1b) Be sure to check out (and earn even MORE πCE/#CME credit from my colleague @PatelOncology 's introduction to contemporary #ES_SCLC management at https://t.co/hqEQbEqvBg.
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
We strive to keep our π« med colleagues up to date on oncology issues!
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/0EkFYk4TZx pic.twitter.com/G4FGuBgSzy
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
4b) @ESMO guidelines π https://t.co/aUvjNS1Pcb
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
recommend CT-scan and brain imaging. 18-FDG-PET is optional unless bone metastases are suspected. pic.twitter.com/CMOFsFst9d
5a) What is the current standard-of-care for 1L tx of pts with ES-SCLC?
— pulmmed_ce (@Pulmmed_CE) February 8, 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.
— pulmmed_ce (@Pulmmed_CE) February 8, 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.
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
5g) Therefore, @ESMO guidelines π https://t.co/aUvjNS1Pcb state that #cisplatin can be substituted by #carboplatin.
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
6b) The answer is 4 cycles, then maintenance w/ immunotherapy
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
All guidelines primarily recommend immune checkpoint inhibitors atezolizumab or durvalumab to be combined w/ chemotherapy w/ platinum and etoposide upfront for 4 cycles. @NCCN guidelines π https://t.co/8LDqdMhluz
7) These recs are based on 2 landmark phase III #RCTs that demonstrated an #OS benefit with combination of chemotherapy and immunotherapy: #IMpower_133 π https://t.co/SER3XNl2r7
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
and #CASPIAN π https://t.co/b9CwOV2lWd
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/IYHgPIvoR9
— pulmmed_ce (@Pulmmed_CE) February 8, 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/AXNHvBJ8D2
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
11) Another randomized trial, conducted in Asia, showed a similar benefit with other anti-#PD1 agents in trials with comparable designs: #ASTRUM_005 with #serplulimab https://t.co/RqLbS6f7g1 pic.twitter.com/RIulgszUTc
— pulmmed_ce (@Pulmmed_CE) February 8, 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.
— pulmmed_ce (@Pulmmed_CE) February 8, 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. π https://t.co/l5ebGc2TU9
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
16b) @NCCN guidelines π https://t.co/8LDqdMhluz 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.
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
17a) Is there any predictor for the efficacy of immunotherapy that would help to select patients and identify the long-term responders?
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
17c) From #CASPIAN, an analysis was done in long-term responders β₯12 months π https://t.co/TC9oGeFPxz pic.twitter.com/gFFZQRb7To
— pulmmed_ce (@Pulmmed_CE) February 8, 2023
18) OK, need a break? Lots of info shared already, but please return TOMORROW for more on management of #ES_SCLC!
— pulmmed_ce (@Pulmmed_CE) February 8, 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).
— pulmmed_ce (@Pulmmed_CE) February 9, 2023
ππ https://t.co/6hlsDsneR9
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
— pulmmed_ce (@Pulmmed_CE) February 9, 2023
π https://t.co/s7xv9QH7a3
π https://t.co/AkCWCdClRm pic.twitter.com/ffExqzejME
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.
— pulmmed_ce (@Pulmmed_CE) February 9, 2023
π https://t.co/TjuhUv4R9X
22d) @NCCN guidelines π https://t.co/8LDqdMhluz recommend MRI surveillance and consider #PCI as an option pic.twitter.com/C2qBZhTnvT
— pulmmed_ce (@Pulmmed_CE) February 9, 2023
23b) Per @NCCN guidelines π https://t.co/8LDqdMhluz and @ESMO guidelines π https://t.co/aUvjNS1Pcb, consider thoracic RT in patients with good response to #ES_SCLC pic.twitter.com/1OKnVrJ8ea
— pulmmed_ce (@Pulmmed_CE) February 9, 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%).
— pulmmed_ce (@Pulmmed_CE) February 9, 2023
24d) Note that the cut-off is 6β£months per @NCCN guidelines: π https://t.co/8LDqdMhluz
— pulmmed_ce (@Pulmmed_CE) February 9, 2023
…
but 3β£ months per @ESMO guidelines https://t.co/aUvjNS1Pcb
25b) In platinum-refractory tumors or after rechallenge in sensitive tumors, multiple options are listed in the @NCCN guidelines π https://t.co/8LDqdMhluz and @ESMO guidelines π https://t.co/aUvjNS1Pcb pic.twitter.com/gugzKUYR7v
— pulmmed_ce (@Pulmmed_CE) February 9, 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.
— pulmmed_ce (@Pulmmed_CE) February 9, 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/YIjU6KCupe pic.twitter.com/3dyjfX75Vz
— pulmmed_ce (@Pulmmed_CE) February 9, 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.
— pulmmed_ce (@Pulmmed_CE) February 9, 2023
28c) Adverse events include #cytokine_release_syndrome, neurologic events, and #neutropenia. pic.twitter.com/f0E6lRRgV2
— pulmmed_ce (@Pulmmed_CE) February 9, 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/3yt7fz8KBZ
— pulmmed_ce (@Pulmmed_CE) February 9, 2023
30b)
— pulmmed_ce (@Pulmmed_CE) February 9, 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/B51azskI6f for your certificate! I am @nicogirardcurie. FOLLOW US!
— pulmmed_ce (@Pulmmed_CE) February 9, 2023