamic (PD) parameters were sampled at baseline and during treatment (Nanostring panels). The 1st endpoint was the RP2D of both drugs in each arm A+B; C; and D. Results: 43 patients were included from 2013 to 2019: arm A n= 7; arm B n= 7; arm C n= 16; arm D n = 13. Most of them had gynecological (25.6%), cholangiocarcinomas (23.2%), colorectal (14%), and breast cancers (11.6%). Dose escalations to EVE 10 mg QD and SOR 400 mg BID were possible in both arms C and D. Five dose-limiting toxicities (DLTs) were observed (1; 3; and 1 in arms B, C and D respectively). Dose reductions were needed in 40% patients, stabilizing at EVE 5 mg and SOR 200 mg BID for the majority of them (58%). The overall response rate was 7%, and the disease control rate (DCR) was 73%. No relationships between dose levels and efficacy were found. However, the intermittent dosing schedules (arms C and D) were associated with better DCR. The median progression-free survival (PFS) was 3.6 months (2.7; 6.3; 2.7; and 3.6 months in arms A, B, C and D). Longer PFS were observed with cholangiocarcinomas (9.8 months) and gynecological cancers (3.7 months). Baseline activation of RAS-RAF-ERK was associated with higher non-progression rates at 4 months (50% vs 10%, P=0.12) and longer PFS (4.2 vs 2.1 months, P = 0.016). Decreases in S6K and AKT phosphorylations were observed in 89% and 70% of patients, respectively, with no significant impact on efficacy. Conclusions: EVE 5 mg QD and SOR 200 mg BID combination is the RP2D in solid tumor patients, in both intermittent arms C & D. Intermittent dosing was associated with higher efficacy. Long responses were found in cholangiocarcinomas. Adequately designed multi-schedules phase 1 trials can help for drug development, and avoid abandon of effective targeted drug combinations. Modeling/simulation will be used to optimize dose & dosing schedules of EVE and SOR based on collected data, and then tested. Citation Format: Benoit You, Michel Tod, Lea Payen, Jonathan Lopez, Jerome Guitton, Pascal Rousset, Juliette Fontaine, Julien Peron, Denis Maillet, Sophie Tartas, Nathalie Bonnin, Veronique Trillet-Lenoir, Olivier Colomban, Diane Augu-Denechere, Gilles Freyer, Alicja Puszkiel. Clinical results of the multiparameter phase 1 trial EVESOR meant to optimize the doses and dosing schedules of the combination EVErolimus and SORafenib in solid tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT148.

International audience; BACKGROUND: Age-related immune dysfunction might impair the efficacy of immune checkpoint inhibitors (ICIs) in older patients. We aimed to evaluate the impact of age on clinical outcomes and tolerance of ICIs in a real-life setting. METHODS: All patients receiving a single-agent ICI (cytotoxic T-lymphocyte-associated protein 4 [CTLA-4] or programmed death(ligand)1 [PD(L)-1] inhibitors) for the standard treatment of a locally advanced or metastatic cancer were included in this retrospective multicentric series. The primary end-point was overall survival (OS). Progression-free survival (PFS) and immune-related adverse events (irAEs) were secondary end-points. The impact of age was assessed using the threshold of 70 years. RESULTS: A total of 410 patients were included, for 435 lines of treatment, including 150 lines (34%) given to patients aged 70 years or older. The primary tumour types were lung cancer (n = 304, 74%), melanoma (n = 79, 19%) and urologic cancer (n = 27, 7%). Most of the administered treatments were PD(L)-1 inhibitors (n = 356, 82%). Median follow-up reached 46 months in the CTLA-4 cohort, and 20 months in the PD(L)-1 cohort. In both treatment cohorts, age did not impact OS (respectively, HR = 0.82, 95% CI 0.5-1.4; log-rank P = 0.49 and HR = 0.9, 95% CI 0.7-1.1; log-rank P = 0.27) or PFS (HR = 0.7, 95% CI 0.4-1.1; log-rank P = 0.13 and HR = 0.9, 95% CI 0.7-1.1; log-rank P = 0.19). Grade 3-4 irAEs rates were not statistically different between older and younger patients (11% vs 12%, P = 0.87). CONCLUSION: In a large real-world series of patients treated by ICI monotherapy, the long-term clinical outcomes were not statistically different between older or younger patients, with no increased immune-related toxicity.

