1b) Our expert author is Nicolas Girard @nicogirardcurie, #lungcancer & rare #thoracic #tumors specialist from Institut Curie, Paris @institut_curie. π«π· Follow us on @onc_ce for the latest updates in #oncology and πCE/#CME! Prior programs for credit at https://t.co/3Nl35CTy8T
β @onc_ce (@onc_ce) January 24, 2023
3) This program is supported by an educational grant from AstraZeneca and is intended for #healthcare providers. Statement of accreditation and faculty disclosures are at https://t.co/8oShcATWla pic.twitter.com/b2gPdAkWCd
β @onc_ce (@onc_ce) January 24, 2023
4b) @ESMO guidelines πhttps://t.co/5anI2lUcs4
β @onc_ce (@onc_ce) January 24, 2023
recommend CT-scan and brain imaging. 18-FDG-PET is optional unless bone metastases are suspected. pic.twitter.com/P4Zgu2QIeJ
5a) What is the current standard-of-care for 1L tx of pts with ES-SCLC?
β @onc_ce (@onc_ce) January 24, 2023
a. chemotherapy w/platinum & #etoposide
b. chemotherapy w/platinum & etoposide combined w/ immune checkpoint inhibitor
c. chemotherapy w/platinum & etoposide followed by immune checkpoint inhibitor
5c) All recommend immune checkpoint inhibitors #atezolizumab or #durvalumab to be combined with chemotherapy with platinum and #etoposide upfront, with a high level of evidence and recommendation.
β @onc_ce (@onc_ce) January 24, 2023
βSo now: is your preference for carboplatine or cisplatine?
5e) From this meta-analysis, it seems that in younger patients (<70 years), the outcome might be moderately better with cisplatin, although these subgroup analyses were exploratory.
β @onc_ce (@onc_ce) January 24, 2023
5g) Therefore, @ESMO guidelines πhttps://t.co/5anI2lUcs4 state that #cisplatin can be substituted by #carboplatin.
β @onc_ce (@onc_ce) January 24, 2023
6b) The answer is 4 cycles, then maintenance w/ immunotherapy
β @onc_ce (@onc_ce) January 24, 2023
All guidelines primarily recommend immune checkpoint inhibitors atezolizumab or durvalumab to be combined w/ chemotherapy with platinum & etoposide upfront for 4 cycles. @NCCN guidelines πhttps://t.co/i8NR5ALEyv pic.twitter.com/IpB1BoUJC9
7) These recs are based on 2 landmark phase III #RCTs that demonstrated an #OS benefit with combination of chemotherapy and immunotherapy: #IMpower_133 πhttps://t.co/pCir6uYXtU
β @onc_ce (@onc_ce) January 24, 2023
and #CASPIAN πhttps://t.co/fp17ezCPlw
8b) In IMpower 133, OS benefit was observed with atezolizumab, with median OS of 12.3 months vs. 10.3 months with placebo. pic.twitter.com/tBwaB0XX44
β @onc_ce (@onc_ce) January 24, 2023
9b) In CASPIAN, OS benefit was observed with median OS of 10.5 in the control arm and 12.9 months in the durvalumab arm. Durvalumab led to sustained benefit with 3 year OS rate of 17.6% vs. 5.8% in the control arm. pic.twitter.com/2yLi1TcTLe
β @onc_ce (@onc_ce) January 24, 2023
11) Another randomized trial, conducted in Asia, showed a similar benefit with other anti-#PD1 agents in trials with comparable desgins: #ASTRUM_005 with #serplulimab https://t.co/RWnmWfaGfC pic.twitter.com/WIpX508bC9
β @onc_ce (@onc_ce) January 24, 2023
13) In clinical practice, patients may not be amenable upfront to #immunotherapy, because of #brain_metastases, poor PS, or need for high steroid doses. #Chemotherapy alone may then be delivered.
β @onc_ce (@onc_ce) January 24, 2023
15) Meanwhile, we must initiate immunotherapy during chemotherapy. #CheckMate_451 failed to show any benefit of #ICIs nivolumab+/-ipilimumab as switch maintenance when initiated in non-progressive #SCLC after 4 cycles of platinum & etoposide. πhttps://t.co/udCRHyfznE
β @onc_ce (@onc_ce) January 24, 2023
16b) @NCCN guidelines πhttps://t.co/i8NR5ALEyv recommend for #ES_SCLC that during systemic therapy, response assessment by chest/abdomen/pelvis CT with contrast should occur after every 2β3 cycles of systemic therapy and at completion of therapy.
β @onc_ce (@onc_ce) January 24, 2023
17a) Is there any predictor for the efficacy of immunotherapy that would help to select patients and identify the long-term responders?
β @onc_ce (@onc_ce) January 24, 2023
a. PD-L1 expression
b. Tumor Mutation Burden
c. LDH
d. no
17c) From #CASPIAN, an analysis was done in long-term responders β₯12 months πhttps://t.co/QsDl79uWZe pic.twitter.com/VhvKG4CpNc
β @onc_ce (@onc_ce) January 24, 2023
18) OK, need a break? Lots of info shared already, but please return TOMORROW for more on management of #ES_SCLC!