Management of non metastatic castrate resistant prostate cancer is challenging for clinicians due to the heterogeneity of the disease and to the scarce clinical data available in this setting. Recent results obtained with the new generation hormone therapies (NGHT) apalutamide and enzalutamide bring a new perspective for the treatment strategy. The authors present here a systematic review of the treatment options.

Introduction Malignant mesothelioma is a deadly disease that is strongly associated with asbestos exposure. Peritoneal mesotheliomas account for 10% of all the cases. BRCA1 associated protein 1 (BAP1) is a deubiquitinating hydrolase that plays a key role in various cellular processes. Germline and somatic inactivation of BRCA1 associated protein 1 gene ( BAP1 ) is frequent in pleural mesothelioma; however, little is known about its status in peritoneal mesothelioma. Methods Taking advantage of the extensive French National Network for the Diagnosis of Malignant Pleural Mesothelioma and Rare Peritoneal Tumors and the French National Network for the Treatment of Rare Peritoneal Surface Malignancies, we collected biological material and clinical and epidemiological data for 46 patients with peritoneal mesothelioma. The status of BAP1 was evaluated at the mutational and protein expression levels and combined with our previous data on copy number alterations assessed in the same samples. Results We detected mutations in 32% of the malignant peritoneal mesotheliomas analyzed. In addition, we have previously reported that copy number losses occurred in 42% of the samples included in this series. Overall, 73% of the malignant peritoneal mesotheliomas analyzed carried at least one inactivated BAP1 allele, but only 57% had a complete loss of its protein nuclear expression. Better overall survival was observed for patients with BAP1 mutations ( p = 0.04), protein expression loss ( p = 0.016), or at least one of these alterations ( p = 0.007) independently of tumor histological subtype, age, and sex. Conclusions As in pleural mesothelioma, inactivation of BAP1 is frequent in peritoneal mesotheliomas. We found that BAP1 protein nuclear expression is a good prognostic factor and a more reliable marker for the complete loss of BAP1 activity than mutation or copy number loss.

A prostate-specific antigen (PSA) flare occurs in about 15% of metastatic castration-resistant prostate cancer (mCRPC) patients receiving docetaxel. This flare has no standard definition. Its impact on treatment efficacy is unclear. We sought to evaluate the incidence and characteristics of PSA flare on cabazitaxel, and its impact on survival.Multicentre retrospective review of consecutive patients treated with cabazitaxel second-line chemotherapy for mCRPC. Collection of baseline characteristics, disease history and PSA levels before and during cabazitaxel therapy. Overall survival (OS) and radiological/clinical progression-free survival (PFS) for patient groups corresponding to different definitions of PSA flare estimated by the Kaplan-Meier method and compared using the log-rank test.Overall, 125 patients were included. Median PFS and OS were 6.5 and 13.3 months, respectively. Depending upon the definition used, flare incidence ranged from 8.3% to 30.6%. The flare lasted2.6 months. A PSA flare followed by a ⩾ 50% decrease was associated with a median PFS and OS of 11.2 and 25.2 months, respectively. Median PFS and OS for a ⩾ 30% rather than ⩾ 5 0% decrease were 10.4 and 16.5 months. These outcomes were not significantly different from those in patients with immediate PSA decreases of ⩾ 50% or ⩾ 30% from baseline, but were significantly better than in patients experiencing no PSA decrease (p = 0.006 and 0.015, respectively, for OS).The PSA response to cabazitaxel, with or without initial flare, was associated with a strong survival benefit. The taxane-induced flare during the first 12 weeks of therapy can be ignored when evaluating PSA response.

Background Age-related immune dysfunction might impair the efficacy of immune checkpoint inhibitors (ICIs) in older patients. We aimed to evaluate, in a real-life setting, if age was associated with long-term clinical outcomes and tolerance of ICIs. Methods All patients receiving an ICI monotherapy [CTLA-4 or PD(L)-1 inhibitors] for the standard treatment of a locally advanced or metastatic cancer were included in this retrospective multicentric series (three hospitals in the Hospices Civils de Lyon, France). The primary endpoint was overall survival (OS). Progression-free survival (PFS) and immune-related adverse events (irAEs) were secondary endpoints. The impact of age was assessed using the threshold of 70 years. Results Between January 2007 and October 2017, 410 patients were included in this series, for a total of 435 lines of treatment. One hundred and fifty lines (34%) were received by patients of 70 years or older. They were administered for a lung cancer (n = 304, 74%), a melanoma (n = 79, 19%) or a urologic cancer (n = 27, 7%). Most of the administered treatments were PD(L)-1 inhibitors (n = 356, 82%). Mean follow-up duration starting at treatment initiation was 46 months in the CTLA-4 cohort, and 20 months in the PD(L)-1 cohort. For both CTLA-4 inhibitors and PD(L)-1 inhibitors, there was no statistical association between age and OS (respectively, HR 0.8, 95% CI: 0.5-1.4; log-rank P = 0.49 and HR = 0.9, 95% CI: 0.7-1.1; Log-rank P = 0.27) or PFS (respectively, HR = 0.7, 95% CI: 0.4-1.1; log-rank P = 0.13 or HR = 0.9, 95% CI: 0.7-1.1; Log-rank P = 0.19) in univariate analysis, and after adjusting on prognosis covariates. Older patients did not have more grade 3-4 irAEs (11% versus 12%, P = 0.87). Conclusions In this large real-world series, the long-term clinical outcomes were not statistically different between patients older or younger than 70 years who had received ICIs as a single agent in standard practice for an advanced solid tumor. Older patients did not have more severe immune-related adverse events. These data suggest that the use of ICI monotherapy for older patients may be safe with no specific monitoring. Legal entity responsible for the study Julien Peron. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

3060 Background: The determination of the optimal biological dose (OBD) defined as the lowest safe dose associated with biological efficacy, appears to be a promising endpoint for defining the recommended phase 2 trial dose (RP2D) of novel oncologic targeted therapies in early-phase clinical trials. However, the clinical relevance of OBD is still unknown. We conducted a review to assess if the OBDs of molecular targeted therapies defined during early phase trials were useful during subsequent drug development and for oncologic drug approvals. Methods: A systematic review was conducted to identify all the molecular targeted therapies approved by FDA in solid and hematological malignancies, and for which early phase trials defined OBDs. The publications of efficacy trials leading to the first FDA approvals were reviewed, as were the FDA approved doses and dosing schedules, which were compared to OBDs found in the early phase trials. Results: OBDs were reported in the early phase trial articles of 39.5% (32/81) FDA approved targeted therapies from 1999 to 2017 (19 small molecules and 13 monoclonal antibodies (mAbs)). The maximum tolerated doses (MTD) had not been reached for 59.4% (19/32) of these drugs. When both MTD and OBD had been defined, OBD were lower than MTD in 84.6% of cases, and equal for the others. The OBDs were chosen as the RP2Ds for 56.3% of the molecules. In that case, the final FDA approved doses were consistent with the OBDs for 83.3% of the drugs. These percentages did not differ in between small molecules and mAbs. OBDs mainly relied on indirect effects on the involved signaling pathway elements for small molecules (11/19, 57.9%), and on involved receptor occupancies for mAbs (6/13, 46.2%). In total, 23.5% of all FDA approved molecular targeted therapies were approved at their OBDs. Conclusions: Although still poorly investigated, OBD may represent a relevant complementary endpoint in in early phase trials of novel anti-cancer targeted therapies, as OBDs are selected as the final FDA approved doses in 83.3 % of cases when chosen as the RP2Ds, which is much higher than the previously reported 58.0 % when MTDs are chosen as the RP2Ds (Fontes-Jardim et al. JNCI 2015).