β @onc_ce (@onc_ce) January 24, 2023
π@PatelOncology @StephenVLiu @oncologician @LealTiciana @chulkimMD @Tony_Calles @FawziAbuRous @NickMarcouxMD @NReguart @ADesaiMD#LCSM #FOAMed
20a) A molecular classification of #SCLC has emerged, based on #RNA-Sequencing signature, and defining 4 groups of tumors, referred as to #ASCL1 (SCLC-A), #NEUROD1 (SCLC-N), #POU2F3 (SCLC-P), #Inflamed (SCLC-I), and possibly #YAP1 (SCLC-Y).
— @onc_ce (@onc_ce) January 25, 2023
ππhttps://t.co/S93zzlPeRW
21) Emerging evidence suggest that the #SCLC_I is consistently associated with more prolonged survival with chemotherapy and immune checkpoint inhibitor, based on data from #Impower_133 and #CASPIAN
— @onc_ce (@onc_ce) January 25, 2023
πhttps://t.co/TiKmO2q3Dw
πhttps://t.co/zobnRPpSIM pic.twitter.com/9C0qvOnz4z
22b) In patients with #ES_SCLC that has responded to systemic therapy, #PCI decreases brain metastases. A randomized trial conducted by the #EORTC found improved overall survival with PCI.
— @onc_ce (@onc_ce) January 25, 2023
πhttps://t.co/4yiUKieJIY
22d) @NCCN guidelines πhttps://t.co/i8NR5ALEyv recommend MRI surveillance and consider #PCI as an option pic.twitter.com/RMHKaeyCYe
— @onc_ce (@onc_ce) January 25, 2023
23b) Per @NCCN guidelines πhttps://t.co/i8NR5ALEyv and @ESMO guidelines πhttps://t.co/5anI2lUcs4, consider thoracic RT in patients with good response to #ES_SCLC pic.twitter.com/GO4UC4naM3
— @onc_ce (@onc_ce) January 25, 2023
24b) Likelihood of response is highly dependent on the time from initial therapy to relapse. If this interval is 6 months or less (refractory or resistant disease), response to most agents or regimens is poor (β€10%).
— @onc_ce (@onc_ce) January 25, 2023
24d) Note that the cut-off is 6β£months per @NCCN guidelines: πhttps://t.co/i8NR5ALEyv
— @onc_ce (@onc_ce) January 25, 2023
…
but 3β£ months per @ESMO guidelines https://t.co/5anI2lUcs4
25b) In platinum-refractory tumors or after rechallenge in sensitive tumors, multiple options are listed in the @NCCN guidelines πhttps://t.co/i8NR5ALEyv and @ESMO guidelines πhttps://t.co/5anI2lUcs4 pic.twitter.com/4uvZ8OGkxm
— @onc_ce (@onc_ce) January 25, 2023
26b) Oral administration is usually preferred at a dose of 2.3 mg/m2/d on days 1 – 5 every 21 days according to marrow recovery.
— @onc_ce (@onc_ce) January 25, 2023
The @NCCN #SCLC Panel recommends topotecan as a preferred subsequent therapy option for pts with SCLC who have relapsed 6 months or less after therapy.
27b) However, in the randomized #ATLANTIS trial, #lurbinectedin combined with #doxorubicin did not show a significantly better survival than #topotecan. See https://t.co/imbbgWz1KO pic.twitter.com/jQlcUWRf3E
— @onc_ce (@onc_ce) January 25, 2023
28a) A promising strategy is #tarlatamab, a bispecific T-cell engager agent targeting #DLL_3, a cell surface receptor of #SCLC cell and #CD3, that reported 23% overall response rate in the #DELLPHI_300 phase I trial presented at #WCLC 2022 meeting.
— @onc_ce (@onc_ce) January 25, 2023
28c) Adverse events include #cytokine_release_syndrome, neurologic events, and #neutropenia. pic.twitter.com/ZZmZlW9KyU
— @onc_ce (@onc_ce) January 25, 2023
29) Another strategy assessed in clinical trials is B7 homologue 3 (#B7_H3) targeting. In a phase I study, DS-7300 (B7-H3 deruxtecan Antibody Drug Conjugate #ADC) showed promising effect in patients with relapsed/refractory SCLC. These data were presented at #ESMO22 meeting. pic.twitter.com/nuYxO0Xppu
— @onc_ce (@onc_ce) January 25, 2023
30b)
— @onc_ce (@onc_ce) January 25, 2023
π« Second-line consists of chemotherapy rechallenge in platinum-sensitive cases, or #topotecan/#lurbinectedin as preferred options in platinum-resistant cases
31) And you made it! You just earned 0.75h πCE/#CME from your ONLY source for #accredited serialized #tweetorials. π±οΈ to https://t.co/jY5BSN94Ae for your certificate! I am @nicogirardcurie. FOLLOW US!
— @onc_ce (@onc_ce) January 25, 2023