International audience; Visible and near-infrared spectral range of light can be used for estimating the optical properties of a biological tissue in a non-invasive way starting from its response to an external light stimulus. A forward model based on the time-dependent radiative transfer equation, that accurately describes light propagation through such media, is considered and solved with a finite-volume method for the discretization of the spatial domain. Results in terms of fluence and of reflectance at the illuminated transparent or semi-transparent wall for liver and skin tissues subjected to a collimated short-pulsed near-infrared laser are presented and discussed. A sensitivity analysis of the reflectance in the time domain to the four optical parameters of the model shows that only two of them can be estimated: the asymmetry factor of the Henyey–Greenstein phase function as well as either the refractive index or the scattering coefficient of the tissue. The reduced model can be used to invert the experimental reflectance measured assuming the signal over noise ratio of the detector known in the corresponding non-invasive detection technique.

Purpose The Consolidated Standards of Reporting Trials (CONSORT) guidance was extended in 2004 to provide a set of 10 specific and comprehensive guidelines regarding adverse event (AE) reporting in randomized clinical trials (RCTs). Limited data exist regarding adherence to these guidelines in publications of oncology RCTs. Methods All phase III RCTs published between 2007 and 2011 were reviewed using a 16-point AE reporting quality score (AERQS) based on the 2004 CONSORT extension. Multivariable linear regression was used to identify features associated with improved reporting quality. Results A total of 325 RCTs were reviewed. The mean AERQS was 10.1 on a 16-point scale. The most common items that were poorly reported were the methodology of AE collection (adequately reported in only 10% of studies), the description of AE characteristics leading to withdrawals (15%), and whether AEs are attributed to trial interventions (38%). Even when reported, the methods of AE collection and analysis were highly heterogeneous. The multivariable regression model revealed that industry funding, intercontinental trials, and trials in the metastatic setting were predictors of higher AERQS. The quality of AE reporting did not improve significantly over time and was not better among articles published in journals with a high impact factor. Conclusion Our findings show that some methodologic aspects of AE collection and analysis were poorly reported. Given the importance of AEs in evaluating new treatments, authors should be encouraged to adhere to the 2004 CONSORT guidelines regarding AE reporting.

Aim: This novel multiparameter Phase I study aimed to optimize doses/dosing schedules of everolimus and sorafenib drug combination, based on modeling/simulation (NCT01932177). Patients & methods: About 26 patients with solid tumors were treated in four different dosing schedules. Everolimus once daily + sorafenib twice daily were given continuously in arms A and B, and intermittently in arms C (alternating every other week) and D (everolimus continuous and sorafenib 3 days on/4 days off). Results: Continuous schedules exhibited higher toxicity risks than intermittent schedules (64.1 vs 35.9%; p < 0.0001), and trends for lower disease control rates (80 vs 100%). No significant pharmacokinetic interaction was identified. Conclusion: Feasibility of EVESOR trial is demonstrated. Intermittent schedules might provide better tolerance and efficacy than continuous schedules.

An inverse problem is considered here that consists in the reconstruction of heat source maps from the measurement of 2D temperature fields. The endorsed application concerns the thermomechanical characterization of materials submitted to mechanical loads. An infrared camera is used to record the temperature evolutions resulting from reversible or more usually irreversible heat dissipation. An algorithm is presented and checked theoretically on simulated data. It relies on a formulation in terms of a constrained optimization problem. One constraint imposes the observance of the heat governing equation. The second constraint is a penalty term of Tikhonov type. A discretization of the equations resulting from the minimization conditions yield a linear matrix form. The main problem concerns the conditioning of the sparse matrix so obtained, which is seriously damaged if one tries to get a very fine spatial resolution for the source. The strategy used for optimal regularization is obtained in two steps. First, prior information is obtained from experiments in a light inversion procedure. Second, this information is used for efficient regularization. This algorithm has the advantage of being easy to implement and independent from hypothesis on boundary conditions. The L-curve criterion is shown to produce good results and a robust processing for noisy data.

International audience; BACKGROUND: Randomised controlled trials (RCTs) represent a major source of information on treatment-related adverse events (AEs). In this study, we reviewed the use and the reporting methods of aggregated-AEs (A-AEs) outcomes in RCTs reports published in oncology and compared that to the expectations of European Organisation for Research and Treatment of Cancer (EORTC) membership. METHODS: RCTs reports published between 2007 and 2011 were reviewed regarding the reporting of A-AEs-outcomes. A-AEs were defined as summary outcome combining several related AEs, usually grouped by organ system e.g. cardiac-AEs, dermatologic-AEs. Trial characteristics associated with the use of A-AEs outcomes were investigated. The expectation of EORTC members concerning A-AEs utilisation was queried through a survey. RESULTS: Among 325 RCTs published between 2007 and 2011, 94 (29%) included one or more A-AE outcomes. A clear description of the nature of AEs included in such aggregations was provided in 19 articles (20%). No description of A-AEs was conversely provided in the other 75 articles (80%). The most commonly used A-AEs-outcomes were dermatologic-AEs (45%) and cardiac-AEs (33%). In multivariate analysis, the use of A-AEs outcomes was more frequent when trials were conducted in Europe (p = 0.038) and in trials performed on colon/rectal cancers (p = 0.016). Finally, there is no consensus of EORTC members regarding the utilisation of A-AEs but a majority of them (88%) felt that a clear description of A-AEs should systematically be reported. CONCLUSIONS: The use of A-AEs is infrequent in oncology RCT manuscripts although their use is accepted by most clinicians. However, a clear definition of A-AEs is strongly recommended if they are to be used in order to avoid a loss of important details about drug toxicities that is useful to clinicians

International audience; BACKGROUND: Determination of drug safety and tolerability is usually based on the frequency of certain key adverse events (AEs) rather than the frequency of all-grade toxicities. We assessed the reporting of key AEs in oncology randomized, controlled trials (RCTs) and compared that with the expectations of the European Organization for Research and Treatment of Cancer (EORTC) membership. MATERIALS AND METHODS: RCTs reports published between 2007 and 2011 were reviewed regarding the reporting of key AEs, namely: grade 3/4 AEs, grade 5 AEs, and AEs resulting in study withdrawal or in dose reduction. Study characteristics associated with better reporting of key AEs were investigated. Finally, a survey was conducted among the EORTC membership to determine their expectations on key AEs reporting. RESULTS: Although the frequency of grade 3/4 was reported in most reports (96%), only 17% of them described the reporting threshold above which grade 3/4 AEs were included for reporting, raising the possibility that important but less frequent grade 3/4 AEs might be underreported. Frequency and nature of grade 5 AEs were adequately reported in 161 (50%) of manuscripts; AEs leading to study withdrawal in 61 manuscripts (19%); and AEs leading to dose reduction in 43 manuscripts (13%). In contrast, most EORTC members expected a comprehensive reporting of grade 5 AEs (96% of EORTC member's responses), AEs leading to study withdrawal (86%) and AEs leading to dose reduction (70%). In multivariate analysis, frequencies of grade 5 AEs were less frequently reported in European trials (P = 0.004). Frequencies of AEs leading to withdrawals were more frequently reported in trials funded by industry (P = 0.005) and in trials including patients with breast or urological cancers (P = 0.006). CONCLUSIONS: These findings suggest that current practice of key AEs reporting remains highly variable and sometimes inadequate in oncology RCTs reports. Current standards for safety reporting in RCTs should be revised to emphasize the importance of key AEs reporting

The extension of the heat pulse method, commonly used for the measurement of the diffusivity of homogeneous isotropic materials, to the characterization of multiplayer structures that can be found in electronic boards, for example, is examined. Both models and experimental estimations of thermophysical property measurement are presented for the diffusivity in the thickness direction, for interface contact resistance (glue) characterization, and for deposits on substrates. A strong emphasis is placed on sensitivity analysis and the type of thermal parameter that can be reached in practice for a given experiment. Estimation of the in-plane thermal diffusivity of possible anisotropic flat-plate samples through a nonhomogeneous pulse excitation and infrared camera measurements are presented.

A transient method using the Laplace transform for estimation of the in-plane thermal diffusivity of low conductive materials is presented. The temperature field of the sample is measured by infrared thermography. The main interest of the technique proposed here is to not require a knowledge of the stimulation and boundary conditions by using two reference temperature profiles. The parameter estimation is implemented in the time domain by an inverse technique using numerical Laplace inversion and convolution products. A sensitivity study has been carried out to optimize the choice of the two reference profiles. The effect of a space varying heat transfer coefficient on the estimated values of the unknown parameters has also been evaluated. Finally, the apparatus is described and experimental results obtained for a low conductive material like a vitroceramic are shown.

Mathematical modeling is presented of the combined conductive and radiative heat transfer occurring in a semitransparent material (STM) subjected to a periodic heat flux. The models rely on the quadrupole method, which is a very powerful tool to obtain analytical solutions in the Fourier or Laplace domain. Photoacoustic or photothermal radiometry techniques are reviewed. Two groups of methods are discussed depending on whether the sample has natural or opaque interfaces to simulate radiative exchanges with the surroundings. The metrological problem of measuring the phonic thermal diffusivity of semitransparent materials is investigated. Theoretical simulations are given. They explain some typical features of the phase-lag signal of temperature responses. Experimental measurements on pure silica validate the results and prove that these methods are efficient for the thermal characterization of STM.

The aim of this theoretical and experimental study is to provide a complete methodology to estimate the intrinsic diffusivity of semi-transparent media from flash method experiments. A semi-analytical model describes the coupled conductive–radiative transient heat transfer in a slab. The relevance of the model used for the inversion is then investigated. Experimental results are presented for several semi-transparent samples: float glass, SiO 2 and ZnSe. Measurements of rear face temperature are obtained by optical way (infrared detection) for a wide temperature range (293–700 K), for several radiation boundary conditions (black or gold coatings). The results are compared with those obtained through an other set-up and an other experimental procedure.

Background The Consolidated Standards of Reporting Trials (CONSORT) guidance was extended in 2013 to provide a set of specific recommendations regarding patient-reported outcomes (PROs) reporting in randomized clinical trials (RCTs). There is limited data regarding how well current publications of oncology RCTs report PROs if assessed using these guidelines. Design All phase III medical oncology RCTs published between 2007 and 2011 were reviewed according to the 2013 PROs CONSORT recommendations and an 11-point PROs reporting quality score (PRORQS) was defined based on the criteria. Results The majority of trials did not report on PROs at all (201 of 325; 62%). Of the remaining 124 trials, the mean PRORQS score was 5.0 on an 11-point scale. The items related to methods of PROs collection and analysis were poorly reported (Description of the prespecified PRO hypothesis: 26% of RCTs; methods for PRO data collection (paper, telephone, electronic, other): 16%; statistical approaches for managing missing data: 37%). The only factor significantly associated with improved PROs reporting was where PROs reporting was the subject of a dedicated secondary manuscript, as was the case in 36 of the 124 (29%) of RCTs. Conclusion Despite their clinical relevance, our findings show that some aspects of PROs reporting may greatly be improved, especially critical methodological aspects of PROs collection and analysis. The exceptions were where PROs were described in PROs-specific secondary publication. Use of the 2013 PROs CONSORT extensions should be encouraged and their effects on PROs reporting subsequently reassessed.

Transient radiative and conductive heat transfer in an absorbing, emitting and anisotropically scattering gray slab is investigated. The medium is confined within parallel walls and is excited by a heat pulse stimulation on the front face. The phase function corresponds to a second-degree anisotropic scattering and includes isotropic, linearly anisotropic and Rayleigh modes of scattering. The semi-analytical approach, based on the kernel substitution consists in obtaining a differential equation for the temperature field instead of the natural integro-differential energy equation. A matrix formulation of the solution is proposed. It allows very small resulting computation times and permits to investigate the effects of anisotropic scattering on the thermal behaviour of the semi-transparent medium.